From 9cba9125ad72f5a787dd8458aacfcbbbe5f8f668 Mon Sep 17 00:00:00 2001 From: Pablo Riesgo-Ferreiro Date: Thu, 9 Feb 2023 09:10:56 +0000 Subject: [PATCH 01/83] extend support for python 3.8 bugfix versions --- neofox/__init__.py | 2 +- setup.py | 2 +- 2 files changed, 2 insertions(+), 2 deletions(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index 1d64c073..c08261bd 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b1" +VERSION = "1.1.0b2" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" diff --git a/setup.py b/setup.py index ea4290f5..7643d65f 100755 --- a/setup.py +++ b/setup.py @@ -66,6 +66,6 @@ "License :: OSI Approved :: GNU General Public License v3 (GPLv3)", "Operating System :: Unix" ], - python_requires='>=3.6,<=3.8.12', + python_requires='>=3.6,<3.9', license='GPLv3', ) From bdd149b7624cc92f40cc299d68c5eeebc09052cb Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Thu, 9 Feb 2023 15:33:49 +0100 Subject: [PATCH 02/83] 1.1.0b3 --- neofox/__init__.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index c08261bd..ca51d04c 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b2" +VERSION = "1.1.0b3" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" From c47c6951774e06563ffd6f5215d3effa273d929a Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Thu, 9 Feb 2023 15:37:19 +0100 Subject: [PATCH 03/83] renaming MHCI --- .../netmhcpan/combine_netmhcpan_pred_multiple_binders.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/neofox/MHC_predictors/netmhcpan/combine_netmhcpan_pred_multiple_binders.py b/neofox/MHC_predictors/netmhcpan/combine_netmhcpan_pred_multiple_binders.py index a6da0863..3d388757 100755 --- a/neofox/MHC_predictors/netmhcpan/combine_netmhcpan_pred_multiple_binders.py +++ b/neofox/MHC_predictors/netmhcpan/combine_netmhcpan_pred_multiple_binders.py @@ -190,7 +190,7 @@ def get_annotations(self) -> List[Annotation]: if self.best_epitope_by_rank: annotations.extend([ AnnotationFactory.build_annotation( - value=self.best_epitope_by_rank.rank_mutated, name="NetMHCpan_MHCI_bestRank_rank" + value=self.best_epitope_by_rank.rank_mutated, name="NetMHCpan_bestRank_rank" ), AnnotationFactory.build_annotation( value=self.best_epitope_by_rank.mutated_peptide, From c268f370a7d54bd633243c1c4eeecdbab20e73f6 Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Tue, 14 Feb 2023 15:34:53 +0100 Subject: [PATCH 04/83] checking if patients exist in the patient data --- neofox/__init__.py | 2 +- neofox/command_line.py | 6 ++++++ 2 files changed, 7 insertions(+), 1 deletion(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index ca51d04c..31dbbee8 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b3" +VERSION = "1.1.0b4" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" diff --git a/neofox/command_line.py b/neofox/command_line.py index 79f6795c..b9e313e5 100755 --- a/neofox/command_line.py +++ b/neofox/command_line.py @@ -213,6 +213,12 @@ def _read_data(input_file, patients_data, mhc_database: MhcDatabase) -> Tuple[Li else: raise ValueError('Not supported input file extension: {}'.format(input_file)) + ### Van -- check if patient candidates exist in the patient data file + neoantigens_patient_ids = set(i['patientIdentifier'] for i in neoantigens) + patient_ids = set(j['identifier'] for j in patients) + if neoantigens_patient_ids.difference(patient_ids) > 0: + raise ValueError('%s patient candidate does not exist in the patient data file.' % patient) + return neoantigens, patients From ff5ce16e1c3db023c03e695f407b8f22c1893974 Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Tue, 21 Feb 2023 16:07:51 +0100 Subject: [PATCH 05/83] 257-fix error in command_line --- neofox/__init__.py | 2 +- neofox/command_line.py | 2 +- 2 files changed, 2 insertions(+), 2 deletions(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index 31dbbee8..26f87959 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b4" +VERSION = "1.1.0b5" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" diff --git a/neofox/command_line.py b/neofox/command_line.py index b9e313e5..204827e2 100755 --- a/neofox/command_line.py +++ b/neofox/command_line.py @@ -217,7 +217,7 @@ def _read_data(input_file, patients_data, mhc_database: MhcDatabase) -> Tuple[Li neoantigens_patient_ids = set(i['patientIdentifier'] for i in neoantigens) patient_ids = set(j['identifier'] for j in patients) if neoantigens_patient_ids.difference(patient_ids) > 0: - raise ValueError('%s patient candidate does not exist in the patient data file.' % patient) + raise ValueError('%s patient candidate does not exist in the patient data file.' % neoantigens_patient_ids) return neoantigens, patients From 25409f86a85cf595a9acccd2d14f5c95170c1892 Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Thu, 23 Feb 2023 10:50:26 +0100 Subject: [PATCH 06/83] update regex of IEDB allele names --- neofox/__init__.py | 2 +- neofox/model/mhc_parser.py | 2 +- 2 files changed, 2 insertions(+), 2 deletions(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index 26f87959..ebb9e254 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b5" +VERSION = "1.1.0b6" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" diff --git a/neofox/model/mhc_parser.py b/neofox/model/mhc_parser.py index 1d3151e2..b6082516 100644 --- a/neofox/model/mhc_parser.py +++ b/neofox/model/mhc_parser.py @@ -38,7 +38,7 @@ ) HLA_DR_MOLECULE_PATTERN = re.compile(r"(?:HLA-)?(DRB1[\*|_]?[0-9]{2,}[:|_]?[0-9]{2,})") -H2_ALLELE_PATTERN = re.compile(r"(H2K|H2D|H2L|H2A|H2E)([a-z][0-9]?)") +H2_ALLELE_PATTERN = re.compile(r"(H2-?[KDLAE])([a-z][0-9]?)") H2_NETMHCPAN_ALLELE_PATTERN = re.compile(r"H-2-I?(K|D|L|A|E)([a-z][0-9]?)") H2_MOLECULE_PATTERN = re.compile(r"(H2A|H2E)([a-z][0-9]?)") From 9f55669818835b7814a7d9a32a0179e4a703c8ce Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Tue, 28 Feb 2023 21:30:00 +0100 Subject: [PATCH 07/83] remove and edit name of some columns --- docs/source/03_02_output_data.md | 181 +++++++++++++++---------------- neofox/__init__.py | 2 +- 2 files changed, 91 insertions(+), 92 deletions(-) diff --git a/docs/source/03_02_output_data.md b/docs/source/03_02_output_data.md index 6d612cc2..29447506 100755 --- a/docs/source/03_02_output_data.md +++ b/docs/source/03_02_output_data.md @@ -12,97 +12,96 @@ The following table describes each of the annotations in the output: **TABLE 1** -| Column name | Description | Feature group/ Paper | -|----------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------| -| dnaVariantAlleleFrequency | the variant allele frequency calculated from the DNA | - | -| mutation.mutatedXmer | the long mutated amino acid sequence | - | -| mutation.wildTypeXmer | the long non-mutated amino acid sequence. This field shal be empty for alternative neoantigen classes | - | -| patientIdentifier | the patient identifier | - | -| rnaExpression | the RNA expression. If expression was imputed, this will will be `imputedGeneExpression` | expression | -| imputedGeneExpression | median gene expression in the TCGA cohort of the tumor entity provided in the patient file. | expression | -| rnaVariantAlleleFrequency | the variant allele frequency calculated from the RNA | - | -| gene | the HGNC gene symbol | - | -| Expression_mutated_transcript | transcript expression normalized by the variant allele frequency of the mutation | expression | -| mutation_not_found_in_proteome | indicates if mutated amino acid sequence was not found in the WT proteome by exact search | Priority score | -| NetMHCpan_MHCI_rank_bestRank | minimal MHC I binding rank score over all neoepitope candidates (8-11mers) and MHC I alleles | MHC I binding with netMHCpan | -| NetMHCpan_bestRank_peptide | neoepitope candidate sequence with minimal MHC I binding rank score | MHC I binding with netMHCpan | -| NetMHCpan_bestRank_allele | the MHC I allele related to ` NetMHCpan_bestRank_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity_affinity | minimal MHC I binding affinity over all neoepitope candidates (8-11mers) and MHC I alleles | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity_peptide | neoepitope candidate sequence with minimal MHC I binding affinity | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity_allele | the MHC I allele related to ` NetMHCpan_bestAffinity_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestRank9mer_rank | minimal MHC I binding rank score over all neoepitope candidates (9mers only) and MHC I alleles | MHC I binding with netMHCpan | -| NetMHCpan_bestRank9mer_peptide | neoepitope candidate sequence (9mer) with minimal MHC I binding rank score | MHC I binding with netMHCpan | -| NetMHCpan_bestRank9mer_allele | the MHC I allele related to `NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_affinity | minimal MHC I binding affinity over all neoepitope candidates (9mers) and MHC I alleles | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_allele | the MHC I allele related to ` NetMHCpan_bestAffinity9mer_peptide ` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_peptide | neoepitope candidate sequence (9mer) with minimal MHC I binding affinity | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity_affinityWT | MHC I binding affinity of `NetMHCpan_bestAffinity_peptideWT` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity_peptideWT | WT epitope that corresponds to ` NetMHCpan_bestAffinity_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestRank_rankWT | MHC I binding rank score of `NetMHCpan_bestRank_peptideWT` | MHC I binding with netMHCpan | -| NetMHCpan_bestRank_peptideWT | WT epitope that corresponds to `NetMHCpan_bestRank_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestRank9mer_rankWT | MHC I binding rank score of `NetMHCpan_bestRank9mer_peptideWT ` | MHC I binding with netMHCpan | -| NetMHCpan_bestRank9mer_peptideWT | WT epitope that corresponds to `NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_affinityWT | MHC I binding affinity of ` NetMHCpan_bestAffinity9mer_peptideWT ` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_rankWT | MHC I binding rank score of `NetMHCpan_bestAffinity9mer_peptideWT` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_peptideWT | WT epitope that corresponds to `NetMHCpan_bestAffinity9mer_peptide` | | -| PHBR_I | harmonic mean of minimal MHC I binding rank scores of all MHC I alleles of a patient | PHBR-I | -| NetMHCpan_bestAffinity9mer_positionMutation | indicates position of the mutation in ` NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_anchorMutated | mutation in ` NetMHCpan_bestRank9mer_peptide` in an anchor position (i.e. position 2 or 9) | anchor/non-anchor | -| NetMHCIIpan_bestRank_rank | minimal MHC II binding rank score over all neoepitope candidates (15mers) and all MHC II alleles | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestRank_peptide | neoepitope candidate sequence with minimal MHC II binding rank score | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestRank_allele | the MHC II isoform related to `NetMHCIIpan_bestRank_peptide` | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestAffinity_affinity | minimal MHC II binding affinity over all neoepitope candidates (15mers) and all MHC II alleles | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestAffinity_peptide | neoepitope candidate sequence with minimal MHC II binding affinity | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestAffinity_allele | the MHC II isoform related to ` NetMHCIIpan_bestAffinity_peptide` | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestRank_rankWT | minimal MHC II binding rank of `NetMHCIIpan_bestRank_peptideWT` | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestRank_peptideWT | WT epitope sequence (15mer) that corresponds to ` NetMHCIIpan_bestRank_peptide` | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestAffinity_affinityWT | minimal MHC II binding rank of `NetMHCIIpan_bestAffinity_peptideWT` | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestAffinity_peptideWT | WT epitope sequence (15mer) that corresponds to `NetMHCIIpan_bestAffinity_peptide` | MHC II binding with netMHCIIpan | -| PHBR_II | harmonic mean of minimal MHC II binding rank scores of all MHC II alleles of a patient | PHBR-II | -| Amplitude_MHCI_bestAffinity9mer | ratio of `NetMHCpan_bestAffinity9mer_affinity` and `NetMHCpan_bestAffinity9mer_affinityWT` | Recognition Potential | -| Amplitude_MHCI_bestAffinity | ratio of `NetMHCpan_bestAffinity_affinityWT` and `NetMHCpan_bestAffinity_affinity` | Generator rate | -| Amplitude_MHCII_bestRank | ratio of `NetMHCIIpan_bestRank_rank` and `NetMHCIIpan_bestRank_rankWT` | Generator rate | -| Pathogensimiliarity_MHCI_bestAffinity9mer | score representing the similarity of `NetMHCpan_bestAffinity9mer_peptide` to pathogen sequences in IEDB database | Recognition Potential | -| Pathogensimiliarity_MHCII_bestAffinity | score representing the similarity of `NetMHCIIpan_bestRank_peptide` to pathogen sequences in IEDB database | Recognition Potential | -| RecognitionPotential_MHCI_bestAffinity9mer | product of `Amplitude_MHCI_affinity_9mer` and `Pathogensimiliarity_MHCI_affinity_9mer` | Recognition Potential | -| DAI_MHCI_bestAffinity | difference of `NetMHCpan_bestAffinity_affinityWT` and `NetMHCpan_bestAffinity_affinity` | DAI | -| Classically_defined_neopeptide_MHCI | `NetMHCpan_bestAffinity_peptide`< 50 nM | Generator rate | -| Alternatively_defined_neopeptide_MHCI | `NetMHCpan_bestAffinity_peptide` < 5000 nM and `Amplitude_MHCI_bestAffinity` > 10 | Generator rate | -| Classically_defined_neopeptide_MHCII | `NetMHCIIpan_bestRank_rank` < 1 | Generator rate | -| Alternatively_defined_neopeptide_MHCII | `Best_rank_MHCII_score` < 4 and `Amplitude_MHCII_bestRank` < 2 | Generator rate | -| GeneratorRate_CDN_MHCI | number of neoepitope candidates with MHC I binding affinity < 50 nM per neoantigen canidate | Generator rate | -| GeneratorRate_ADN_MHCI | number of neoepitope candidates with MHC I binding affinity < 5000 nM per neoantigen canidate 10x better affinity in comparison to corresponding WT peptide | Generator rate | -| GeneratorRate_MHCI | sum of `GeneratorRate_CDN_MHCI` and `GeneratorRate_ADN_MHCI` | Generator rate | -| GeneratorRate_CDN_MHCII | number of neoepitope candidates with MHC II binding rank score < 1 per neoantigen canidate | Generator rate | -| GeneratorRate_ADN_MHCII | number of neoepitope candidates with MHC II binding rank score < 4 per neoantigen candidate 4x better rank in comparison to corresponding WT peptide | Generator rate | -| GeneratorRate_MHCII | sum of `GeneratorRate_CDN_MHCII` and `GeneratorRate_ADN_MHCII` | Generator rate | -| Tcell_predictor | output score of T cell predictor model | Tcell predictor | -| ImprovedBinder_MHCI | ratio of `NetMHCpan_MHCI_rank_bestRankWT` and `NetMHCpan_MHCI_rank_bestRank` > 1.2 | self-similarity | -| Selfsimilarity_MHCI_conserved_binder | score representing the similarity between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptideWT` For conservered binder only | self-similarity | -| Selfsimilarity_MHCI | score representing the similarity between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptide` | self-similarity | -| Selfsimilarity_MHCII | score representing the similarity between `NetMHCIIpan_bestAffinity_peptide` and `NetMHCIIpan_bestAffinity_peptide` | self-similarity | -| Number_of_mismatches_MCHI | number of amino acids that do no match between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptideWT` | Priority score | -| Priority_score | combinatorial score of several features such as MHC binding, expression and VAF | Priority score | -| Neoag_immunogenicity | output score of neoag model | neoag | -| IEDB_Immunogenicity_MHCI | IEDB Immunogenicity score for ` NetMHCpan_bestAffinity_peptide` | IEDB Immunogenicity | -| IEDB_Immunogenicity_MHCII | IEDB Immunogenicity score for `NetMHCIIpan_bestAffinity_peptide` | IEDB Immunogenicity | -| MixMHCpred_bestScore_peptide | MHC class I neoepitope candidate sequence with maximum MixMHCpred score over all neoepitope canidates (8-11mers) and MHC I alleles | MixMHCpred | -| MixMHCpred_bestScore_score | maximum MixMHCpred score over all neoepitope canidates (8-11mers) and MHC I alleles | MixMHCpred | -| MixMHCpred_bestScore_rank | rank that corresponds to `MixMHCpred_bestScore_score` | MixMHCpred | -| MixMHCpred_bestScore_allele | the allele with maximum MixMHCpred score | MixMHCpred | -| MixMHC2pred_bestRank_peptide | MHC class II neoepitope candidate sequence with minimal MixMHC2pred score over all neoepitope canidates (13-18mers) and MHC II alleles | MixMHC2pred | -| MixMHC2pred_bestRank_rank | minimal MixMHC2pred score over all neoepitope canidates (13-18mers) and MHC II alleles | MixMHC2pred | -| MixMHC2pred_bestRank_allele | the MHC II isoform with minimum MixMHC2pred rank score | MixMHC2pred | -| Dissimilarity_MHCI | score reflecting the dissimilarity of `NetMHCpan_bestAffinity_peptide` to the self-proteome | dissimilarity | -| Dissimilarity_MHCII | score reflecting the dissimilarity of `NetMHCIIpan_bestAffinity_peptide` to the self-proteome | dissimilarity | -| Vaxrank_bindingScore | total binding score of vaxrank | vaxrank | -| Vaxrank_totalScore | product of total binding score and expression score. Originally, the root of the number of reads supporting the mutation are used in the original implementation. To simplify, the expression normalised to VAF is used. | vaxrank | -| PRIME_bestScore_allele | best predicted MHC allele by PRIME model | PRIME | -| PRIME_bestScore_peptide | best predicted neoepitope candidate by PRIME model | PRIME | -| PRIME_bestScore_rank | output rank score of PRIME model | PRIME | -| PRIME_bestScore_score | output score of PRIME model | PRIME | -| HexAlignmentScore_MHCI | the alignment score by HEX for `NetMHCpan_bestAffinity_peptide` | HEX | -| HexAlignmentScore_MHCII | the alignment score by HEX for ` NetMHCIIpan_bestAffinity_peptide` | HEX | +| Column name | Description | Feature group/ Paper | +|---------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------| +| dnaVariantAlleleFrequency | the variant allele frequency calculated from the DNA | - | +| mutatedXmer | the long mutated amino acid sequence | - | +| wildTypeXmer | the long non-mutated amino acid sequence. This field shal be empty for alternative neoantigen classes | - | +| patientIdentifier | the patient identifier | - | +| rnaExpression | the RNA expression. If expression was imputed, this will will be `imputedGeneExpression` | expression | +| imputedGeneExpression | median gene expression in the TCGA cohort of the tumor entity provided in the patient file. | expression | +| rnaVariantAlleleFrequency | the variant allele frequency calculated from the RNA | - | +| gene | the HGNC gene symbol | - | +| Expression_mutated_transcript | transcript expression normalized by the variant allele frequency of the mutation | expression | +| mutation_not_found_in_proteome | indicates if mutated amino acid sequence was not found in the WT proteome by exact search | Priority score | +| NetMHCpan_bestRank_rank | minimal MHC I binding rank score over all neoepitope candidates (8-11mers) and MHC I alleles | MHC I binding with netMHCpan | +| NetMHCpan_bestRank_peptide | neoepitope candidate sequence with minimal MHC I binding rank score | MHC I binding with netMHCpan | +| NetMHCpan_bestRank_allele | the MHC I allele related to ` NetMHCpan_bestRank_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_affinity | minimal MHC I binding affinity over all neoepitope candidates (8-11mers) and MHC I alleles | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_peptide | neoepitope candidate sequence with minimal MHC I binding affinity | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_allele | the MHC I allele related to ` NetMHCpan_bestAffinity_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestRank9mer_rank | minimal MHC I binding rank score over all neoepitope candidates (9mers only) and MHC I alleles | MHC I binding with netMHCpan | +| NetMHCpan_bestRank9mer_peptide | neoepitope candidate sequence (9mer) with minimal MHC I binding rank score | MHC I binding with netMHCpan | +| NetMHCpan_bestRank9mer_allele | the MHC I allele related to `NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_affinity | minimal MHC I binding affinity over all neoepitope candidates (9mers) and MHC I alleles | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_allele | the MHC I allele related to ` NetMHCpan_bestAffinity9mer_peptide ` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_peptide | neoepitope candidate sequence (9mer) with minimal MHC I binding affinity | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_affinityWT | MHC I binding affinity of `NetMHCpan_bestAffinity_peptideWT` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_peptideWT | WT epitope that corresponds to ` NetMHCpan_bestAffinity_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestRank_rankWT | MHC I binding rank score of `NetMHCpan_bestRank_peptideWT` | MHC I binding with netMHCpan | +| NetMHCpan_bestRank_peptideWT | WT epitope that corresponds to `NetMHCpan_bestRank_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestRank9mer_rankWT | MHC I binding rank score of `NetMHCpan_bestRank9mer_peptideWT ` | MHC I binding with netMHCpan | +| NetMHCpan_bestRank9mer_peptideWT | WT epitope that corresponds to `NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_affinityWT | MHC I binding affinity of ` NetMHCpan_bestAffinity9mer_peptideWT ` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_peptideWT | WT epitope that corresponds to `NetMHCpan_bestAffinity9mer_peptide` | | +| PHBR_I | harmonic mean of minimal MHC I binding rank scores of all MHC I alleles of a patient | PHBR-I | +| NetMHCpan_bestAffinity9mer_positionMutation | indicates position of the mutation in ` NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_anchorMutated | mutation in ` NetMHCpan_bestRank9mer_peptide` in an anchor position (i.e. position 2 or 9) | anchor/non-anchor | +| NetMHCIIpan_bestRank_rank | minimal MHC II binding rank score over all neoepitope candidates (15mers) and all MHC II alleles | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestRank_peptide | neoepitope candidate sequence with minimal MHC II binding rank score | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestRank_allele | the MHC II isoform related to `NetMHCIIpan_bestRank_peptide` | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestAffinity_affinity | minimal MHC II binding affinity over all neoepitope candidates (15mers) and all MHC II alleles | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestAffinity_peptide | neoepitope candidate sequence with minimal MHC II binding affinity | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestAffinity_allele | the MHC II isoform related to ` NetMHCIIpan_bestAffinity_peptide` | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestRank_rankWT | minimal MHC II binding rank of `NetMHCIIpan_bestRank_peptideWT` | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestRank_peptideWT | WT epitope sequence (15mer) that corresponds to ` NetMHCIIpan_bestRank_peptide` | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestAffinity_affinityWT | minimal MHC II binding rank of `NetMHCIIpan_bestAffinity_peptideWT` | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestAffinity_peptideWT | WT epitope sequence (15mer) that corresponds to `NetMHCIIpan_bestAffinity_peptide` | MHC II binding with netMHCIIpan | +| PHBR_II | harmonic mean of minimal MHC II binding rank scores of all MHC II alleles of a patient | PHBR-II | +| Amplitude_MHCI_bestAffinity9mer | ratio of `NetMHCpan_bestAffinity9mer_affinity` and `NetMHCpan_bestAffinity9mer_affinityWT` | Recognition Potential | +| Amplitude_MHCI_bestAffinity | ratio of `NetMHCpan_bestAffinity_affinityWT` and `NetMHCpan_bestAffinity_affinity` | Generator rate | +| Amplitude_MHCII_bestRank | ratio of `NetMHCIIpan_bestRank_rank` and `NetMHCIIpan_bestRank_rankWT` | Generator rate | +| Pathogensimiliarity_MHCI_bestAffinity9mer | score representing the similarity of `NetMHCpan_bestAffinity9mer_peptide` to pathogen sequences in IEDB database | Recognition Potential | +| Pathogensimiliarity_MHCII_bestAffinity | score representing the similarity of `NetMHCIIpan_bestRank_peptide` to pathogen sequences in IEDB database | Recognition Potential | +| RecognitionPotential_MHCI_bestAffinity9mer | product of `Amplitude_MHCI_affinity_9mer` and `Pathogensimiliarity_MHCI_affinity_9mer` | Recognition Potential | +| DAI_MHCI_bestAffinity | difference of `NetMHCpan_bestAffinity_affinityWT` and `NetMHCpan_bestAffinity_affinity` | DAI | +| Classically_defined_neopeptide_MHCI | `NetMHCpan_bestAffinity_peptide`< 50 nM | Generator rate | +| Alternatively_defined_neopeptide_MHCI | `NetMHCpan_bestAffinity_peptide` < 5000 nM and `Amplitude_MHCI_bestAffinity` > 10 | Generator rate | +| Classically_defined_neopeptide_MHCII | `NetMHCIIpan_bestRank_rank` < 1 | Generator rate | +| Alternatively_defined_neopeptide_MHCII | `Best_rank_MHCII_score` < 4 and `Amplitude_MHCII_bestRank` < 2 | Generator rate | +| GeneratorRate_CDN_MHCI | number of neoepitope candidates with MHC I binding affinity < 50 nM per neoantigen canidate | Generator rate | +| GeneratorRate_ADN_MHCI | number of neoepitope candidates with MHC I binding affinity < 5000 nM per neoantigen canidate 10x better affinity in comparison to corresponding WT peptide | Generator rate | +| GeneratorRate_MHCI | sum of `GeneratorRate_CDN_MHCI` and `GeneratorRate_ADN_MHCI` | Generator rate | +| GeneratorRate_CDN_MHCII | number of neoepitope candidates with MHC II binding rank score < 1 per neoantigen canidate | Generator rate | +| GeneratorRate_ADN_MHCII | number of neoepitope candidates with MHC II binding rank score < 4 per neoantigen candidate 4x better rank in comparison to corresponding WT peptide | Generator rate | +| GeneratorRate_MHCII | sum of `GeneratorRate_CDN_MHCII` and `GeneratorRate_ADN_MHCII` | Generator rate | +| Tcell_predictor | output score of T cell predictor model | Tcell predictor | +| ImprovedBinder_MHCI | ratio of `NetMHCpan_MHCI_rank_bestRankWT` and `NetMHCpan_MHCI_rank_bestRank` > 1.2 | self-similarity | +| Selfsimilarity_MHCI_conserved_binder | score representing the similarity between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptideWT` For conservered binder only | self-similarity | +| Selfsimilarity_MHCI | score representing the similarity between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptide` | self-similarity | +| Selfsimilarity_MHCII | score representing the similarity between `NetMHCIIpan_bestAffinity_peptide` and `NetMHCIIpan_bestAffinity_peptide` | self-similarity | +| Number_of_mismatches_MCHI | number of amino acids that do no match between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptideWT` | Priority score | +| Priority_score | combinatorial score of several features such as MHC binding, expression and VAF | Priority score | +| Neoag_immunogenicity | output score of neoag model | neoag | +| IEDB_Immunogenicity_MHCI | IEDB Immunogenicity score for ` NetMHCpan_bestAffinity_peptide` | IEDB Immunogenicity | +| IEDB_Immunogenicity_MHCII | IEDB Immunogenicity score for `NetMHCIIpan_bestAffinity_peptide` | IEDB Immunogenicity | +| MixMHCpred_bestScore_peptide | MHC class I neoepitope candidate sequence with maximum MixMHCpred score over all neoepitope canidates (8-11mers) and MHC I alleles | MixMHCpred | +| MixMHCpred_bestScore_score | maximum MixMHCpred score over all neoepitope canidates (8-11mers) and MHC I alleles | MixMHCpred | +| MixMHCpred_bestScore_rank | rank that corresponds to `MixMHCpred_bestScore_score` | MixMHCpred | +| MixMHCpred_bestScore_allele | the allele with maximum MixMHCpred score | MixMHCpred | +| MixMHC2pred_bestRank_peptide | MHC class II neoepitope candidate sequence with minimal MixMHC2pred score over all neoepitope canidates (13-18mers) and MHC II alleles | MixMHC2pred | +| MixMHC2pred_bestRank_rank | minimal MixMHC2pred score over all neoepitope canidates (13-18mers) and MHC II alleles | MixMHC2pred | +| MixMHC2pred_bestRank_allele | the MHC II isoform with minimum MixMHC2pred rank score | MixMHC2pred | +| Dissimilarity_MHCI | score reflecting the dissimilarity of `NetMHCpan_bestAffinity_peptide` to the self-proteome | dissimilarity | +| Dissimilarity_MHCII | score reflecting the dissimilarity of `NetMHCIIpan_bestAffinity_peptide` to the self-proteome | dissimilarity | +| Vaxrank_bindingScore | total binding score of vaxrank | vaxrank | +| Vaxrank_totalScore | product of total binding score and expression score. Originally, the root of the number of reads supporting the mutation are used in the original implementation. To simplify, the expression normalised to VAF is used. | vaxrank | +| PRIME_bestScore_allele | best predicted MHC allele by PRIME model | PRIME | +| PRIME_bestScore_peptide | best predicted neoepitope candidate by PRIME model | PRIME | +| PRIME_bestScore_rank | output rank score of PRIME model | PRIME | +| PRIME_bestScore_score | output score of PRIME model | PRIME | +| HexAlignmentScore_MHCI | the alignment score by HEX for `NetMHCpan_bestAffinity_peptide` | HEX | +| HexAlignmentScore_MHCII | the alignment score by HEX for ` NetMHCIIpan_bestAffinity_peptide` | HEX | In addition, all logging output is appended to a log file with the suffix diff --git a/neofox/__init__.py b/neofox/__init__.py index ebb9e254..f01e974f 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b6" +VERSION = "1.1.0b7" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" From 7b9b9472dd9f102aff2214384acc3742d802e50b Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Wed, 1 Mar 2023 11:15:48 +0100 Subject: [PATCH 08/83] edit spaces automation --- docs/source/03_02_output_data.md | 180 +++++++++++++++---------------- 1 file changed, 90 insertions(+), 90 deletions(-) diff --git a/docs/source/03_02_output_data.md b/docs/source/03_02_output_data.md index 29447506..7e1abbff 100755 --- a/docs/source/03_02_output_data.md +++ b/docs/source/03_02_output_data.md @@ -12,96 +12,96 @@ The following table describes each of the annotations in the output: **TABLE 1** -| Column name | Description | Feature group/ Paper | -|---------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------| -| dnaVariantAlleleFrequency | the variant allele frequency calculated from the DNA | - | -| mutatedXmer | the long mutated amino acid sequence | - | -| wildTypeXmer | the long non-mutated amino acid sequence. This field shal be empty for alternative neoantigen classes | - | -| patientIdentifier | the patient identifier | - | -| rnaExpression | the RNA expression. If expression was imputed, this will will be `imputedGeneExpression` | expression | -| imputedGeneExpression | median gene expression in the TCGA cohort of the tumor entity provided in the patient file. | expression | -| rnaVariantAlleleFrequency | the variant allele frequency calculated from the RNA | - | -| gene | the HGNC gene symbol | - | -| Expression_mutated_transcript | transcript expression normalized by the variant allele frequency of the mutation | expression | -| mutation_not_found_in_proteome | indicates if mutated amino acid sequence was not found in the WT proteome by exact search | Priority score | -| NetMHCpan_bestRank_rank | minimal MHC I binding rank score over all neoepitope candidates (8-11mers) and MHC I alleles | MHC I binding with netMHCpan | -| NetMHCpan_bestRank_peptide | neoepitope candidate sequence with minimal MHC I binding rank score | MHC I binding with netMHCpan | -| NetMHCpan_bestRank_allele | the MHC I allele related to ` NetMHCpan_bestRank_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity_affinity | minimal MHC I binding affinity over all neoepitope candidates (8-11mers) and MHC I alleles | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity_peptide | neoepitope candidate sequence with minimal MHC I binding affinity | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity_allele | the MHC I allele related to ` NetMHCpan_bestAffinity_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestRank9mer_rank | minimal MHC I binding rank score over all neoepitope candidates (9mers only) and MHC I alleles | MHC I binding with netMHCpan | -| NetMHCpan_bestRank9mer_peptide | neoepitope candidate sequence (9mer) with minimal MHC I binding rank score | MHC I binding with netMHCpan | -| NetMHCpan_bestRank9mer_allele | the MHC I allele related to `NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_affinity | minimal MHC I binding affinity over all neoepitope candidates (9mers) and MHC I alleles | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_allele | the MHC I allele related to ` NetMHCpan_bestAffinity9mer_peptide ` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_peptide | neoepitope candidate sequence (9mer) with minimal MHC I binding affinity | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity_affinityWT | MHC I binding affinity of `NetMHCpan_bestAffinity_peptideWT` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity_peptideWT | WT epitope that corresponds to ` NetMHCpan_bestAffinity_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestRank_rankWT | MHC I binding rank score of `NetMHCpan_bestRank_peptideWT` | MHC I binding with netMHCpan | -| NetMHCpan_bestRank_peptideWT | WT epitope that corresponds to `NetMHCpan_bestRank_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestRank9mer_rankWT | MHC I binding rank score of `NetMHCpan_bestRank9mer_peptideWT ` | MHC I binding with netMHCpan | -| NetMHCpan_bestRank9mer_peptideWT | WT epitope that corresponds to `NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_affinityWT | MHC I binding affinity of ` NetMHCpan_bestAffinity9mer_peptideWT ` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_peptideWT | WT epitope that corresponds to `NetMHCpan_bestAffinity9mer_peptide` | | -| PHBR_I | harmonic mean of minimal MHC I binding rank scores of all MHC I alleles of a patient | PHBR-I | -| NetMHCpan_bestAffinity9mer_positionMutation | indicates position of the mutation in ` NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_anchorMutated | mutation in ` NetMHCpan_bestRank9mer_peptide` in an anchor position (i.e. position 2 or 9) | anchor/non-anchor | -| NetMHCIIpan_bestRank_rank | minimal MHC II binding rank score over all neoepitope candidates (15mers) and all MHC II alleles | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestRank_peptide | neoepitope candidate sequence with minimal MHC II binding rank score | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestRank_allele | the MHC II isoform related to `NetMHCIIpan_bestRank_peptide` | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestAffinity_affinity | minimal MHC II binding affinity over all neoepitope candidates (15mers) and all MHC II alleles | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestAffinity_peptide | neoepitope candidate sequence with minimal MHC II binding affinity | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestAffinity_allele | the MHC II isoform related to ` NetMHCIIpan_bestAffinity_peptide` | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestRank_rankWT | minimal MHC II binding rank of `NetMHCIIpan_bestRank_peptideWT` | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestRank_peptideWT | WT epitope sequence (15mer) that corresponds to ` NetMHCIIpan_bestRank_peptide` | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestAffinity_affinityWT | minimal MHC II binding rank of `NetMHCIIpan_bestAffinity_peptideWT` | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestAffinity_peptideWT | WT epitope sequence (15mer) that corresponds to `NetMHCIIpan_bestAffinity_peptide` | MHC II binding with netMHCIIpan | -| PHBR_II | harmonic mean of minimal MHC II binding rank scores of all MHC II alleles of a patient | PHBR-II | -| Amplitude_MHCI_bestAffinity9mer | ratio of `NetMHCpan_bestAffinity9mer_affinity` and `NetMHCpan_bestAffinity9mer_affinityWT` | Recognition Potential | -| Amplitude_MHCI_bestAffinity | ratio of `NetMHCpan_bestAffinity_affinityWT` and `NetMHCpan_bestAffinity_affinity` | Generator rate | -| Amplitude_MHCII_bestRank | ratio of `NetMHCIIpan_bestRank_rank` and `NetMHCIIpan_bestRank_rankWT` | Generator rate | -| Pathogensimiliarity_MHCI_bestAffinity9mer | score representing the similarity of `NetMHCpan_bestAffinity9mer_peptide` to pathogen sequences in IEDB database | Recognition Potential | -| Pathogensimiliarity_MHCII_bestAffinity | score representing the similarity of `NetMHCIIpan_bestRank_peptide` to pathogen sequences in IEDB database | Recognition Potential | -| RecognitionPotential_MHCI_bestAffinity9mer | product of `Amplitude_MHCI_affinity_9mer` and `Pathogensimiliarity_MHCI_affinity_9mer` | Recognition Potential | -| DAI_MHCI_bestAffinity | difference of `NetMHCpan_bestAffinity_affinityWT` and `NetMHCpan_bestAffinity_affinity` | DAI | -| Classically_defined_neopeptide_MHCI | `NetMHCpan_bestAffinity_peptide`< 50 nM | Generator rate | -| Alternatively_defined_neopeptide_MHCI | `NetMHCpan_bestAffinity_peptide` < 5000 nM and `Amplitude_MHCI_bestAffinity` > 10 | Generator rate | -| Classically_defined_neopeptide_MHCII | `NetMHCIIpan_bestRank_rank` < 1 | Generator rate | -| Alternatively_defined_neopeptide_MHCII | `Best_rank_MHCII_score` < 4 and `Amplitude_MHCII_bestRank` < 2 | Generator rate | -| GeneratorRate_CDN_MHCI | number of neoepitope candidates with MHC I binding affinity < 50 nM per neoantigen canidate | Generator rate | -| GeneratorRate_ADN_MHCI | number of neoepitope candidates with MHC I binding affinity < 5000 nM per neoantigen canidate 10x better affinity in comparison to corresponding WT peptide | Generator rate | -| GeneratorRate_MHCI | sum of `GeneratorRate_CDN_MHCI` and `GeneratorRate_ADN_MHCI` | Generator rate | -| GeneratorRate_CDN_MHCII | number of neoepitope candidates with MHC II binding rank score < 1 per neoantigen canidate | Generator rate | -| GeneratorRate_ADN_MHCII | number of neoepitope candidates with MHC II binding rank score < 4 per neoantigen candidate 4x better rank in comparison to corresponding WT peptide | Generator rate | -| GeneratorRate_MHCII | sum of `GeneratorRate_CDN_MHCII` and `GeneratorRate_ADN_MHCII` | Generator rate | -| Tcell_predictor | output score of T cell predictor model | Tcell predictor | -| ImprovedBinder_MHCI | ratio of `NetMHCpan_MHCI_rank_bestRankWT` and `NetMHCpan_MHCI_rank_bestRank` > 1.2 | self-similarity | -| Selfsimilarity_MHCI_conserved_binder | score representing the similarity between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptideWT` For conservered binder only | self-similarity | -| Selfsimilarity_MHCI | score representing the similarity between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptide` | self-similarity | -| Selfsimilarity_MHCII | score representing the similarity between `NetMHCIIpan_bestAffinity_peptide` and `NetMHCIIpan_bestAffinity_peptide` | self-similarity | -| Number_of_mismatches_MCHI | number of amino acids that do no match between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptideWT` | Priority score | -| Priority_score | combinatorial score of several features such as MHC binding, expression and VAF | Priority score | -| Neoag_immunogenicity | output score of neoag model | neoag | -| IEDB_Immunogenicity_MHCI | IEDB Immunogenicity score for ` NetMHCpan_bestAffinity_peptide` | IEDB Immunogenicity | -| IEDB_Immunogenicity_MHCII | IEDB Immunogenicity score for `NetMHCIIpan_bestAffinity_peptide` | IEDB Immunogenicity | -| MixMHCpred_bestScore_peptide | MHC class I neoepitope candidate sequence with maximum MixMHCpred score over all neoepitope canidates (8-11mers) and MHC I alleles | MixMHCpred | -| MixMHCpred_bestScore_score | maximum MixMHCpred score over all neoepitope canidates (8-11mers) and MHC I alleles | MixMHCpred | -| MixMHCpred_bestScore_rank | rank that corresponds to `MixMHCpred_bestScore_score` | MixMHCpred | -| MixMHCpred_bestScore_allele | the allele with maximum MixMHCpred score | MixMHCpred | -| MixMHC2pred_bestRank_peptide | MHC class II neoepitope candidate sequence with minimal MixMHC2pred score over all neoepitope canidates (13-18mers) and MHC II alleles | MixMHC2pred | -| MixMHC2pred_bestRank_rank | minimal MixMHC2pred score over all neoepitope canidates (13-18mers) and MHC II alleles | MixMHC2pred | -| MixMHC2pred_bestRank_allele | the MHC II isoform with minimum MixMHC2pred rank score | MixMHC2pred | -| Dissimilarity_MHCI | score reflecting the dissimilarity of `NetMHCpan_bestAffinity_peptide` to the self-proteome | dissimilarity | -| Dissimilarity_MHCII | score reflecting the dissimilarity of `NetMHCIIpan_bestAffinity_peptide` to the self-proteome | dissimilarity | -| Vaxrank_bindingScore | total binding score of vaxrank | vaxrank | -| Vaxrank_totalScore | product of total binding score and expression score. Originally, the root of the number of reads supporting the mutation are used in the original implementation. To simplify, the expression normalised to VAF is used. | vaxrank | -| PRIME_bestScore_allele | best predicted MHC allele by PRIME model | PRIME | -| PRIME_bestScore_peptide | best predicted neoepitope candidate by PRIME model | PRIME | -| PRIME_bestScore_rank | output rank score of PRIME model | PRIME | -| PRIME_bestScore_score | output score of PRIME model | PRIME | -| HexAlignmentScore_MHCI | the alignment score by HEX for `NetMHCpan_bestAffinity_peptide` | HEX | -| HexAlignmentScore_MHCII | the alignment score by HEX for ` NetMHCIIpan_bestAffinity_peptide` | HEX | +| Column name | Description | Feature group/ Paper | +|---------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------| +| dnaVariantAlleleFrequency | the variant allele frequency calculated from the DNA | - | +| mutatedXmer | the long mutated amino acid sequence | - | +| wildTypeXmer | the long non-mutated amino acid sequence. This field shall be empty for alternative neoantigen classes | - | +| patientIdentifier | the patient identifier | - | +| rnaExpression | the RNA expression. If expression was imputed, this will will be `imputedGeneExpression` | expression | +| imputedGeneExpression | median gene expression in the TCGA cohort of the tumor entity provided in the patient file. | expression | +| rnaVariantAlleleFrequency | the variant allele frequency calculated from the RNA | - | +| gene | the HGNC gene symbol | - | +| Expression_mutated_transcript | transcript expression normalized by the variant allele frequency of the mutation | expression | +| mutation_not_found_in_proteome | indicates if mutated amino acid sequence was not found in the WT proteome by exact search | Priority score | +| NetMHCpan_bestRank_rank | minimal MHC I binding rank score over all neoepitope candidates (8-11mers) and MHC I alleles | MHC I binding with netMHCpan | +| NetMHCpan_bestRank_peptide | neoepitope candidate sequence with minimal MHC I binding rank score | MHC I binding with netMHCpan | +| NetMHCpan_bestRank_allele | the MHC I allele related to `NetMHCpan_bestRank_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_affinity | minimal MHC I binding affinity over all neoepitope candidates (8-11mers) and MHC I alleles | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_peptide | neoepitope candidate sequence with minimal MHC I binding affinity | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_allele | the MHC I allele related to `NetMHCpan_bestAffinity_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestRank9mer_rank | minimal MHC I binding rank score over all neoepitope candidates (9mers only) and MHC I alleles | MHC I binding with netMHCpan | +| NetMHCpan_bestRank9mer_peptide | neoepitope candidate sequence (9mer) with minimal MHC I binding rank score | MHC I binding with netMHCpan | +| NetMHCpan_bestRank9mer_allele | the MHC I allele related to `NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_affinity | minimal MHC I binding affinity over all neoepitope candidates (9mers) and MHC I alleles | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_allele | the MHC I allele related to `NetMHCpan_bestAffinity9mer_peptide ` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_peptide | neoepitope candidate sequence (9mer) with minimal MHC I binding affinity | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_affinityWT | MHC I binding affinity of `NetMHCpan_bestAffinity_peptideWT` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_peptideWT | WT epitope that corresponds to `NetMHCpan_bestAffinity_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestRank_rankWT | MHC I binding rank score of `NetMHCpan_bestRank_peptideWT` | MHC I binding with netMHCpan | +| NetMHCpan_bestRank_peptideWT | WT epitope that corresponds to `NetMHCpan_bestRank_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestRank9mer_rankWT | MHC I binding rank score of `NetMHCpan_bestRank9mer_peptideWT ` | MHC I binding with netMHCpan | +| NetMHCpan_bestRank9mer_peptideWT | WT epitope that corresponds to `NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_affinityWT | MHC I binding affinity of ` NetMHCpan_bestAffinity9mer_peptideWT ` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_peptideWT | WT epitope that corresponds to `NetMHCpan_bestAffinity9mer_peptide` | | +| PHBR_I | harmonic mean of minimal MHC I binding rank scores of all MHC I alleles of a patient | PHBR-I | +| NetMHCpan_bestAffinity9mer_positionMutation | indicates position of the mutation in ` NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_anchorMutated | mutation in `NetMHCpan_bestRank9mer_peptide` in an anchor position (i.e. position 2 or 9) | anchor/non-anchor | +| NetMHCIIpan_bestRank_rank | minimal MHC II binding rank score over all neoepitope candidates (15mers) and all MHC II alleles | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestRank_peptide | neoepitope candidate sequence with minimal MHC II binding rank score | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestRank_allele | the MHC II isoform related to `NetMHCIIpan_bestRank_peptide` | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestAffinity_affinity | minimal MHC II binding affinity over all neoepitope candidates (15mers) and all MHC II alleles | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestAffinity_peptide | neoepitope candidate sequence with minimal MHC II binding affinity | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestAffinity_allele | the MHC II isoform related to `NetMHCIIpan_bestAffinity_peptide` | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestRank_rankWT | minimal MHC II binding rank of `NetMHCIIpan_bestRank_peptideWT` | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestRank_peptideWT | WT epitope sequence (15mer) that corresponds to ` NetMHCIIpan_bestRank_peptide` | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestAffinity_affinityWT | minimal MHC II binding rank of `NetMHCIIpan_bestAffinity_peptideWT` | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestAffinity_peptideWT | WT epitope sequence (15mer) that corresponds to `NetMHCIIpan_bestAffinity_peptide` | MHC II binding with netMHCIIpan | +| PHBR_II | harmonic mean of minimal MHC II binding rank scores of all MHC II alleles of a patient | PHBR-II | +| Amplitude_MHCI_bestAffinity9mer | ratio of `NetMHCpan_bestAffinity9mer_affinity` and `NetMHCpan_bestAffinity9mer_affinityWT` | Recognition Potential | +| Amplitude_MHCI_bestAffinity | ratio of `NetMHCpan_bestAffinity_affinityWT` and `NetMHCpan_bestAffinity_affinity` | Generator rate | +| Amplitude_MHCII_bestRank | ratio of `NetMHCIIpan_bestRank_rank` and `NetMHCIIpan_bestRank_rankWT` | Generator rate | +| Pathogensimiliarity_MHCI_bestAffinity9mer | score representing the similarity of `NetMHCpan_bestAffinity9mer_peptide` to pathogen sequences in IEDB database | Recognition Potential | +| Pathogensimiliarity_MHCII_bestAffinity | score representing the similarity of `NetMHCIIpan_bestRank_peptide` to pathogen sequences in IEDB database | Recognition Potential | +| RecognitionPotential_MHCI_bestAffinity9mer | product of `Amplitude_MHCI_affinity_9mer` and `Pathogensimiliarity_MHCI_affinity_9mer` | Recognition Potential | +| DAI_MHCI_bestAffinity | difference of `NetMHCpan_bestAffinity_affinityWT` and `NetMHCpan_bestAffinity_affinity` | DAI | +| Classically_defined_neopeptide_MHCI | `NetMHCpan_bestAffinity_peptide`< 50 nM | Generator rate | +| Alternatively_defined_neopeptide_MHCI | `NetMHCpan_bestAffinity_peptide` < 5000 nM and `Amplitude_MHCI_bestAffinity` > 10 | Generator rate | +| Classically_defined_neopeptide_MHCII | `NetMHCIIpan_bestRank_rank` < 1 | Generator rate | +| Alternatively_defined_neopeptide_MHCII | `Best_rank_MHCII_score` < 4 and `Amplitude_MHCII_bestRank` < 2 | Generator rate | +| GeneratorRate_CDN_MHCI | number of neoepitope candidates with MHC I binding affinity < 50 nM per neoantigen canidate | Generator rate | +| GeneratorRate_ADN_MHCI | number of neoepitope candidates with MHC I binding affinity < 5000 nM per neoantigen canidate 10x better affinity in comparison to corresponding WT peptide | Generator rate | +| GeneratorRate_MHCI | sum of `GeneratorRate_CDN_MHCI` and `GeneratorRate_ADN_MHCI` | Generator rate | +| GeneratorRate_CDN_MHCII | number of neoepitope candidates with MHC II binding rank score < 1 per neoantigen canidate | Generator rate | +| GeneratorRate_ADN_MHCII | number of neoepitope candidates with MHC II binding rank score < 4 per neoantigen candidate 4x better rank in comparison to corresponding WT peptide | Generator rate | +| GeneratorRate_MHCII | sum of `GeneratorRate_CDN_MHCII` and `GeneratorRate_ADN_MHCII` | Generator rate | +| Tcell_predictor | output score of T cell predictor model | Tcell predictor | +| ImprovedBinder_MHCI | ratio of `NetMHCpan_MHCI_rank_bestRankWT` and `NetMHCpan_MHCI_rank_bestRank` > 1.2 | self-similarity | +| Selfsimilarity_MHCI_conserved_binder | score representing the similarity between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptideWT` For conservered binder only | self-similarity | +| Selfsimilarity_MHCI | score representing the similarity between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptide` | self-similarity | +| Selfsimilarity_MHCII | score representing the similarity between `NetMHCIIpan_bestAffinity_peptide` and `NetMHCIIpan_bestAffinity_peptide` | self-similarity | +| Number_of_mismatches_MCHI | number of amino acids that do no match between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptideWT` | Priority score | +| Priority_score | combinatorial score of several features such as MHC binding, expression and VAF | Priority score | +| Neoag_immunogenicity | output score of neoag model | neoag | +| IEDB_Immunogenicity_MHCI | IEDB Immunogenicity score for `NetMHCpan_bestAffinity_peptide` | IEDB Immunogenicity | +| IEDB_Immunogenicity_MHCII | IEDB Immunogenicity score for `NetMHCIIpan_bestAffinity_peptide` | IEDB Immunogenicity | +| MixMHCpred_bestScore_peptide | MHC class I neoepitope candidate sequence with maximum MixMHCpred score over all neoepitope canidates (8-11mers) and MHC I alleles | MixMHCpred | +| MixMHCpred_bestScore_score | maximum MixMHCpred score over all neoepitope canidates (8-11mers) and MHC I alleles | MixMHCpred | +| MixMHCpred_bestScore_rank | rank that corresponds to `MixMHCpred_bestScore_score` | MixMHCpred | +| MixMHCpred_bestScore_allele | the allele with maximum MixMHCpred score | MixMHCpred | +| MixMHC2pred_bestRank_peptide | MHC class II neoepitope candidate sequence with minimal MixMHC2pred score over all neoepitope canidates (13-18mers) and MHC II alleles | MixMHC2pred | +| MixMHC2pred_bestRank_rank | minimal MixMHC2pred score over all neoepitope canidates (13-18mers) and MHC II alleles | MixMHC2pred | +| MixMHC2pred_bestRank_allele | the MHC II isoform with minimum MixMHC2pred rank score | MixMHC2pred | +| Dissimilarity_MHCI | score reflecting the dissimilarity of `NetMHCpan_bestAffinity_peptide` to the self-proteome | dissimilarity | +| Dissimilarity_MHCII | score reflecting the dissimilarity of `NetMHCIIpan_bestAffinity_peptide` to the self-proteome | dissimilarity | +| Vaxrank_bindingScore | total binding score of vaxrank | vaxrank | +| Vaxrank_totalScore | product of total binding score and expression score. Originally, the root of the number of reads supporting the mutation are used in the original implementation. To simplify, the expression normalised to VAF is used. | vaxrank | +| PRIME_bestScore_allele | best predicted MHC allele by PRIME model | PRIME | +| PRIME_bestScore_peptide | best predicted neoepitope candidate by PRIME model | PRIME | +| PRIME_bestScore_rank | output rank score of PRIME model | PRIME | +| PRIME_bestScore_score | output score of PRIME model | PRIME | +| HexAlignmentScore_MHCI | the alignment score by HEX for `NetMHCpan_bestAffinity_peptide` | HEX | +| HexAlignmentScore_MHCII | the alignment score by HEX for `NetMHCIIpan_bestAffinity_peptide` | HEX | In addition, all logging output is appended to a log file with the suffix From 5d2985fef9f720dee7eb0216cc7b7f1967ea067b Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Wed, 1 Mar 2023 11:27:29 +0100 Subject: [PATCH 09/83] edit spaces automation --- neofox/__init__.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index f01e974f..1c226185 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b7" +VERSION = "1.1.0b9" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" From 0278ea9ab0d6793745c5350cbfe4a8c991ebfda9 Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Wed, 8 Mar 2023 15:03:29 +0100 Subject: [PATCH 10/83] file changes in my folder --- .github/workflows/release.yml | 0 .readthedocs.yml | 0 Dockerfile | 0 LICENSE | 0 docs/source/03_02_output_data.md | 181 +++++----- docs/source/03_03_usage.md | 2 +- docs/source/05_models.md | 1 - gpl-v3.tmpl | 0 ...combine_netmhcpan_pred_multiple_binders.py | 2 +- neofox/__init__.py | 3 +- neofox/annotator/abstract_annotator.py | 2 +- neofox/command_line.py | 24 +- neofox/model/conversion.py | 1 - neofox/model/factories.py | 3 +- neofox/model/mhc_parser.py | 2 +- neofox/model/models.md | 1 - neofox/model/neoantigen.proto | 10 +- neofox/model/neoantigen.py | 8 +- neofox/neofox.py | 6 +- neofox/neofox_epitope.py | 2 - neofox/published_features/hex/BLOSUM62.rda | Bin 532 -> 0 bytes .../published_features/hex/EPItOMe_modified.R | 309 ------------------ neofox/published_features/hex/hex.R | 41 --- neofox/published_features/hex/hex.py | 19 +- neofox/published_features/hex/pyhex.py | 51 +++ neofox/references/install_r_dependencies.R | 6 - neofox/tests/integration_tests/test_hex.py | 27 +- neofox/tests/integration_tests/test_neofox.py | 2 - neofox/tests/synthetic_data/factories.py | 1 - .../tests/unit_tests/test_model_converter.py | 6 - neofox/tests/unit_tests/test_neofox.py | 13 +- neofox/tests/unit_tests/test_validation.py | 22 +- 32 files changed, 189 insertions(+), 556 deletions(-) mode change 100644 => 100755 .github/workflows/release.yml mode change 100644 => 100755 .readthedocs.yml mode change 100644 => 100755 Dockerfile mode change 100644 => 100755 LICENSE mode change 100644 => 100755 gpl-v3.tmpl delete mode 100644 neofox/published_features/hex/BLOSUM62.rda delete mode 100644 neofox/published_features/hex/EPItOMe_modified.R delete mode 100644 neofox/published_features/hex/hex.R create mode 100644 neofox/published_features/hex/pyhex.py mode change 100644 => 100755 neofox/tests/synthetic_data/factories.py mode change 100644 => 100755 neofox/tests/unit_tests/test_validation.py diff --git a/.github/workflows/release.yml b/.github/workflows/release.yml old mode 100644 new mode 100755 diff --git a/.readthedocs.yml b/.readthedocs.yml old mode 100644 new mode 100755 diff --git a/Dockerfile b/Dockerfile old mode 100644 new mode 100755 diff --git a/LICENSE b/LICENSE old mode 100644 new mode 100755 diff --git a/docs/source/03_02_output_data.md b/docs/source/03_02_output_data.md index 6d612cc2..7e1abbff 100755 --- a/docs/source/03_02_output_data.md +++ b/docs/source/03_02_output_data.md @@ -12,97 +12,96 @@ The following table describes each of the annotations in the output: **TABLE 1** -| Column name | Description | Feature group/ Paper | -|----------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------| -| dnaVariantAlleleFrequency | the variant allele frequency calculated from the DNA | - | -| mutation.mutatedXmer | the long mutated amino acid sequence | - | -| mutation.wildTypeXmer | the long non-mutated amino acid sequence. This field shal be empty for alternative neoantigen classes | - | -| patientIdentifier | the patient identifier | - | -| rnaExpression | the RNA expression. If expression was imputed, this will will be `imputedGeneExpression` | expression | -| imputedGeneExpression | median gene expression in the TCGA cohort of the tumor entity provided in the patient file. | expression | -| rnaVariantAlleleFrequency | the variant allele frequency calculated from the RNA | - | -| gene | the HGNC gene symbol | - | -| Expression_mutated_transcript | transcript expression normalized by the variant allele frequency of the mutation | expression | -| mutation_not_found_in_proteome | indicates if mutated amino acid sequence was not found in the WT proteome by exact search | Priority score | -| NetMHCpan_MHCI_rank_bestRank | minimal MHC I binding rank score over all neoepitope candidates (8-11mers) and MHC I alleles | MHC I binding with netMHCpan | -| NetMHCpan_bestRank_peptide | neoepitope candidate sequence with minimal MHC I binding rank score | MHC I binding with netMHCpan | -| NetMHCpan_bestRank_allele | the MHC I allele related to ` NetMHCpan_bestRank_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity_affinity | minimal MHC I binding affinity over all neoepitope candidates (8-11mers) and MHC I alleles | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity_peptide | neoepitope candidate sequence with minimal MHC I binding affinity | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity_allele | the MHC I allele related to ` NetMHCpan_bestAffinity_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestRank9mer_rank | minimal MHC I binding rank score over all neoepitope candidates (9mers only) and MHC I alleles | MHC I binding with netMHCpan | -| NetMHCpan_bestRank9mer_peptide | neoepitope candidate sequence (9mer) with minimal MHC I binding rank score | MHC I binding with netMHCpan | -| NetMHCpan_bestRank9mer_allele | the MHC I allele related to `NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_affinity | minimal MHC I binding affinity over all neoepitope candidates (9mers) and MHC I alleles | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_allele | the MHC I allele related to ` NetMHCpan_bestAffinity9mer_peptide ` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_peptide | neoepitope candidate sequence (9mer) with minimal MHC I binding affinity | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity_affinityWT | MHC I binding affinity of `NetMHCpan_bestAffinity_peptideWT` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity_peptideWT | WT epitope that corresponds to ` NetMHCpan_bestAffinity_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestRank_rankWT | MHC I binding rank score of `NetMHCpan_bestRank_peptideWT` | MHC I binding with netMHCpan | -| NetMHCpan_bestRank_peptideWT | WT epitope that corresponds to `NetMHCpan_bestRank_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestRank9mer_rankWT | MHC I binding rank score of `NetMHCpan_bestRank9mer_peptideWT ` | MHC I binding with netMHCpan | -| NetMHCpan_bestRank9mer_peptideWT | WT epitope that corresponds to `NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_affinityWT | MHC I binding affinity of ` NetMHCpan_bestAffinity9mer_peptideWT ` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_rankWT | MHC I binding rank score of `NetMHCpan_bestAffinity9mer_peptideWT` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_peptideWT | WT epitope that corresponds to `NetMHCpan_bestAffinity9mer_peptide` | | -| PHBR_I | harmonic mean of minimal MHC I binding rank scores of all MHC I alleles of a patient | PHBR-I | -| NetMHCpan_bestAffinity9mer_positionMutation | indicates position of the mutation in ` NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_anchorMutated | mutation in ` NetMHCpan_bestRank9mer_peptide` in an anchor position (i.e. position 2 or 9) | anchor/non-anchor | -| NetMHCIIpan_bestRank_rank | minimal MHC II binding rank score over all neoepitope candidates (15mers) and all MHC II alleles | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestRank_peptide | neoepitope candidate sequence with minimal MHC II binding rank score | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestRank_allele | the MHC II isoform related to `NetMHCIIpan_bestRank_peptide` | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestAffinity_affinity | minimal MHC II binding affinity over all neoepitope candidates (15mers) and all MHC II alleles | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestAffinity_peptide | neoepitope candidate sequence with minimal MHC II binding affinity | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestAffinity_allele | the MHC II isoform related to ` NetMHCIIpan_bestAffinity_peptide` | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestRank_rankWT | minimal MHC II binding rank of `NetMHCIIpan_bestRank_peptideWT` | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestRank_peptideWT | WT epitope sequence (15mer) that corresponds to ` NetMHCIIpan_bestRank_peptide` | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestAffinity_affinityWT | minimal MHC II binding rank of `NetMHCIIpan_bestAffinity_peptideWT` | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestAffinity_peptideWT | WT epitope sequence (15mer) that corresponds to `NetMHCIIpan_bestAffinity_peptide` | MHC II binding with netMHCIIpan | -| PHBR_II | harmonic mean of minimal MHC II binding rank scores of all MHC II alleles of a patient | PHBR-II | -| Amplitude_MHCI_bestAffinity9mer | ratio of `NetMHCpan_bestAffinity9mer_affinity` and `NetMHCpan_bestAffinity9mer_affinityWT` | Recognition Potential | -| Amplitude_MHCI_bestAffinity | ratio of `NetMHCpan_bestAffinity_affinityWT` and `NetMHCpan_bestAffinity_affinity` | Generator rate | -| Amplitude_MHCII_bestRank | ratio of `NetMHCIIpan_bestRank_rank` and `NetMHCIIpan_bestRank_rankWT` | Generator rate | -| Pathogensimiliarity_MHCI_bestAffinity9mer | score representing the similarity of `NetMHCpan_bestAffinity9mer_peptide` to pathogen sequences in IEDB database | Recognition Potential | -| Pathogensimiliarity_MHCII_bestAffinity | score representing the similarity of `NetMHCIIpan_bestRank_peptide` to pathogen sequences in IEDB database | Recognition Potential | -| RecognitionPotential_MHCI_bestAffinity9mer | product of `Amplitude_MHCI_affinity_9mer` and `Pathogensimiliarity_MHCI_affinity_9mer` | Recognition Potential | -| DAI_MHCI_bestAffinity | difference of `NetMHCpan_bestAffinity_affinityWT` and `NetMHCpan_bestAffinity_affinity` | DAI | -| Classically_defined_neopeptide_MHCI | `NetMHCpan_bestAffinity_peptide`< 50 nM | Generator rate | -| Alternatively_defined_neopeptide_MHCI | `NetMHCpan_bestAffinity_peptide` < 5000 nM and `Amplitude_MHCI_bestAffinity` > 10 | Generator rate | -| Classically_defined_neopeptide_MHCII | `NetMHCIIpan_bestRank_rank` < 1 | Generator rate | -| Alternatively_defined_neopeptide_MHCII | `Best_rank_MHCII_score` < 4 and `Amplitude_MHCII_bestRank` < 2 | Generator rate | -| GeneratorRate_CDN_MHCI | number of neoepitope candidates with MHC I binding affinity < 50 nM per neoantigen canidate | Generator rate | -| GeneratorRate_ADN_MHCI | number of neoepitope candidates with MHC I binding affinity < 5000 nM per neoantigen canidate 10x better affinity in comparison to corresponding WT peptide | Generator rate | -| GeneratorRate_MHCI | sum of `GeneratorRate_CDN_MHCI` and `GeneratorRate_ADN_MHCI` | Generator rate | -| GeneratorRate_CDN_MHCII | number of neoepitope candidates with MHC II binding rank score < 1 per neoantigen canidate | Generator rate | -| GeneratorRate_ADN_MHCII | number of neoepitope candidates with MHC II binding rank score < 4 per neoantigen candidate 4x better rank in comparison to corresponding WT peptide | Generator rate | -| GeneratorRate_MHCII | sum of `GeneratorRate_CDN_MHCII` and `GeneratorRate_ADN_MHCII` | Generator rate | -| Tcell_predictor | output score of T cell predictor model | Tcell predictor | -| ImprovedBinder_MHCI | ratio of `NetMHCpan_MHCI_rank_bestRankWT` and `NetMHCpan_MHCI_rank_bestRank` > 1.2 | self-similarity | -| Selfsimilarity_MHCI_conserved_binder | score representing the similarity between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptideWT` For conservered binder only | self-similarity | -| Selfsimilarity_MHCI | score representing the similarity between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptide` | self-similarity | -| Selfsimilarity_MHCII | score representing the similarity between `NetMHCIIpan_bestAffinity_peptide` and `NetMHCIIpan_bestAffinity_peptide` | self-similarity | -| Number_of_mismatches_MCHI | number of amino acids that do no match between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptideWT` | Priority score | -| Priority_score | combinatorial score of several features such as MHC binding, expression and VAF | Priority score | -| Neoag_immunogenicity | output score of neoag model | neoag | -| IEDB_Immunogenicity_MHCI | IEDB Immunogenicity score for ` NetMHCpan_bestAffinity_peptide` | IEDB Immunogenicity | -| IEDB_Immunogenicity_MHCII | IEDB Immunogenicity score for `NetMHCIIpan_bestAffinity_peptide` | IEDB Immunogenicity | -| MixMHCpred_bestScore_peptide | MHC class I neoepitope candidate sequence with maximum MixMHCpred score over all neoepitope canidates (8-11mers) and MHC I alleles | MixMHCpred | -| MixMHCpred_bestScore_score | maximum MixMHCpred score over all neoepitope canidates (8-11mers) and MHC I alleles | MixMHCpred | -| MixMHCpred_bestScore_rank | rank that corresponds to `MixMHCpred_bestScore_score` | MixMHCpred | -| MixMHCpred_bestScore_allele | the allele with maximum MixMHCpred score | MixMHCpred | -| MixMHC2pred_bestRank_peptide | MHC class II neoepitope candidate sequence with minimal MixMHC2pred score over all neoepitope canidates (13-18mers) and MHC II alleles | MixMHC2pred | -| MixMHC2pred_bestRank_rank | minimal MixMHC2pred score over all neoepitope canidates (13-18mers) and MHC II alleles | MixMHC2pred | -| MixMHC2pred_bestRank_allele | the MHC II isoform with minimum MixMHC2pred rank score | MixMHC2pred | -| Dissimilarity_MHCI | score reflecting the dissimilarity of `NetMHCpan_bestAffinity_peptide` to the self-proteome | dissimilarity | -| Dissimilarity_MHCII | score reflecting the dissimilarity of `NetMHCIIpan_bestAffinity_peptide` to the self-proteome | dissimilarity | -| Vaxrank_bindingScore | total binding score of vaxrank | vaxrank | -| Vaxrank_totalScore | product of total binding score and expression score. Originally, the root of the number of reads supporting the mutation are used in the original implementation. To simplify, the expression normalised to VAF is used. | vaxrank | -| PRIME_bestScore_allele | best predicted MHC allele by PRIME model | PRIME | -| PRIME_bestScore_peptide | best predicted neoepitope candidate by PRIME model | PRIME | -| PRIME_bestScore_rank | output rank score of PRIME model | PRIME | -| PRIME_bestScore_score | output score of PRIME model | PRIME | -| HexAlignmentScore_MHCI | the alignment score by HEX for `NetMHCpan_bestAffinity_peptide` | HEX | -| HexAlignmentScore_MHCII | the alignment score by HEX for ` NetMHCIIpan_bestAffinity_peptide` | HEX | +| Column name | Description | Feature group/ Paper | +|---------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------| +| dnaVariantAlleleFrequency | the variant allele frequency calculated from the DNA | - | +| mutatedXmer | the long mutated amino acid sequence | - | +| wildTypeXmer | the long non-mutated amino acid sequence. This field shall be empty for alternative neoantigen classes | - | +| patientIdentifier | the patient identifier | - | +| rnaExpression | the RNA expression. If expression was imputed, this will will be `imputedGeneExpression` | expression | +| imputedGeneExpression | median gene expression in the TCGA cohort of the tumor entity provided in the patient file. | expression | +| rnaVariantAlleleFrequency | the variant allele frequency calculated from the RNA | - | +| gene | the HGNC gene symbol | - | +| Expression_mutated_transcript | transcript expression normalized by the variant allele frequency of the mutation | expression | +| mutation_not_found_in_proteome | indicates if mutated amino acid sequence was not found in the WT proteome by exact search | Priority score | +| NetMHCpan_bestRank_rank | minimal MHC I binding rank score over all neoepitope candidates (8-11mers) and MHC I alleles | MHC I binding with netMHCpan | +| NetMHCpan_bestRank_peptide | neoepitope candidate sequence with minimal MHC I binding rank score | MHC I binding with netMHCpan | +| NetMHCpan_bestRank_allele | the MHC I allele related to `NetMHCpan_bestRank_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_affinity | minimal MHC I binding affinity over all neoepitope candidates (8-11mers) and MHC I alleles | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_peptide | neoepitope candidate sequence with minimal MHC I binding affinity | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_allele | the MHC I allele related to `NetMHCpan_bestAffinity_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestRank9mer_rank | minimal MHC I binding rank score over all neoepitope candidates (9mers only) and MHC I alleles | MHC I binding with netMHCpan | +| NetMHCpan_bestRank9mer_peptide | neoepitope candidate sequence (9mer) with minimal MHC I binding rank score | MHC I binding with netMHCpan | +| NetMHCpan_bestRank9mer_allele | the MHC I allele related to `NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_affinity | minimal MHC I binding affinity over all neoepitope candidates (9mers) and MHC I alleles | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_allele | the MHC I allele related to `NetMHCpan_bestAffinity9mer_peptide ` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_peptide | neoepitope candidate sequence (9mer) with minimal MHC I binding affinity | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_affinityWT | MHC I binding affinity of `NetMHCpan_bestAffinity_peptideWT` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_peptideWT | WT epitope that corresponds to `NetMHCpan_bestAffinity_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestRank_rankWT | MHC I binding rank score of `NetMHCpan_bestRank_peptideWT` | MHC I binding with netMHCpan | +| NetMHCpan_bestRank_peptideWT | WT epitope that corresponds to `NetMHCpan_bestRank_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestRank9mer_rankWT | MHC I binding rank score of `NetMHCpan_bestRank9mer_peptideWT ` | MHC I binding with netMHCpan | +| NetMHCpan_bestRank9mer_peptideWT | WT epitope that corresponds to `NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_affinityWT | MHC I binding affinity of ` NetMHCpan_bestAffinity9mer_peptideWT ` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_peptideWT | WT epitope that corresponds to `NetMHCpan_bestAffinity9mer_peptide` | | +| PHBR_I | harmonic mean of minimal MHC I binding rank scores of all MHC I alleles of a patient | PHBR-I | +| NetMHCpan_bestAffinity9mer_positionMutation | indicates position of the mutation in ` NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_anchorMutated | mutation in `NetMHCpan_bestRank9mer_peptide` in an anchor position (i.e. position 2 or 9) | anchor/non-anchor | +| NetMHCIIpan_bestRank_rank | minimal MHC II binding rank score over all neoepitope candidates (15mers) and all MHC II alleles | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestRank_peptide | neoepitope candidate sequence with minimal MHC II binding rank score | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestRank_allele | the MHC II isoform related to `NetMHCIIpan_bestRank_peptide` | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestAffinity_affinity | minimal MHC II binding affinity over all neoepitope candidates (15mers) and all MHC II alleles | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestAffinity_peptide | neoepitope candidate sequence with minimal MHC II binding affinity | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestAffinity_allele | the MHC II isoform related to `NetMHCIIpan_bestAffinity_peptide` | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestRank_rankWT | minimal MHC II binding rank of `NetMHCIIpan_bestRank_peptideWT` | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestRank_peptideWT | WT epitope sequence (15mer) that corresponds to ` NetMHCIIpan_bestRank_peptide` | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestAffinity_affinityWT | minimal MHC II binding rank of `NetMHCIIpan_bestAffinity_peptideWT` | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestAffinity_peptideWT | WT epitope sequence (15mer) that corresponds to `NetMHCIIpan_bestAffinity_peptide` | MHC II binding with netMHCIIpan | +| PHBR_II | harmonic mean of minimal MHC II binding rank scores of all MHC II alleles of a patient | PHBR-II | +| Amplitude_MHCI_bestAffinity9mer | ratio of `NetMHCpan_bestAffinity9mer_affinity` and `NetMHCpan_bestAffinity9mer_affinityWT` | Recognition Potential | +| Amplitude_MHCI_bestAffinity | ratio of `NetMHCpan_bestAffinity_affinityWT` and `NetMHCpan_bestAffinity_affinity` | Generator rate | +| Amplitude_MHCII_bestRank | ratio of `NetMHCIIpan_bestRank_rank` and `NetMHCIIpan_bestRank_rankWT` | Generator rate | +| Pathogensimiliarity_MHCI_bestAffinity9mer | score representing the similarity of `NetMHCpan_bestAffinity9mer_peptide` to pathogen sequences in IEDB database | Recognition Potential | +| Pathogensimiliarity_MHCII_bestAffinity | score representing the similarity of `NetMHCIIpan_bestRank_peptide` to pathogen sequences in IEDB database | Recognition Potential | +| RecognitionPotential_MHCI_bestAffinity9mer | product of `Amplitude_MHCI_affinity_9mer` and `Pathogensimiliarity_MHCI_affinity_9mer` | Recognition Potential | +| DAI_MHCI_bestAffinity | difference of `NetMHCpan_bestAffinity_affinityWT` and `NetMHCpan_bestAffinity_affinity` | DAI | +| Classically_defined_neopeptide_MHCI | `NetMHCpan_bestAffinity_peptide`< 50 nM | Generator rate | +| Alternatively_defined_neopeptide_MHCI | `NetMHCpan_bestAffinity_peptide` < 5000 nM and `Amplitude_MHCI_bestAffinity` > 10 | Generator rate | +| Classically_defined_neopeptide_MHCII | `NetMHCIIpan_bestRank_rank` < 1 | Generator rate | +| Alternatively_defined_neopeptide_MHCII | `Best_rank_MHCII_score` < 4 and `Amplitude_MHCII_bestRank` < 2 | Generator rate | +| GeneratorRate_CDN_MHCI | number of neoepitope candidates with MHC I binding affinity < 50 nM per neoantigen canidate | Generator rate | +| GeneratorRate_ADN_MHCI | number of neoepitope candidates with MHC I binding affinity < 5000 nM per neoantigen canidate 10x better affinity in comparison to corresponding WT peptide | Generator rate | +| GeneratorRate_MHCI | sum of `GeneratorRate_CDN_MHCI` and `GeneratorRate_ADN_MHCI` | Generator rate | +| GeneratorRate_CDN_MHCII | number of neoepitope candidates with MHC II binding rank score < 1 per neoantigen canidate | Generator rate | +| GeneratorRate_ADN_MHCII | number of neoepitope candidates with MHC II binding rank score < 4 per neoantigen candidate 4x better rank in comparison to corresponding WT peptide | Generator rate | +| GeneratorRate_MHCII | sum of `GeneratorRate_CDN_MHCII` and `GeneratorRate_ADN_MHCII` | Generator rate | +| Tcell_predictor | output score of T cell predictor model | Tcell predictor | +| ImprovedBinder_MHCI | ratio of `NetMHCpan_MHCI_rank_bestRankWT` and `NetMHCpan_MHCI_rank_bestRank` > 1.2 | self-similarity | +| Selfsimilarity_MHCI_conserved_binder | score representing the similarity between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptideWT` For conservered binder only | self-similarity | +| Selfsimilarity_MHCI | score representing the similarity between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptide` | self-similarity | +| Selfsimilarity_MHCII | score representing the similarity between `NetMHCIIpan_bestAffinity_peptide` and `NetMHCIIpan_bestAffinity_peptide` | self-similarity | +| Number_of_mismatches_MCHI | number of amino acids that do no match between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptideWT` | Priority score | +| Priority_score | combinatorial score of several features such as MHC binding, expression and VAF | Priority score | +| Neoag_immunogenicity | output score of neoag model | neoag | +| IEDB_Immunogenicity_MHCI | IEDB Immunogenicity score for `NetMHCpan_bestAffinity_peptide` | IEDB Immunogenicity | +| IEDB_Immunogenicity_MHCII | IEDB Immunogenicity score for `NetMHCIIpan_bestAffinity_peptide` | IEDB Immunogenicity | +| MixMHCpred_bestScore_peptide | MHC class I neoepitope candidate sequence with maximum MixMHCpred score over all neoepitope canidates (8-11mers) and MHC I alleles | MixMHCpred | +| MixMHCpred_bestScore_score | maximum MixMHCpred score over all neoepitope canidates (8-11mers) and MHC I alleles | MixMHCpred | +| MixMHCpred_bestScore_rank | rank that corresponds to `MixMHCpred_bestScore_score` | MixMHCpred | +| MixMHCpred_bestScore_allele | the allele with maximum MixMHCpred score | MixMHCpred | +| MixMHC2pred_bestRank_peptide | MHC class II neoepitope candidate sequence with minimal MixMHC2pred score over all neoepitope canidates (13-18mers) and MHC II alleles | MixMHC2pred | +| MixMHC2pred_bestRank_rank | minimal MixMHC2pred score over all neoepitope canidates (13-18mers) and MHC II alleles | MixMHC2pred | +| MixMHC2pred_bestRank_allele | the MHC II isoform with minimum MixMHC2pred rank score | MixMHC2pred | +| Dissimilarity_MHCI | score reflecting the dissimilarity of `NetMHCpan_bestAffinity_peptide` to the self-proteome | dissimilarity | +| Dissimilarity_MHCII | score reflecting the dissimilarity of `NetMHCIIpan_bestAffinity_peptide` to the self-proteome | dissimilarity | +| Vaxrank_bindingScore | total binding score of vaxrank | vaxrank | +| Vaxrank_totalScore | product of total binding score and expression score. Originally, the root of the number of reads supporting the mutation are used in the original implementation. To simplify, the expression normalised to VAF is used. | vaxrank | +| PRIME_bestScore_allele | best predicted MHC allele by PRIME model | PRIME | +| PRIME_bestScore_peptide | best predicted neoepitope candidate by PRIME model | PRIME | +| PRIME_bestScore_rank | output rank score of PRIME model | PRIME | +| PRIME_bestScore_score | output score of PRIME model | PRIME | +| HexAlignmentScore_MHCI | the alignment score by HEX for `NetMHCpan_bestAffinity_peptide` | HEX | +| HexAlignmentScore_MHCII | the alignment score by HEX for `NetMHCIIpan_bestAffinity_peptide` | HEX | In addition, all logging output is appended to a log file with the suffix diff --git a/docs/source/03_03_usage.md b/docs/source/03_03_usage.md index ba9db639..2604c7e8 100755 --- a/docs/source/03_03_usage.md +++ b/docs/source/03_03_usage.md @@ -15,7 +15,7 @@ neofox --input-file neoantigens_candidates.tsv \ [--output-prefix out_prefix] \ [--organism human|mouse] \ [--rank-mhci-threshold 2.0] \ - [--rank-mhcii-threshold 4.0] \ + [--rank-mhcii-threshold 5.0] \ [--num-cpus] \ [--config] \ [--patient-id] \ diff --git a/docs/source/05_models.md b/docs/source/05_models.md index 6f257bc6..5d475081 100644 --- a/docs/source/05_models.md +++ b/docs/source/05_models.md @@ -195,7 +195,6 @@ The metadata required for analysis for a given patient + its patient identifier | Field | Type | Label | Description | | ----- | ---- | ----- | ----------- | | identifier | [string](#string) | | Patient identifier | -| isRnaAvailable | [bool](#bool) | | Is RNA expression available? | | tumorType | [string](#string) | | Tumor entity in TCGA study abbrevation style as described here: https://gdc.cancer.gov/resources-tcga-users/tcga-code-tables/tcga-study-abbreviations | | mhc1 | [Mhc1](#neoantigen.Mhc1) | repeated | MHC I classic molecules | | mhc2 | [Mhc2](#neoantigen.Mhc2) | repeated | MHC II classic molecules | diff --git a/gpl-v3.tmpl b/gpl-v3.tmpl old mode 100644 new mode 100755 diff --git a/neofox/MHC_predictors/netmhcpan/combine_netmhcpan_pred_multiple_binders.py b/neofox/MHC_predictors/netmhcpan/combine_netmhcpan_pred_multiple_binders.py index a6da0863..3d388757 100755 --- a/neofox/MHC_predictors/netmhcpan/combine_netmhcpan_pred_multiple_binders.py +++ b/neofox/MHC_predictors/netmhcpan/combine_netmhcpan_pred_multiple_binders.py @@ -190,7 +190,7 @@ def get_annotations(self) -> List[Annotation]: if self.best_epitope_by_rank: annotations.extend([ AnnotationFactory.build_annotation( - value=self.best_epitope_by_rank.rank_mutated, name="NetMHCpan_MHCI_bestRank_rank" + value=self.best_epitope_by_rank.rank_mutated, name="NetMHCpan_bestRank_rank" ), AnnotationFactory.build_annotation( value=self.best_epitope_by_rank.mutated_peptide, diff --git a/neofox/__init__.py b/neofox/__init__.py index 7f60eabd..1c226185 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,8 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.0.4" - +VERSION = "1.1.0b9" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" diff --git a/neofox/annotator/abstract_annotator.py b/neofox/annotator/abstract_annotator.py index fb08f2ff..20569016 100644 --- a/neofox/annotator/abstract_annotator.py +++ b/neofox/annotator/abstract_annotator.py @@ -53,7 +53,7 @@ def __init__( self.priority_score_calculator = PriorityScore() self.iedb_immunogenicity = IEDBimmunogenicity() self.amplitude = Amplitude() - self.hex = Hex(runner=self.runner, configuration=configuration, references=references) + self.hex = Hex(references=references) def get_additional_annotations_neoepitope_mhci( self, epitope: PredictedEpitope, neoantigen: Neoantigen = None) -> PredictedEpitope: diff --git a/neofox/command_line.py b/neofox/command_line.py index cd84df4a..204827e2 100755 --- a/neofox/command_line.py +++ b/neofox/command_line.py @@ -213,15 +213,11 @@ def _read_data(input_file, patients_data, mhc_database: MhcDatabase) -> Tuple[Li else: raise ValueError('Not supported input file extension: {}'.format(input_file)) - patients_dict : Dict[str, Patient] - patients_dict = {p.identifier: p for p in patients} - - for n in neoantigens: - patient = patients_dict.get(n.patient_identifier) - if not patient.is_rna_available: - # removes RNA vaf if indicated in patient that this information is no good - # iCam legacy - n.rna_variant_allele_frequency = None + ### Van -- check if patient candidates exist in the patient data file + neoantigens_patient_ids = set(i['patientIdentifier'] for i in neoantigens) + patient_ids = set(j['identifier'] for j in patients) + if neoantigens_patient_ids.difference(patient_ids) > 0: + raise ValueError('%s patient candidate does not exist in the patient data file.' % neoantigens_patient_ids) return neoantigens, patients @@ -386,16 +382,6 @@ def _read_data_epitopes( else: raise ValueError('Not supported input file extension: {}'.format(input_file)) - patients_dict : Dict[str, Patient] - patients_dict = {p.identifier: p for p in patients} - - for n in neoepitopes: - patient = patients_dict.get(n.patient_identifier) - if patient is not None and not patient.is_rna_available: - # removes RNA vaf if indicated in patient that this information is no good - # iCam legacy - n.rna_variant_allele_frequency = None - return neoepitopes, patients diff --git a/neofox/model/conversion.py b/neofox/model/conversion.py index f57f6c56..757efacf 100755 --- a/neofox/model/conversion.py +++ b/neofox/model/conversion.py @@ -111,7 +111,6 @@ def parse_patients_file(patients_file: str, mhc_database: MhcDatabase) -> List[P patient_dict = row.to_dict() patient = PatientFactory.build_patient( identifier=patient_dict.get("identifier"), - is_rna_available=patient_dict.get("isRnaAvailable", False), tumor_type=patient_dict.get("tumorType"), mhc_alleles=patient_dict.get("mhcIAlleles", []), mhc2_alleles=patient_dict.get("mhcIIAlleles", []), diff --git a/neofox/model/factories.py b/neofox/model/factories.py index b1da0522..6b6ce7ff 100755 --- a/neofox/model/factories.py +++ b/neofox/model/factories.py @@ -173,11 +173,10 @@ def build_neoepitope(mutated_peptide=None, wild_type_peptide=None, patient_ident class PatientFactory(object): @staticmethod - def build_patient(identifier, is_rna_available=False, tumor_type=None, mhc_alleles: List[str] = [], + def build_patient(identifier, tumor_type=None, mhc_alleles: List[str] = [], mhc2_alleles: List[str] = [], mhc_database: MhcDatabase =None): patient = Patient( identifier=identifier, - is_rna_available=is_rna_available, tumor_type=tumor_type, mhc1=MhcFactory.build_mhc1_alleles(mhc_alleles, mhc_database), mhc2=MhcFactory.build_mhc2_alleles(mhc2_alleles, mhc_database) diff --git a/neofox/model/mhc_parser.py b/neofox/model/mhc_parser.py index 1d3151e2..b6082516 100644 --- a/neofox/model/mhc_parser.py +++ b/neofox/model/mhc_parser.py @@ -38,7 +38,7 @@ ) HLA_DR_MOLECULE_PATTERN = re.compile(r"(?:HLA-)?(DRB1[\*|_]?[0-9]{2,}[:|_]?[0-9]{2,})") -H2_ALLELE_PATTERN = re.compile(r"(H2K|H2D|H2L|H2A|H2E)([a-z][0-9]?)") +H2_ALLELE_PATTERN = re.compile(r"(H2-?[KDLAE])([a-z][0-9]?)") H2_NETMHCPAN_ALLELE_PATTERN = re.compile(r"H-2-I?(K|D|L|A|E)([a-z][0-9]?)") H2_MOLECULE_PATTERN = re.compile(r"(H2A|H2E)([a-z][0-9]?)") diff --git a/neofox/model/models.md b/neofox/model/models.md index 6f257bc6..5d475081 100644 --- a/neofox/model/models.md +++ b/neofox/model/models.md @@ -195,7 +195,6 @@ The metadata required for analysis for a given patient + its patient identifier | Field | Type | Label | Description | | ----- | ---- | ----- | ----------- | | identifier | [string](#string) | | Patient identifier | -| isRnaAvailable | [bool](#bool) | | Is RNA expression available? | | tumorType | [string](#string) | | Tumor entity in TCGA study abbrevation style as described here: https://gdc.cancer.gov/resources-tcga-users/tcga-code-tables/tcga-study-abbreviations | | mhc1 | [Mhc1](#neoantigen.Mhc1) | repeated | MHC I classic molecules | | mhc2 | [Mhc2](#neoantigen.Mhc2) | repeated | MHC II classic molecules | diff --git a/neofox/model/neoantigen.proto b/neofox/model/neoantigen.proto index 757c62c2..572fad93 100755 --- a/neofox/model/neoantigen.proto +++ b/neofox/model/neoantigen.proto @@ -78,21 +78,17 @@ message Patient { */ string identifier = 1; /** - Is RNA expression available? - */ - bool isRnaAvailable = 2; - /** Tumor entity in TCGA study abbrevation style as described here: https://gdc.cancer.gov/resources-tcga-users/tcga-code-tables/tcga-study-abbreviations */ - string tumorType = 3; + string tumorType = 2; /** MHC I classic molecules */ - repeated Mhc1 mhc1 = 4; + repeated Mhc1 mhc1 = 3; /** MHC II classic molecules */ - repeated Mhc2 mhc2 = 5; + repeated Mhc2 mhc2 = 4; } /** diff --git a/neofox/model/neoantigen.py b/neofox/model/neoantigen.py index a0b253d3..b4b925fd 100755 --- a/neofox/model/neoantigen.py +++ b/neofox/model/neoantigen.py @@ -120,16 +120,14 @@ class Patient(betterproto.Message): # *Patient identifier identifier: str = betterproto.string_field(1) - # *Is RNA expression available? - is_rna_available: bool = betterproto.bool_field(2) # *Tumor entity in TCGA study abbrevation style as described here: # https://gdc.cancer.gov/resources-tcga-users/tcga-code-tables/tcga-study- # abbreviations - tumor_type: str = betterproto.string_field(3) + tumor_type: str = betterproto.string_field(2) # *MHC I classic molecules - mhc1: List["Mhc1"] = betterproto.message_field(4) + mhc1: List["Mhc1"] = betterproto.message_field(3) # *MHC II classic molecules - mhc2: List["Mhc2"] = betterproto.message_field(5) + mhc2: List["Mhc2"] = betterproto.message_field(4) @dataclass diff --git a/neofox/neofox.py b/neofox/neofox.py index c805393b..40a698e2 100755 --- a/neofox/neofox.py +++ b/neofox/neofox.py @@ -110,10 +110,6 @@ def __init__( for neoantigen in self.neoantigens: expression_per_patient[neoantigen.patient_identifier].append(neoantigen.rna_expression) - for patient in self.patients: - self.patients[patient].is_rna_available = all(e is not None for e in - expression_per_patient[self.patients[patient].identifier]) - # only performs the expression imputation for humans if self.reference_folder.organism == ORGANISM_HOMO_SAPIENS: # impute expresssion from TCGA, ONLY if isRNAavailable = False for given patient, @@ -137,7 +133,7 @@ def _conditional_expression_imputation(self) -> List[Neoantigen]: gene_expression = expression_annotator.get_gene_expression_annotation( gene_name=neoantigen.gene, tcga_cohort=patient.tumor_type ) - if not patient.is_rna_available and patient.tumor_type is not None and patient.tumor_type != "": + if expression_value is None and patient.tumor_type is not None and patient.tumor_type != "": expression_value = gene_expression neoantigen_transformed.rna_expression = expression_value neoantigen.imputed_gene_expression = gene_expression diff --git a/neofox/neofox_epitope.py b/neofox/neofox_epitope.py index 26433cb2..37d7e79a 100755 --- a/neofox/neofox_epitope.py +++ b/neofox/neofox_epitope.py @@ -211,8 +211,6 @@ def _conditional_expression_imputation(self) -> List[PredictedEpitope]: neoepitope_transformed = neoepitope gene_expression = expression_annotator.get_gene_expression_annotation( gene_name=neoepitope.gene, tcga_cohort=patient.tumor_type) - if not patient.is_rna_available and patient.tumor_type is not None and patient.tumor_type != "": - neoepitope_transformed.rna_expression = gene_expression neoepitope.imputed_gene_expression = gene_expression neoepitopes_transformed.append(neoepitope_transformed) else: diff --git a/neofox/published_features/hex/BLOSUM62.rda b/neofox/published_features/hex/BLOSUM62.rda deleted file mode 100644 index 88991e871ceb3b9b95b660715aee3ea33548af20..0000000000000000000000000000000000000000 GIT binary patch literal 0 HcmV?d00001 literal 532 zcmV+v0_*)kT4*^jL0KkKS>d~Rg8%}F|A7Dg$RGd^5dc5`|L~?GC;$Klzyfl(bT9~~ zrlUqpLlL6_10cd=(@SKm$MkWElW6P-&_oKr|XO28=<8f@EN72vUke)Bpg} zO#o=xjj6Oi&Hz&D;2|6;AaE6FL%hZw_mEl2(+rY9*Z~?c8Fc1_C0JVt0o7w;!I1cJbV`~ zD4NirKo2LA5qsBWL{q~cY=z!xbDr~*{F_gi^*IlrwELS*V`;S7a~qC>oas7E=dtym z9Egkv2J4m%Ii%H))fVXqMos%I&KV$U)*l1XP+GSZkq~8B{!05>&L(E|M8E6sar~5>n1Jsn#-ES zcVTNy7!UVnmKKHO?7c^a9BjD&~&S8LD@}l%(Ds% z8pshRYYMEWkPB>#5H6EqnXsg2M3JJdO|p>$U}Q2(d#N-r*0#xqkc1AA266FR-xy4! Wj<*rn4T}U%_`8xR!i0wn+sqjCE8x`t diff --git a/neofox/published_features/hex/EPItOMe_modified.R b/neofox/published_features/hex/EPItOMe_modified.R deleted file mode 100644 index bdda41f9..00000000 --- a/neofox/published_features/hex/EPItOMe_modified.R +++ /dev/null @@ -1,309 +0,0 @@ -#' Get position specific weights, higher scores for the mid bases compared to tails. -#' -#' Compute the position specific scores for the amino acid bases with heavier weight for the middle bases -#' and lower score for bases towards the edges. Scores are a function of amino acid bases vector length -#' and the magnitude of score elevation by base distance from edges, bases on the third quartile of edges -#' are simplified to magnitude of 1 beginning from 1. -#' -#' @param x A character vector of Amino Acid bases. -#' @param mag Numeric value to use for seq() function to create distant sequence of weights -#' @return A numeric vector of scores equal to the length of the input vector of Amino Acids -#' @examples -#' \dontrun{ -#' get_pos_weights(x=AA.vec, mag=4) -#' } -#' @keywords internal -#' @export -get_pos_weights <- function(x, mag=4){ - posScore <- c() - xLen <- length(x) - xMid <- xLen/2 - if(xLen %% 2){ - #print("ODD?") - xMidCeil <- ceiling(xMid) - xMidScore <- xMidCeil*mag - posScore <- seq(1,xMidScore,mag) - posScore <- c(posScore, rev(posScore[1:length(posScore)-1])) - xTopFloor <- floor(xLen/3) - posScore[1:xTopFloor] <- 1:xTopFloor - xTail <- xLen-xTopFloor+1 - posScore[xTail:xLen] <- xTopFloor:1 - - }else{ - #print("EVEN?") - xMidScore <- xMid*mag - posScore <- seq(1,xMidScore,mag) - posScore <- c(posScore, rev(posScore)) - xTopFloor <- floor(xLen/3) - posScore[1:xTopFloor] <- 1:xTopFloor - xTail <- xLen-xTopFloor+1 - posScore[xTail:xLen] <- xTopFloor:1 - } - return(posScore) -} - -#' Alignment of singular epitope vector against a reference matrix of epitope, rows as epitopes with names and bases in -#' columns by position. -#' -#' Align the epitope sequence to the reference set of epitope sequences. Sequences are alignment globally -#' from end to end with matches assigned a postitive score as the position specific weight and mis-matches -#' are assigned a negative score as the negative of the position specific weight. Final alignment score is -#' the sum of all the positive and neagative scores from each base. This ensures that the alignment is matches -#' in the middle are scored higher than the alignments with mis-matches in the middle. -#' -#' @param x A character vector of Amino Acid bases. -#' @param ref A matrix of Amino Acid epitope sequences, epitopes with names in rows and bases by position in columns -#' @param mag Numeric value to use for seq() function to create distant sequence of weights -#' @return A numeric vecdtor of scores for x alignment to the each epitope in ref -#' @examples -#' \dontrun{ -#' align_to_ref_epitopes(x, ref, mag=4) -#' } -#' @keywords internal -#' @export -align_to_ref_epitopes <- - function(x, - ref, - mag = 4, - aln_matrix = "BLOSUM62") { - if (!exists(aln_matrix)) { - #data(aln_matrix) - data(aln_matrix, envir = environment()) - } - aln_matrix <- get(aln_matrix) - xPosWt <- get_pos_weights(x, mag) - #print(xPosWt) - xLen <- length(x) - - xAlnScoreVec <- c() - - if (is.matrix(ref)) { - refSeqCount <- nrow(ref) - } else if (is.character(ref)) { - refSeqCount <- 1 - } - else{ - stop("Unsupported object as ref. Must be either matrix or character") - } - - xAlnScoreVec <- apply(ref, 1, function(refSeq){ - xAlnMat <- diag(aln_matrix[x, refSeq]) - xAlnAmp <- xPosWt * xAlnMat - xAlnScore <- sum(xAlnAmp) - return(xAlnScore) - }) - names(xAlnScoreVec) <- rownames(ref) - - return(xAlnScoreVec) - } - -#' Read the epitope amino acid sequences from the fasta file -#' -#' Read epitope sequences from a fasta file, provided with the correct path to the file. -#' The read sequences are provided as a matrix with sequence in rows and each base of the -#' sequence as a column. -#' -#' @importFrom Biostrings readAAStringSet as.matrix -#' -#' @param iFile Path to a file containing epitope sequences in fasta format. -#' @return A matrix of Amino Acid epitope sequences, epitopes with names in rows and bases by position in columns -#' @examples -#' \dontrun{ -#' read_epitope_seq(iFile=input.file) -#' } -#' @keywords internal -#' @export -read_epitope_seq <- function(iFile){ - epitopes.AASet <- Biostrings::readAAStringSet(iFile) - epitopes.mat <- Biostrings::as.matrix(epitopes.AASet, use.names=T) - return(epitopes.mat) -} - - - -#' Convert the epitopes data frame to amino acid matrix with bases separated into columns -#' -#' Data frame of predict epitopes is converted to a matrix of epitope sequences by rows and their -#' bases in columns. -#' -#' @importFrom stats setNames -#' @importFrom Biostrings AAStringSet as.matrix -#' -#' @param sequence.name Name of the input protein sequence for predicting epitopes. -#' @param epitope.DF Data frame of the epitopes predicted by the IEDB server. -#' @return A matrix of Amino Acid epitope sequences, epitopes with names in rows and bases by position in columns -#' @examples -#' \dontrun{ -#' epitopeDF_to_AAmat(sequence.name, epitope.DF) -#' } -#' @keywords internal -#' @export -epitopeDF_to_AAmat <- function(sequence.name, epitope.DF){ - if(length(grep("#", sequence.name))>0){ - sequence.name <- gsub("#", "|", sequence.name) - } - res.vec <- stats::setNames(epitope.DF$peptide, paste0(sequence.name, "#", epitope.DF$start, "#", epitope.DF$end, "#", epitope.DF$percentile_rank, "#", epitope.DF$ann_ic50)) - res.AASet <- Biostrings::AAStringSet(res.vec) - res.mat <- Biostrings::as.matrix(res.AASet, use.names=T) - return(res.mat) -} - -#' Align set of query epitope sequences against set of reference epitope sequences -#' -#' Aligning set of query epitopes by multi-threaded parallel execution of align_to_red_epitopes() -#' function. The alignment score between all pairs of query and ref epitopes is reported as a matrix. -#' -#' @importFrom parallel makeCluster clusterExport parApply stopCluster -#' @importFrom doParallel registerDoParallel -#' -#' @param query.set A matrix of Amino Acid epitope sequences to align against the reference epitope sequences. -#' @param ref.set A matrix of Amino Acid epitope sequences, epitopes with names in rows and bases by position in columns. -#' @return A matrix of alignment scores for query epitopes against reference epitopes -#' @examples -#' \dontrun{ -#' align_sets(query.set, ref.set, env=NULL, num.cores=2) -#' } -#' @keywords internal -#' @export -# paralellisation was removed -align_sets <- function(query.set, ref.set, env=NULL, num.cores=2, aln_matrix="BLOSUM62"){ - if(!exists(aln_matrix)){ - print(paste0("Getting data:", aln_matrix)) - #data(aln_matrix) - data(aln_matrix, envir=environment()) - } - ref.set.name <- deparse(substitute(ref.set)) - ref.set.name <- strsplit(ref.set.name, "\\[")[[1]][1] - if(is.null(env)){ - env <- environment() - } - - # align the neoepitope sequence against a set of viral epitopes - alnRes <- align_to_ref_epitopes(query.set, ref=ref.set, aln_matrix=aln_matrix) - - return(alnRes) -} - -#' Get the pairs of query and reference epitopes with the best alignment score or above the -#' specified alignment score threshold -#' -#' Aligning set of query epitopes by multi-threaded parallel execution of align_to_red_epitopes() -#' function. The alignment score between all pairs of query and ref epitopes is reported as a matrix. -#' -#' @importFrom parallel makeCluster clusterExport parApply stopCluster -#' @importFrom doParallel registerDoParallel -#' -#' @param alnRes A matrix of alignment scores for query epitopes against reference epitopes. -#' @param query.set A matrix of Amino Acid epitope sequences to align against the reference epitope sequences. -#' @param ref.set A matrix of Amino Acid epitope sequences, epitopes with names in rows and bases by position in columns. -#' @param best A boolean flag to switch between selecting the pairs of epitopes with best alignment score or use the -#' input score value as a threshold. -#' @param score A numerical value to use as alignment score threshold. -#' @return A data frame of alignment result for the selected pairs of aligned epitopes -#' @examples -#' \dontrun{ -#' get_best_alignment(alnRes, query.set, ref.set, best=TRUE, score=NULL) -#' } -#' @keywords internal -#' @export -get_best_alignment <- function(alnRes, query.set, ref.set, best=TRUE, score=NULL){ - if(best==TRUE){ - bestAln <- which(alnRes==max(alnRes), arr.ind = TRUE) - }else if(is.null(score)){ - bestAln <- which(alnRes==max(alnRes), arr.ind = TRUE) - }else{ - bestAln <- which(alnRes>=score, arr.ind = TRUE) - } - - if(length(bestAln)==0){ - return(NULL) - } - - bestAlnCount <- nrow(bestAln) - resDF <- data.frame(query=character(), q_start=numeric(), q_end=numeric(), q_epitope_rank=numeric(), q_epitope_ic50=numeric(), q_epitope_seq=character(), ref=character(), r_start=numeric(), r_end=numeric(), r_epitope_rank=numeric(), r_epitope_ic50=numeric(), r_epitope_seq=character(), score=numeric(), stringsAsFactors=F) - for(i in 1:bestAlnCount){ - bestAlnRowName <- rownames(alnRes)[bestAln[i, "row"]] - bestAlnColName <- colnames(alnRes)[bestAln[i, "col"]] - bestAlnScore <- as.numeric(alnRes[bestAln[i,1],bestAln[i,2]]) - qSeq <- paste0(query.set[bestAlnColName,], collapse="") - rSeq <- paste0(ref.set[bestAlnRowName,], collapse="") - - bestAlnRowName.split <- strsplit(bestAlnRowName, "#")[[1]] - refName <- bestAlnRowName.split[1] - rStart <- as.numeric(bestAlnRowName.split[2]) - rEnd <- as.numeric(bestAlnRowName.split[3]) - rRank <- as.numeric(bestAlnRowName.split[4]) - rIC50 <- as.numeric(bestAlnRowName.split[5]) - - bestAlnColName.split <- strsplit(bestAlnColName, "#")[[1]] - queryName <- bestAlnColName.split[1] - qStart <- as.numeric(bestAlnColName.split[2]) - qEnd <- as.numeric(bestAlnColName.split[3]) - qRank <- as.numeric(bestAlnColName.split[4]) - qIC50 <- as.numeric(bestAlnColName.split[5]) - - tmpDF <- data.frame(query=queryName, q_start=qStart, q_end=qEnd, q_epitope_rank=qRank, q_epitope_ic50=qIC50, q_epitope_seq=qSeq, ref=refName, r_start=rStart, r_end=rEnd, r_epitope_rank=rRank, r_epitope_ic50=rIC50, r_epitope_seq=rSeq, score=bestAlnScore, stringsAsFactors=F) - resDF <- rbind(resDF, tmpDF) - } - return(resDF) -} - - -# B-score/ log-likelihood score -# this code was not working and was fixed -align_to_cpl <- function(x, ref){ - xlen <- length(x) - reflen <- nrow(ref) - - cpl <- matrix(nrow=xlen, ncol=20) - aacols <- Biostrings::AAString("ACDEFGHIKLMNPQRSTVWY") - - cpl <- sapply(1:20, function(j) { - sapply(1:xlen, function(xl) { - if (x[xl] == as.character(aacols[j])) { - 100 - } else{ - 1 - } - }) - }) - - colnames(cpl) <- c("A","C","D","E","F","G","H","I","K","L", - "M","N","P","Q","R","S","T","V","W","Y") - - score_vec <- c() - # scoring matrix - cpl <- log(cpl / rowSums(cpl)) - - score_vec <- apply(ref, 1, function(peptide){ - # this has been changed in comparison to the original version - # the loop over i was not over the length of the peptide - sum(sapply(1:xlen, function(l) { - sum(score <- - sapply(1:20, function(j) { - if (peptide[l] == as.character(aacols[j])) { - # if(peptide[i] == aacols[j]){ - cpl[l, j] - } else{ - NA - } - }), na.rm = T) - return(score) - }), na.rm = T) - }) - names(score_vec) <- rownames(ref) - return(score_vec) -} - -align_cpl_sets <- function(query.set, ref.set, env=NULL, num.cores=2, aln_matrix="BLOSUM62"){ - - ref.set.name <- deparse(substitute(ref.set)) - ref.set.name <- strsplit(ref.set.name, "\\[")[[1]][1] - if(is.null(env)){ - env <- environment() - } - cplRes <- align_to_cpl(query.set, ref.set) - - return(cplRes) -} - diff --git a/neofox/published_features/hex/hex.R b/neofox/published_features/hex/hex.R deleted file mode 100644 index 9d5553ee..00000000 --- a/neofox/published_features/hex/hex.R +++ /dev/null @@ -1,41 +0,0 @@ -require(Biostrings) - -args = commandArgs(trailingOnly=TRUE) - -epitope <- args[1] -path_virus_db <- args[2] -path_to_file <- args[3] - -source(paste0(path_to_file,"/EPItOMe_modified.R")) -load(paste0(path_to_file, "/BLOSUM62.rda")) - -aln_matrix <- "BLOSUM62" - -# neoepitope candidate sequence -qAASet <- AAStringSet(epitope) -qAASet <- Biostrings::as.matrix(qAASet, use.names=T) - -# virus database -#path_virus_db <- "/home/franlang/neofox_test/test_references_nets/iedb/IEDB.fasta" -rAASet <- readAAStringSet(path_virus_db, format="fasta") -# do filtering based on length of neoepitope sequence -rAASet <- rAASet[which(rAASet@ranges@width == length(qAASet))] -rms <- which(alphabetFrequency(rAASet)[,31] != 0) -# remove viral epitopes with non-canonical aa -if(length(rms) > 0){ - rAASet <- rAASet[-rms] -} -rAASet <- Biostrings::as.matrix(rAASet, use.names=T) - - -# alignment of viral and tumor epitopes -# alignment score -alnRes <- align_sets(query.set=qAASet, ref.set=rAASet, aln_matrix=aln_matrix) -# B-score -#cplRes <- align_cpl_sets(query.set=qAASet, ref.set=rAASet, aln_matrix=aln_matrix) - -#res <- c(unique(max(alnRes)), unique(max(cplRes))) -res <- unique(max(alnRes, na.rm = T)) -if(!is.numeric(res)){res = ""} - -cat(res) \ No newline at end of file diff --git a/neofox/published_features/hex/hex.py b/neofox/published_features/hex/hex.py index 116dfb5c..e1d42df9 100755 --- a/neofox/published_features/hex/hex.py +++ b/neofox/published_features/hex/hex.py @@ -18,33 +18,22 @@ # You should have received a copy of the GNU General Public License # along with this program. If not, see .# from typing import List -import os from neofox.model.neoantigen import Annotation, PredictedEpitope from neofox.model.factories import AnnotationFactory +from neofox.published_features.hex.pyhex import PyHex from neofox.references.references import ReferenceFolder class Hex(object): - def __init__(self, references: ReferenceFolder, runner, configuration): - """ - :type runner: neofox.helpers.runner.Runner - :type configuration: neofox.references.DependenciesConfiguration - """ - self.runner = runner - self.configuration = configuration + def __init__(self, references: ReferenceFolder): self.iedb_fasta = references.get_iedb_fasta() + self.pyhex = PyHex(self.iedb_fasta) def apply_hex(self, mut_peptide): """this function calls hex tool. this tool analyses the neoepitope candidate sequence for molecular mimicry to viral epitopes """ - my_path = os.path.abspath(os.path.dirname(__file__)) - tool_path = os.path.join(my_path, "hex.R") - cmd = [self.configuration.rscript, tool_path, mut_peptide, self.iedb_fasta, my_path] - output, _ = self.runner.run_command(cmd) - if output == "": - output = None - return output + return self.pyhex.run(mut_peptide) def get_annotation( self, mutated_peptide_mhci: PredictedEpitope, mutated_peptide_mhcii: PredictedEpitope) -> List[Annotation]: diff --git a/neofox/published_features/hex/pyhex.py b/neofox/published_features/hex/pyhex.py new file mode 100644 index 00000000..9db1e6d6 --- /dev/null +++ b/neofox/published_features/hex/pyhex.py @@ -0,0 +1,51 @@ +from math import ceil, floor + +from Bio import SeqIO +from Bio.Align import substitution_matrices +from Bio.Alphabet.IUPAC import ExtendedIUPACProtein + + +class PyHex: + + def __init__(self, iedb_fasta, magic_number=4): + self.iedb_sequences = self._read_fasta(iedb_fasta) + self.magic_number = magic_number + self.blosum = substitution_matrices.load("BLOSUM62") + + @staticmethod + def _read_fasta(fasta_file): + sequences = [] + # read fasta + with open(fasta_file, "r") as handle: + for record in SeqIO.parse(handle, "fasta"): + # include only records that do not contain non-standard amino acids + if not any([aa not in ExtendedIUPACProtein.letters for aa in record.seq]): + sequences.append(record) + return sequences + + def _align(self, sequence, mutated_sequence): + weights = self._get_sequence_weights(mutated_sequence) + score = sum([self.blosum[q, t] * w for q, t, w in zip(sequence, mutated_sequence, weights)]) + return score + + def _get_sequence_weights(self, mutated_sequence): + length_mutated_sequence = len(mutated_sequence) + mid_score = ceil(length_mutated_sequence / 2) * self.magic_number + weights = list(range(1, mid_score, self.magic_number)) + weights.extend(reversed(weights[0:floor(length_mutated_sequence / 2)])) + + top_floor = floor(length_mutated_sequence / 3) + weights[0:top_floor] = list(range(1, top_floor + 1)) + tail = length_mutated_sequence - top_floor + weights[tail:length_mutated_sequence] = list(reversed(range(1, top_floor + 1))) + + return weights + + def run(self, mutated_sequence): + # excludes sequences that have different length than the mutated sequence + sequences = [s for s in self.iedb_sequences if len(s.seq) == len(mutated_sequence)] + # align each of the sequences + alignment_scores = [self._align(s.seq, mutated_sequence) for s in sequences] + # gets the best score of all the alignments + best_score = max(alignment_scores) + return best_score diff --git a/neofox/references/install_r_dependencies.R b/neofox/references/install_r_dependencies.R index 7b906a14..2d8f6bc4 100644 --- a/neofox/references/install_r_dependencies.R +++ b/neofox/references/install_r_dependencies.R @@ -1,9 +1,3 @@ -install.packages("lattice", repo="http://cran.rstudio.com/") -install.packages("ggplot2", repo="http://cran.rstudio.com/") install.packages("caret", repo="http://cran.rstudio.com/") install.packages("Peptides", repo="http://cran.rstudio.com/") install.packages("doParallel", repo="http://cran.rstudio.com/") -install.packages("gbm", repo="http://cran.rstudio.com/") -if (!requireNamespace("BiocManager", quietly = TRUE)) - install.packages("BiocManager") -BiocManager::install("Biostrings") \ No newline at end of file diff --git a/neofox/tests/integration_tests/test_hex.py b/neofox/tests/integration_tests/test_hex.py index d6a24a96..7684b0b6 100755 --- a/neofox/tests/integration_tests/test_hex.py +++ b/neofox/tests/integration_tests/test_hex.py @@ -22,7 +22,7 @@ from neofox.helpers.runner import Runner import neofox.tests.integration_tests.integration_test_tools as integration_test_tools - +from neofox.published_features.hex.pyhex import PyHex class TestHex(TestCase): @@ -30,15 +30,24 @@ def setUp(self): self.references, self.configuration = integration_test_tools.load_references() self.runner = Runner() - def test_hex(self): - res = Hex( - runner=self.runner, configuration=self.configuration, references=self.references - ).apply_hex( - mut_peptide="FGLAIDVDD" - ) - logger.info(res) - self.assertEqual(float(res), 148) + res = Hex(references=self.references).apply_hex(mut_peptide="FGLAIDVDD") + self.assertEqual(int(res), 148) + + def test_pyhex(self): + pyhex = PyHex(iedb_fasta=self.references.get_iedb_fasta()) + res = pyhex.run("FGLAIDVDD") + self.assertEqual(res, 148) + + def test_comparison(self): + for i in range(10): + for k in range(9, 30): + peptide = integration_test_tools.get_random_kmer(k=k) + logger.info(peptide) + res = Hex(references=self.references).apply_hex(mut_peptide=peptide) + pyhex = PyHex(iedb_fasta=self.references.get_iedb_fasta()) + res_pyhex = pyhex.run(peptide) + self.assertEqual(float(res), res_pyhex, "Peptide: {}".format(peptide)) diff --git a/neofox/tests/integration_tests/test_neofox.py b/neofox/tests/integration_tests/test_neofox.py index 585f91d3..4d885ec4 100755 --- a/neofox/tests/integration_tests/test_neofox.py +++ b/neofox/tests/integration_tests/test_neofox.py @@ -345,8 +345,6 @@ def test_neofox_without_mhc1(self): def test_gene_expression_imputation(self): neoantigens, patients = self._get_test_data() - for p in patients: - p.is_rna_available = False neofox = NeoFox( neoantigens=neoantigens, patients=patients, diff --git a/neofox/tests/synthetic_data/factories.py b/neofox/tests/synthetic_data/factories.py old mode 100644 new mode 100755 index 233cf00e..0af11d2e --- a/neofox/tests/synthetic_data/factories.py +++ b/neofox/tests/synthetic_data/factories.py @@ -78,7 +78,6 @@ def patient(self) -> Patient: try: patient = Patient( identifier=self.generator.unique.uuid4(), - is_rna_available=True, tumor_type=self.random_elements(self.available_tumor_types, length=1)[0], # by setting unique=True we enforce that all patients are heterozygous mhc1=MhcFactory.build_mhc1_alleles( diff --git a/neofox/tests/unit_tests/test_model_converter.py b/neofox/tests/unit_tests/test_model_converter.py index a69e1bf4..a79446b8 100755 --- a/neofox/tests/unit_tests/test_model_converter.py +++ b/neofox/tests/unit_tests/test_model_converter.py @@ -193,7 +193,6 @@ def test_patients_csv_file2model(self): self.assertEqual( 9, len([a for m in patients[0].mhc2 for g in m.genes for a in g.alleles]) ) - self.assertEqual(patients[0].is_rna_available, False) def test_patients_without_mhc2(self): patients_file = pkg_resources.resource_filename( @@ -208,7 +207,6 @@ def test_patients_without_mhc2(self): self.assertEqual(3, len(patients[0].mhc1)) self.assertEqual(6, len([a for m in patients[0].mhc1 for a in m.alleles])) self.assertEqual(0, len(patients[0].mhc2)) - self.assertEqual(patients[0].is_rna_available, False) def test_patients_csv_file2model_mouse(self): patients_file = pkg_resources.resource_filename( @@ -226,7 +224,6 @@ def test_patients_csv_file2model_mouse(self): self.assertEqual( 3, len([a for m in patients[0].mhc2 for g in m.genes for a in g.alleles]) ) - self.assertEqual(patients[0].is_rna_available, False) def test_patients_csv_file2model2(self): patients_file = pkg_resources.resource_filename( @@ -244,7 +241,6 @@ def test_patients_csv_file2model2(self): self.assertEqual( 9, len([a for m in patients[0].mhc2 for g in m.genes for a in g.alleles]) ) - self.assertEqual(patients[0].is_rna_available, True) def test_patients_csv_file2model3(self): patients_file = pkg_resources.resource_filename( @@ -269,7 +265,6 @@ def test_patients_csv_file2model3(self): "HLA-DQA1*04:01" in [a.name for m in patients[0].mhc2 for g in m.genes for a in g.alleles] ) - self.assertTrue(patients[0].is_rna_available) def test_patients_csv_file2model_without_mhc1(self): patients_file = pkg_resources.resource_filename( @@ -287,7 +282,6 @@ def test_patients_csv_file2model_without_mhc1(self): self.assertEqual( 9, len([a for m in patients[0].mhc2 for g in m.genes for a in g.alleles]) ) - self.assertEqual(patients[0].is_rna_available, True) def test_patients_csv_file2model_without_mhc2(self): patients_file = pkg_resources.resource_filename( diff --git a/neofox/tests/unit_tests/test_neofox.py b/neofox/tests/unit_tests/test_neofox.py index ebf62169..f93f5d84 100755 --- a/neofox/tests/unit_tests/test_neofox.py +++ b/neofox/tests/unit_tests/test_neofox.py @@ -191,11 +191,12 @@ def test_with_expression_imputation(self): reference_folder=FakeReferenceFolder(), configuration=FakeDependenciesConfiguration(), ) - for neoantigen in original_neoantigens: - for neoantigen_imputed in neofox_runner.neoantigens: - self.assertFalse( - neoantigen.rna_expression == neoantigen_imputed.rna_expression - ) + for neoantigen, neoantigen_imputed in zip(original_neoantigens, neofox_runner.neoantigens): + self.assertIsNotNone(neoantigen_imputed.imputed_gene_expression) + if neoantigen.rna_expression is None: + self.assertNotEqual(neoantigen.rna_expression, neoantigen_imputed.rna_expression) + else: + self.assertEqual(neoantigen.rna_expression, neoantigen_imputed.rna_expression) def _get_test_neoantigen(self): return Neoantigen( @@ -207,7 +208,7 @@ def _get_test_neoantigen(self): ) def _get_test_patient(self): - return Patient(identifier="12345", is_rna_available=True) + return Patient(identifier="12345") if __name__ == "__main__": diff --git a/neofox/tests/unit_tests/test_validation.py b/neofox/tests/unit_tests/test_validation.py old mode 100644 new mode 100755 index 39f38d5b..311c3159 --- a/neofox/tests/unit_tests/test_validation.py +++ b/neofox/tests/unit_tests/test_validation.py @@ -42,12 +42,6 @@ def test_bad_type_raises_exception(self): Neoantigen(patient_identifier="1234", rna_expression="0.45"), ) # this should be a float) - self.assertRaises( - NeofoxDataValidationException, - ModelValidator.validate, - Patient(identifier="1234", is_rna_available="Richtig"), - ) # this should be a boolean) - # TODO: make validation capture this data types errors! ModelValidator.validate( Neoantigen( @@ -63,7 +57,7 @@ def test_good_data_does_not_raise_exceptions(self): neoantigen = Neoantigen(patient_identifier="1234", rna_expression=0.45) ModelValidator.validate(neoantigen) - patient = Patient(identifier="1234", is_rna_available=True) + patient = Patient(identifier="1234") ModelValidator.validate(patient) def test_enum_with_wrong_value(self): @@ -695,20 +689,6 @@ def test_empty_patient_identifier(self): NeofoxDataValidationException, ModelValidator.validate_patient, patient, ORGANISM_HOMO_SAPIENS ) - def test_bad_is_rna_available(self): - ModelValidator.validate_patient( - Patient(identifier="123", is_rna_available=True), ORGANISM_HOMO_SAPIENS - ) - ModelValidator.validate_patient( - Patient(identifier="123", is_rna_available=False), ORGANISM_HOMO_SAPIENS - ) - self.assertRaises( - NeofoxDataValidationException, - ModelValidator.validate_patient, - Patient(identifier="123", is_rna_available="False"), - ORGANISM_HOMO_SAPIENS - ) - def test_validate_neoepitope_mhci(self): neoepitope = PredictedEpitope( mutated_peptide="DILVTDQTR", From fc99ba7ce47953464889e59c13b133467da79f8c Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Thu, 16 Mar 2023 10:44:24 +0100 Subject: [PATCH 11/83] make expression imputation more transparent and code in command file more clear --- neofox/__init__.py | 2 +- neofox/annotator/neoantigen_annotator.py | 1 + neofox/command_line.py | 9 ++-- neofox/neofox.py | 7 ++- neofox/published_features/expression.py | 24 ++++++++- neofox/published_features/priority_score.py | 52 ++++++++++++++++++- neofox/published_features/vaxrank/vaxrank.py | 19 ++++++- neofox/tests/integration_tests/test_neofox.py | 6 +-- neofox/tests/unit_tests/test_neofox.py | 4 +- .../tests/unit_tests/test_priority_score.py | 1 + 10 files changed, 110 insertions(+), 15 deletions(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index 1c226185..0557bdef 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b9" +VERSION = "1.1.0b10" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" diff --git a/neofox/annotator/neoantigen_annotator.py b/neofox/annotator/neoantigen_annotator.py index a6e5f1e2..812fd0ce 100755 --- a/neofox/annotator/neoantigen_annotator.py +++ b/neofox/annotator/neoantigen_annotator.py @@ -222,6 +222,7 @@ def get_annotated_neoantigen(self, neoantigen: Neoantigen, patient: Patient, wit neoantigen.neofox_annotations.annotations.extend(VaxRank().get_annotations( epitope_predictions=netmhcpan.predictions, expression_score=expression_annotation[0].value, + imputed_score=expression_annotation[1].value )) # hex diff --git a/neofox/command_line.py b/neofox/command_line.py index 204827e2..71e33e17 100755 --- a/neofox/command_line.py +++ b/neofox/command_line.py @@ -214,10 +214,11 @@ def _read_data(input_file, patients_data, mhc_database: MhcDatabase) -> Tuple[Li raise ValueError('Not supported input file extension: {}'.format(input_file)) ### Van -- check if patient candidates exist in the patient data file - neoantigens_patient_ids = set(i['patientIdentifier'] for i in neoantigens) - patient_ids = set(j['identifier'] for j in patients) - if neoantigens_patient_ids.difference(patient_ids) > 0: - raise ValueError('%s patient candidate does not exist in the patient data file.' % neoantigens_patient_ids) + neoantigens_patient_ids = set(neoantigen['patientIdentifier'] for neoantigen in neoantigens) + patient_ids = set(patient['identifier'] for patient in patients) + if len(neoantigens_patient_ids.difference(patient_ids)) > 0: + raise ValueError('%s patient candidate does not exist in the patient data file.' + % neoantigens_patient_ids.difference(patient_ids)) return neoantigens, patients diff --git a/neofox/neofox.py b/neofox/neofox.py index 40a698e2..535b12af 100755 --- a/neofox/neofox.py +++ b/neofox/neofox.py @@ -30,6 +30,7 @@ from neofox.model.factories import NeoantigenFactory from neofox.published_features.Tcell_predictor.tcellpredictor_wrapper import TcellPrediction from neofox.published_features.self_similarity.self_similarity import SelfSimilarityCalculator +from neofox.published_features.expression import Expression from neofox.references.references import ReferenceFolder, DependenciesConfiguration, ORGANISM_HOMO_SAPIENS from neofox import NEOFOX_LOG_FILE_ENV from neofox.annotator.neoantigen_annotator import NeoantigenAnnotator @@ -124,6 +125,7 @@ def __init__( def _conditional_expression_imputation(self) -> List[Neoantigen]: expression_annotator = ExpressionAnnotator() + expression = Expression() neoantigens_transformed = [] for neoantigen in self.neoantigens: @@ -133,10 +135,11 @@ def _conditional_expression_imputation(self) -> List[Neoantigen]: gene_expression = expression_annotator.get_gene_expression_annotation( gene_name=neoantigen.gene, tcga_cohort=patient.tumor_type ) - if expression_value is None and patient.tumor_type is not None and patient.tumor_type != "": - expression_value = gene_expression + #if expression_value is None and patient.tumor_type is not None and patient.tumor_type != "": + # expression_value = gene_expression neoantigen_transformed.rna_expression = expression_value neoantigen.imputed_gene_expression = gene_expression + neoantigens_transformed.append(neoantigen_transformed) return neoantigens_transformed diff --git a/neofox/published_features/expression.py b/neofox/published_features/expression.py index ce687805..da2ce78a 100755 --- a/neofox/published_features/expression.py +++ b/neofox/published_features/expression.py @@ -44,6 +44,22 @@ def _get_expression_annotation( pass return expression_mut + @staticmethod + def _get_geneExpression_annotation( + imputed_geneExpression: float, vaf_rna: float + ) -> float: + imputed_geneExpression_mut = None + try: + imputed_geneExpression_mut = ( + imputed_geneExpression * vaf_rna + if (vaf_rna is not None and vaf_rna >= 0.0) + #and (Patient.tumor_type is not None and Patient.tumor_type != "") + else None + ) + except(TypeError, ValueError): + pass + return imputed_geneExpression_mut + def get_annotations(self, neoantigen: Neoantigen) -> List[Annotation]: vaf = neoantigen.rna_variant_allele_frequency @@ -52,5 +68,9 @@ def get_annotations(self, neoantigen: Neoantigen) -> List[Annotation]: return [ AnnotationFactory.build_annotation( - name="Expression_mutated_transcript", value=self._get_expression_annotation( - transcript_expression=neoantigen.rna_expression, vaf_rna=vaf))] + name="Mutated_rnaExpression", value=self._get_expression_annotation( + transcript_expression=neoantigen.rna_expression, vaf_rna=vaf)), + AnnotationFactory.build_annotation( + name="Mutated_imputedGeneExpression", value=self._get_geneExpression_annotation( + imputed_geneExpression=neoantigen.imputed_gene_expression, vaf_rna=vaf)) + ] diff --git a/neofox/published_features/priority_score.py b/neofox/published_features/priority_score.py index 832b3354..fbe13c82 100755 --- a/neofox/published_features/priority_score.py +++ b/neofox/published_features/priority_score.py @@ -76,6 +76,41 @@ def calc_priority_score( pass return priority_score + def calc_priority_score_imputed( + self, + vaf_dna, + vaf_rna, + imputed_geneExpr, + no_mismatch, + score_mut, + score_wt, + mut_not_in_prot, + ): + """ + This function calculates the Priority Score using parameters for mhc I. + """ + priority_score_imputed = None + vaf = None + try: + if vaf_dna is not None and vaf_dna != -1: + vaf = vaf_dna + elif vaf_rna is not None and vaf_rna != -1: + vaf = vaf_rna + if vaf: + l_mut = self.calc_logistic_function(score_mut) + l_wt = self.calc_logistic_function(score_wt) + priority_score = self.mupexi( + l_mut=l_mut, + l_wt=l_wt, + mut_not_in_prot=mut_not_in_prot, + no_mismatch=no_mismatch, + imputed_geneExpr=imputed_geneExpr, + vaf_tumor=vaf + ) + except (TypeError, ValueError): + pass + return priority_score_imputed + def mupexi( self, l_mut, l_wt, mut_not_in_prot, no_mismatch, transcript_expr, vaf_tumor ): @@ -95,6 +130,7 @@ def get_annotations( """ num_mismatches_mhc1 = None priority_score = None + priority_score_imputed = None if netmhcpan.best_epitope_by_rank.wild_type_peptide and netmhcpan.best_epitope_by_rank.mutated_peptide: num_mismatches_mhc1 = EpitopeHelper.number_of_mismatches( epitope_wild_type=netmhcpan.best_epitope_by_rank.wild_type_peptide, @@ -113,6 +149,15 @@ def get_annotations( score_wt=netmhcpan.best_epitope_by_rank.rank_wild_type, mut_not_in_prot=mut_not_in_prot, ) + priority_score_imputed = self.calc_priority_score_imputed( + vaf_dna=neoantigen.dna_variant_allele_frequency, + vaf_rna=vaf_rna, + imputed_geneExpr=neoantigen.imputed_gene_expression, + no_mismatch=num_mismatches_mhc1, + score_mut=netmhcpan.best_epitope_by_rank.rank_mutated, + score_wt=netmhcpan.best_epitope_by_rank.rank_wild_type, + mut_not_in_prot=mut_not_in_prot, + ) annotations = [ AnnotationFactory.build_annotation( value=num_mismatches_mhc1, name="Number_of_mismatches_MCHI" @@ -122,6 +167,11 @@ def get_annotations( value=priority_score, name="Priority_score", ), + # imputed priority score with rank score + AnnotationFactory.build_annotation( + value=priority_score_imputed, + name="Priority_score_imputed" + ) ] return annotations @@ -139,5 +189,5 @@ def get_annotations_epitope_mhci(self, epitope: PredictedEpitope, vaf_tumor, tra score_wt=epitope.rank_wild_type, mut_not_in_prot=bool(EpitopeHelper.get_annotation_by_name( epitope.neofox_annotations.annotations, name='mutation_not_found_in_proteome'))), - name='Priority_score') + name='Priority_score'), ] diff --git a/neofox/published_features/vaxrank/vaxrank.py b/neofox/published_features/vaxrank/vaxrank.py index 21d317e4..a8472fa7 100755 --- a/neofox/published_features/vaxrank/vaxrank.py +++ b/neofox/published_features/vaxrank/vaxrank.py @@ -82,10 +82,24 @@ def combined_score(self, expression_score, total_binding_score): pass return combined_score - def get_annotations(self, epitope_predictions: List[PredictedEpitope], expression_score) -> List[Annotation]: + def combined_score_imputed (self, imputed_score, total_binding_score): + """ + adapted from: https://github.com/openvax/vaxrank/blob/master/vaxrank/epitope_prediction.py + final ranking score implemented in VaxRank + """ + combined_score_imputed = None + try: + combined_score_imputed = float(imputed_score) * total_binding_score + except (ValueError, TypeError): + pass + return combined_score_imputed + + def get_annotations(self, epitope_predictions: List[PredictedEpitope], expression_score, imputed_score) -> List[Annotation]: expression_score = expression_score + imputed_score = imputed_score total_binding_score = self.total_binding(epitope_predictions) ranking_score = self.combined_score(expression_score=expression_score, total_binding_score=total_binding_score) + ranking_score_imputed = self.combined_score_imputed(imputed_score=imputed_score, total_binding_score=total_binding_score) return [ AnnotationFactory.build_annotation( value=total_binding_score, name="Vaxrank_bindingScore" @@ -93,4 +107,7 @@ def get_annotations(self, epitope_predictions: List[PredictedEpitope], expressio AnnotationFactory.build_annotation( value=ranking_score, name="Vaxrank_totalScore" ), + AnnotationFactory.build_annotation( + value=ranking_score_imputed, name="Vaxrank_totalScore_imputed" + ) ] diff --git a/neofox/tests/integration_tests/test_neofox.py b/neofox/tests/integration_tests/test_neofox.py index 4d885ec4..83ac3088 100755 --- a/neofox/tests/integration_tests/test_neofox.py +++ b/neofox/tests/integration_tests/test_neofox.py @@ -204,7 +204,7 @@ def test_neofox_model_input(self): ).get_annotations() self.assertEqual(5, len(annotations)) self.assertIsInstance(annotations[0], Neoantigen) - self.assertTrue(len(annotations[0].neofox_annotations.annotations) == 82) + self.assertTrue(len(annotations[0].neofox_annotations.annotations) ==85) def test_neofox_without_mixmhcpreds(self): """ @@ -328,7 +328,7 @@ def test_neofox_without_mhc2(self): ).get_annotations() self.assertEqual(5, len(annotations)) self.assertIsInstance(annotations[0], Neoantigen) - self.assertEqual(len(annotations[0].neofox_annotations.annotations), 63) + self.assertEqual(len(annotations[0].neofox_annotations.annotations), 66) def test_neofox_without_mhc1(self): neoantigens, patients = self._get_test_data() @@ -341,7 +341,7 @@ def test_neofox_without_mhc1(self): ).get_annotations() self.assertEqual(5, len(annotations)) self.assertIsInstance(annotations[0], Neoantigen) - self.assertEqual(len(annotations[0].neofox_annotations.annotations), 39) + self.assertEqual(len(annotations[0].neofox_annotations.annotations), 40) def test_gene_expression_imputation(self): neoantigens, patients = self._get_test_data() diff --git a/neofox/tests/unit_tests/test_neofox.py b/neofox/tests/unit_tests/test_neofox.py index f93f5d84..83eccc07 100755 --- a/neofox/tests/unit_tests/test_neofox.py +++ b/neofox/tests/unit_tests/test_neofox.py @@ -194,7 +194,9 @@ def test_with_expression_imputation(self): for neoantigen, neoantigen_imputed in zip(original_neoantigens, neofox_runner.neoantigens): self.assertIsNotNone(neoantigen_imputed.imputed_gene_expression) if neoantigen.rna_expression is None: - self.assertNotEqual(neoantigen.rna_expression, neoantigen_imputed.rna_expression) + #self.assertNotEqual(neoantigen.rna_expression, neoantigen_imputed.rna_expression) + self.assertTrue(neoantigen.rna_expression==neoantigen_imputed.rna_expression or + (neoantigen.rna_expression is None and neoantigen_imputed.rna_expression is None)) else: self.assertEqual(neoantigen.rna_expression, neoantigen_imputed.rna_expression) diff --git a/neofox/tests/unit_tests/test_priority_score.py b/neofox/tests/unit_tests/test_priority_score.py index c6803443..3a0bc088 100755 --- a/neofox/tests/unit_tests/test_priority_score.py +++ b/neofox/tests/unit_tests/test_priority_score.py @@ -35,6 +35,7 @@ def test_priority(self): mut_not_in_prot=True, ) self.assertGreater(result, 0) + result = self.priority_calculator.calc_priority_score( vaf_dna=None, vaf_rna=0.33, From 6c94b147035b286c8ddfa2386abd9714d74b775c Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Thu, 23 Mar 2023 12:41:27 +0100 Subject: [PATCH 12/83] update calculations of features expressions and shorten unneeded code in neofox.py --- docs/source/03_02_output_data.md | 183 +++++++++--------- neofox/command_line.py | 5 +- neofox/neofox.py | 4 +- neofox/published_features/priority_score.py | 51 +---- neofox/published_features/vaxrank/vaxrank.py | 22 +-- .../tests/unit_tests/test_priority_score.py | 12 +- 6 files changed, 114 insertions(+), 163 deletions(-) diff --git a/docs/source/03_02_output_data.md b/docs/source/03_02_output_data.md index 7e1abbff..e97db3b6 100755 --- a/docs/source/03_02_output_data.md +++ b/docs/source/03_02_output_data.md @@ -12,96 +12,99 @@ The following table describes each of the annotations in the output: **TABLE 1** -| Column name | Description | Feature group/ Paper | -|---------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------| -| dnaVariantAlleleFrequency | the variant allele frequency calculated from the DNA | - | -| mutatedXmer | the long mutated amino acid sequence | - | -| wildTypeXmer | the long non-mutated amino acid sequence. This field shall be empty for alternative neoantigen classes | - | -| patientIdentifier | the patient identifier | - | -| rnaExpression | the RNA expression. If expression was imputed, this will will be `imputedGeneExpression` | expression | -| imputedGeneExpression | median gene expression in the TCGA cohort of the tumor entity provided in the patient file. | expression | -| rnaVariantAlleleFrequency | the variant allele frequency calculated from the RNA | - | -| gene | the HGNC gene symbol | - | -| Expression_mutated_transcript | transcript expression normalized by the variant allele frequency of the mutation | expression | -| mutation_not_found_in_proteome | indicates if mutated amino acid sequence was not found in the WT proteome by exact search | Priority score | -| NetMHCpan_bestRank_rank | minimal MHC I binding rank score over all neoepitope candidates (8-11mers) and MHC I alleles | MHC I binding with netMHCpan | -| NetMHCpan_bestRank_peptide | neoepitope candidate sequence with minimal MHC I binding rank score | MHC I binding with netMHCpan | -| NetMHCpan_bestRank_allele | the MHC I allele related to `NetMHCpan_bestRank_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity_affinity | minimal MHC I binding affinity over all neoepitope candidates (8-11mers) and MHC I alleles | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity_peptide | neoepitope candidate sequence with minimal MHC I binding affinity | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity_allele | the MHC I allele related to `NetMHCpan_bestAffinity_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestRank9mer_rank | minimal MHC I binding rank score over all neoepitope candidates (9mers only) and MHC I alleles | MHC I binding with netMHCpan | -| NetMHCpan_bestRank9mer_peptide | neoepitope candidate sequence (9mer) with minimal MHC I binding rank score | MHC I binding with netMHCpan | -| NetMHCpan_bestRank9mer_allele | the MHC I allele related to `NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_affinity | minimal MHC I binding affinity over all neoepitope candidates (9mers) and MHC I alleles | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_allele | the MHC I allele related to `NetMHCpan_bestAffinity9mer_peptide ` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_peptide | neoepitope candidate sequence (9mer) with minimal MHC I binding affinity | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity_affinityWT | MHC I binding affinity of `NetMHCpan_bestAffinity_peptideWT` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity_peptideWT | WT epitope that corresponds to `NetMHCpan_bestAffinity_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestRank_rankWT | MHC I binding rank score of `NetMHCpan_bestRank_peptideWT` | MHC I binding with netMHCpan | -| NetMHCpan_bestRank_peptideWT | WT epitope that corresponds to `NetMHCpan_bestRank_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestRank9mer_rankWT | MHC I binding rank score of `NetMHCpan_bestRank9mer_peptideWT ` | MHC I binding with netMHCpan | -| NetMHCpan_bestRank9mer_peptideWT | WT epitope that corresponds to `NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_affinityWT | MHC I binding affinity of ` NetMHCpan_bestAffinity9mer_peptideWT ` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_peptideWT | WT epitope that corresponds to `NetMHCpan_bestAffinity9mer_peptide` | | -| PHBR_I | harmonic mean of minimal MHC I binding rank scores of all MHC I alleles of a patient | PHBR-I | -| NetMHCpan_bestAffinity9mer_positionMutation | indicates position of the mutation in ` NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | -| NetMHCpan_bestAffinity9mer_anchorMutated | mutation in `NetMHCpan_bestRank9mer_peptide` in an anchor position (i.e. position 2 or 9) | anchor/non-anchor | -| NetMHCIIpan_bestRank_rank | minimal MHC II binding rank score over all neoepitope candidates (15mers) and all MHC II alleles | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestRank_peptide | neoepitope candidate sequence with minimal MHC II binding rank score | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestRank_allele | the MHC II isoform related to `NetMHCIIpan_bestRank_peptide` | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestAffinity_affinity | minimal MHC II binding affinity over all neoepitope candidates (15mers) and all MHC II alleles | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestAffinity_peptide | neoepitope candidate sequence with minimal MHC II binding affinity | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestAffinity_allele | the MHC II isoform related to `NetMHCIIpan_bestAffinity_peptide` | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestRank_rankWT | minimal MHC II binding rank of `NetMHCIIpan_bestRank_peptideWT` | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestRank_peptideWT | WT epitope sequence (15mer) that corresponds to ` NetMHCIIpan_bestRank_peptide` | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestAffinity_affinityWT | minimal MHC II binding rank of `NetMHCIIpan_bestAffinity_peptideWT` | MHC II binding with netMHCIIpan | -| NetMHCIIpan_bestAffinity_peptideWT | WT epitope sequence (15mer) that corresponds to `NetMHCIIpan_bestAffinity_peptide` | MHC II binding with netMHCIIpan | -| PHBR_II | harmonic mean of minimal MHC II binding rank scores of all MHC II alleles of a patient | PHBR-II | -| Amplitude_MHCI_bestAffinity9mer | ratio of `NetMHCpan_bestAffinity9mer_affinity` and `NetMHCpan_bestAffinity9mer_affinityWT` | Recognition Potential | -| Amplitude_MHCI_bestAffinity | ratio of `NetMHCpan_bestAffinity_affinityWT` and `NetMHCpan_bestAffinity_affinity` | Generator rate | -| Amplitude_MHCII_bestRank | ratio of `NetMHCIIpan_bestRank_rank` and `NetMHCIIpan_bestRank_rankWT` | Generator rate | -| Pathogensimiliarity_MHCI_bestAffinity9mer | score representing the similarity of `NetMHCpan_bestAffinity9mer_peptide` to pathogen sequences in IEDB database | Recognition Potential | -| Pathogensimiliarity_MHCII_bestAffinity | score representing the similarity of `NetMHCIIpan_bestRank_peptide` to pathogen sequences in IEDB database | Recognition Potential | -| RecognitionPotential_MHCI_bestAffinity9mer | product of `Amplitude_MHCI_affinity_9mer` and `Pathogensimiliarity_MHCI_affinity_9mer` | Recognition Potential | -| DAI_MHCI_bestAffinity | difference of `NetMHCpan_bestAffinity_affinityWT` and `NetMHCpan_bestAffinity_affinity` | DAI | -| Classically_defined_neopeptide_MHCI | `NetMHCpan_bestAffinity_peptide`< 50 nM | Generator rate | -| Alternatively_defined_neopeptide_MHCI | `NetMHCpan_bestAffinity_peptide` < 5000 nM and `Amplitude_MHCI_bestAffinity` > 10 | Generator rate | -| Classically_defined_neopeptide_MHCII | `NetMHCIIpan_bestRank_rank` < 1 | Generator rate | -| Alternatively_defined_neopeptide_MHCII | `Best_rank_MHCII_score` < 4 and `Amplitude_MHCII_bestRank` < 2 | Generator rate | -| GeneratorRate_CDN_MHCI | number of neoepitope candidates with MHC I binding affinity < 50 nM per neoantigen canidate | Generator rate | -| GeneratorRate_ADN_MHCI | number of neoepitope candidates with MHC I binding affinity < 5000 nM per neoantigen canidate 10x better affinity in comparison to corresponding WT peptide | Generator rate | -| GeneratorRate_MHCI | sum of `GeneratorRate_CDN_MHCI` and `GeneratorRate_ADN_MHCI` | Generator rate | -| GeneratorRate_CDN_MHCII | number of neoepitope candidates with MHC II binding rank score < 1 per neoantigen canidate | Generator rate | -| GeneratorRate_ADN_MHCII | number of neoepitope candidates with MHC II binding rank score < 4 per neoantigen candidate 4x better rank in comparison to corresponding WT peptide | Generator rate | -| GeneratorRate_MHCII | sum of `GeneratorRate_CDN_MHCII` and `GeneratorRate_ADN_MHCII` | Generator rate | -| Tcell_predictor | output score of T cell predictor model | Tcell predictor | -| ImprovedBinder_MHCI | ratio of `NetMHCpan_MHCI_rank_bestRankWT` and `NetMHCpan_MHCI_rank_bestRank` > 1.2 | self-similarity | -| Selfsimilarity_MHCI_conserved_binder | score representing the similarity between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptideWT` For conservered binder only | self-similarity | -| Selfsimilarity_MHCI | score representing the similarity between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptide` | self-similarity | -| Selfsimilarity_MHCII | score representing the similarity between `NetMHCIIpan_bestAffinity_peptide` and `NetMHCIIpan_bestAffinity_peptide` | self-similarity | -| Number_of_mismatches_MCHI | number of amino acids that do no match between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptideWT` | Priority score | -| Priority_score | combinatorial score of several features such as MHC binding, expression and VAF | Priority score | -| Neoag_immunogenicity | output score of neoag model | neoag | -| IEDB_Immunogenicity_MHCI | IEDB Immunogenicity score for `NetMHCpan_bestAffinity_peptide` | IEDB Immunogenicity | -| IEDB_Immunogenicity_MHCII | IEDB Immunogenicity score for `NetMHCIIpan_bestAffinity_peptide` | IEDB Immunogenicity | -| MixMHCpred_bestScore_peptide | MHC class I neoepitope candidate sequence with maximum MixMHCpred score over all neoepitope canidates (8-11mers) and MHC I alleles | MixMHCpred | -| MixMHCpred_bestScore_score | maximum MixMHCpred score over all neoepitope canidates (8-11mers) and MHC I alleles | MixMHCpred | -| MixMHCpred_bestScore_rank | rank that corresponds to `MixMHCpred_bestScore_score` | MixMHCpred | -| MixMHCpred_bestScore_allele | the allele with maximum MixMHCpred score | MixMHCpred | -| MixMHC2pred_bestRank_peptide | MHC class II neoepitope candidate sequence with minimal MixMHC2pred score over all neoepitope canidates (13-18mers) and MHC II alleles | MixMHC2pred | -| MixMHC2pred_bestRank_rank | minimal MixMHC2pred score over all neoepitope canidates (13-18mers) and MHC II alleles | MixMHC2pred | -| MixMHC2pred_bestRank_allele | the MHC II isoform with minimum MixMHC2pred rank score | MixMHC2pred | -| Dissimilarity_MHCI | score reflecting the dissimilarity of `NetMHCpan_bestAffinity_peptide` to the self-proteome | dissimilarity | -| Dissimilarity_MHCII | score reflecting the dissimilarity of `NetMHCIIpan_bestAffinity_peptide` to the self-proteome | dissimilarity | -| Vaxrank_bindingScore | total binding score of vaxrank | vaxrank | -| Vaxrank_totalScore | product of total binding score and expression score. Originally, the root of the number of reads supporting the mutation are used in the original implementation. To simplify, the expression normalised to VAF is used. | vaxrank | -| PRIME_bestScore_allele | best predicted MHC allele by PRIME model | PRIME | -| PRIME_bestScore_peptide | best predicted neoepitope candidate by PRIME model | PRIME | -| PRIME_bestScore_rank | output rank score of PRIME model | PRIME | -| PRIME_bestScore_score | output score of PRIME model | PRIME | -| HexAlignmentScore_MHCI | the alignment score by HEX for `NetMHCpan_bestAffinity_peptide` | HEX | -| HexAlignmentScore_MHCII | the alignment score by HEX for `NetMHCIIpan_bestAffinity_peptide` | HEX | +| Column name | Description | Feature group/ Paper | +|---------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------| +| dnaVariantAlleleFrequency | the variant allele frequency calculated from the DNA | - | +| mutatedXmer | the long mutated amino acid sequence | - | +| wildTypeXmer | the long non-mutated amino acid sequence. This field shall be empty for alternative neoantigen classes | - | +| patientIdentifier | the patient identifier | - | +| rnaExpression | the RNA expression. If expression was imputed, this will will be `imputedGeneExpression` | expression | +| imputedGeneExpression | median gene expression in the TCGA cohort of the tumor entity provided in the patient file. | expression | +| rnaVariantAlleleFrequency | the variant allele frequency calculated from the RNA | - | +| gene | the HGNC gene symbol | - | +| Mutated_rnaExpression | transcript expression normalized by the variant allele frequency of the mutation | expression | +| Mutated_imputedGeneExpression | imputed gene expression normalized by the variant allele frequency of the mutation | | +| mutation_not_found_in_proteome | indicates if mutated amino acid sequence was not found in the WT proteome by exact search | Priority score | +| NetMHCpan_bestRank_rank | minimal MHC I binding rank score over all neoepitope candidates (8-11mers) and MHC I alleles | MHC I binding with netMHCpan | +| NetMHCpan_bestRank_peptide | neoepitope candidate sequence with minimal MHC I binding rank score | MHC I binding with netMHCpan | +| NetMHCpan_bestRank_allele | the MHC I allele related to `NetMHCpan_bestRank_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_affinity | minimal MHC I binding affinity over all neoepitope candidates (8-11mers) and MHC I alleles | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_peptide | neoepitope candidate sequence with minimal MHC I binding affinity | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_allele | the MHC I allele related to `NetMHCpan_bestAffinity_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestRank9mer_rank | minimal MHC I binding rank score over all neoepitope candidates (9mers only) and MHC I alleles | MHC I binding with netMHCpan | +| NetMHCpan_bestRank9mer_peptide | neoepitope candidate sequence (9mer) with minimal MHC I binding rank score | MHC I binding with netMHCpan | +| NetMHCpan_bestRank9mer_allele | the MHC I allele related to `NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_affinity | minimal MHC I binding affinity over all neoepitope candidates (9mers) and MHC I alleles | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_allele | the MHC I allele related to `NetMHCpan_bestAffinity9mer_peptide ` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_peptide | neoepitope candidate sequence (9mer) with minimal MHC I binding affinity | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_affinityWT | MHC I binding affinity of `NetMHCpan_bestAffinity_peptideWT` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_peptideWT | WT epitope that corresponds to `NetMHCpan_bestAffinity_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestRank_rankWT | MHC I binding rank score of `NetMHCpan_bestRank_peptideWT` | MHC I binding with netMHCpan | +| NetMHCpan_bestRank_peptideWT | WT epitope that corresponds to `NetMHCpan_bestRank_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestRank9mer_rankWT | MHC I binding rank score of `NetMHCpan_bestRank9mer_peptideWT ` | MHC I binding with netMHCpan | +| NetMHCpan_bestRank9mer_peptideWT | WT epitope that corresponds to `NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_affinityWT | MHC I binding affinity of ` NetMHCpan_bestAffinity9mer_peptideWT ` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_peptideWT | WT epitope that corresponds to `NetMHCpan_bestAffinity9mer_peptide` | | +| PHBR_I | harmonic mean of minimal MHC I binding rank scores of all MHC I alleles of a patient | PHBR-I | +| NetMHCpan_bestAffinity9mer_positionMutation | indicates position of the mutation in ` NetMHCpan_bestRank9mer_peptide` | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity9mer_anchorMutated | mutation in `NetMHCpan_bestRank9mer_peptide` in an anchor position (i.e. position 2 or 9) | anchor/non-anchor | +| NetMHCIIpan_bestRank_rank | minimal MHC II binding rank score over all neoepitope candidates (15mers) and all MHC II alleles | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestRank_peptide | neoepitope candidate sequence with minimal MHC II binding rank score | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestRank_allele | the MHC II isoform related to `NetMHCIIpan_bestRank_peptide` | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestAffinity_affinity | minimal MHC II binding affinity over all neoepitope candidates (15mers) and all MHC II alleles | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestAffinity_peptide | neoepitope candidate sequence with minimal MHC II binding affinity | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestAffinity_allele | the MHC II isoform related to `NetMHCIIpan_bestAffinity_peptide` | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestRank_rankWT | minimal MHC II binding rank of `NetMHCIIpan_bestRank_peptideWT` | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestRank_peptideWT | WT epitope sequence (15mer) that corresponds to ` NetMHCIIpan_bestRank_peptide` | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestAffinity_affinityWT | minimal MHC II binding rank of `NetMHCIIpan_bestAffinity_peptideWT` | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestAffinity_peptideWT | WT epitope sequence (15mer) that corresponds to `NetMHCIIpan_bestAffinity_peptide` | MHC II binding with netMHCIIpan | +| PHBR_II | harmonic mean of minimal MHC II binding rank scores of all MHC II alleles of a patient | PHBR-II | +| Amplitude_MHCI_bestAffinity9mer | ratio of `NetMHCpan_bestAffinity9mer_affinity` and `NetMHCpan_bestAffinity9mer_affinityWT` | Recognition Potential | +| Amplitude_MHCI_bestAffinity | ratio of `NetMHCpan_bestAffinity_affinityWT` and `NetMHCpan_bestAffinity_affinity` | Generator rate | +| Amplitude_MHCII_bestRank | ratio of `NetMHCIIpan_bestRank_rank` and `NetMHCIIpan_bestRank_rankWT` | Generator rate | +| Pathogensimiliarity_MHCI_bestAffinity9mer | score representing the similarity of `NetMHCpan_bestAffinity9mer_peptide` to pathogen sequences in IEDB database | Recognition Potential | +| Pathogensimiliarity_MHCII_bestAffinity | score representing the similarity of `NetMHCIIpan_bestRank_peptide` to pathogen sequences in IEDB database | Recognition Potential | +| RecognitionPotential_MHCI_bestAffinity9mer | product of `Amplitude_MHCI_affinity_9mer` and `Pathogensimiliarity_MHCI_affinity_9mer` | Recognition Potential | +| DAI_MHCI_bestAffinity | difference of `NetMHCpan_bestAffinity_affinityWT` and `NetMHCpan_bestAffinity_affinity` | DAI | +| Classically_defined_neopeptide_MHCI | `NetMHCpan_bestAffinity_peptide`< 50 nM | Generator rate | +| Alternatively_defined_neopeptide_MHCI | `NetMHCpan_bestAffinity_peptide` < 5000 nM and `Amplitude_MHCI_bestAffinity` > 10 | Generator rate | +| Classically_defined_neopeptide_MHCII | `NetMHCIIpan_bestRank_rank` < 1 | Generator rate | +| Alternatively_defined_neopeptide_MHCII | `Best_rank_MHCII_score` < 4 and `Amplitude_MHCII_bestRank` < 2 | Generator rate | +| GeneratorRate_CDN_MHCI | number of neoepitope candidates with MHC I binding affinity < 50 nM per neoantigen canidate | Generator rate | +| GeneratorRate_ADN_MHCI | number of neoepitope candidates with MHC I binding affinity < 5000 nM per neoantigen canidate 10x better affinity in comparison to corresponding WT peptide | Generator rate | +| GeneratorRate_MHCI | sum of `GeneratorRate_CDN_MHCI` and `GeneratorRate_ADN_MHCI` | Generator rate | +| GeneratorRate_CDN_MHCII | number of neoepitope candidates with MHC II binding rank score < 1 per neoantigen canidate | Generator rate | +| GeneratorRate_ADN_MHCII | number of neoepitope candidates with MHC II binding rank score < 4 per neoantigen candidate 4x better rank in comparison to corresponding WT peptide | Generator rate | +| GeneratorRate_MHCII | sum of `GeneratorRate_CDN_MHCII` and `GeneratorRate_ADN_MHCII` | Generator rate | +| Tcell_predictor | output score of T cell predictor model | Tcell predictor | +| ImprovedBinder_MHCI | ratio of `NetMHCpan_MHCI_rank_bestRankWT` and `NetMHCpan_MHCI_rank_bestRank` > 1.2 | self-similarity | +| Selfsimilarity_MHCI_conserved_binder | score representing the similarity between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptideWT` For conservered binder only | self-similarity | +| Selfsimilarity_MHCI | score representing the similarity between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptide` | self-similarity | +| Selfsimilarity_MHCII | score representing the similarity between `NetMHCIIpan_bestAffinity_peptide` and `NetMHCIIpan_bestAffinity_peptide` | self-similarity | +| Number_of_mismatches_MCHI | number of amino acids that do no match between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptideWT` | Priority score | +| Priority_score | combinatorial score of several features such as MHC binding, transcription expression and VAF | Priority score | +| Priority_score_imputed | combinatorial score of several features such as MHC binding, imputed gene expression and VAF | Priority score | +| Neoag_immunogenicity | output score of neoag model | neoag | +| IEDB_Immunogenicity_MHCI | IEDB Immunogenicity score for `NetMHCpan_bestAffinity_peptide` | IEDB Immunogenicity | +| IEDB_Immunogenicity_MHCII | IEDB Immunogenicity score for `NetMHCIIpan_bestAffinity_peptide` | IEDB Immunogenicity | +| MixMHCpred_bestScore_peptide | MHC class I neoepitope candidate sequence with maximum MixMHCpred score over all neoepitope canidates (8-11mers) and MHC I alleles | MixMHCpred | +| MixMHCpred_bestScore_score | maximum MixMHCpred score over all neoepitope canidates (8-11mers) and MHC I alleles | MixMHCpred | +| MixMHCpred_bestScore_rank | rank that corresponds to `MixMHCpred_bestScore_score` | MixMHCpred | +| MixMHCpred_bestScore_allele | the allele with maximum MixMHCpred score | MixMHCpred | +| MixMHC2pred_bestRank_peptide | MHC class II neoepitope candidate sequence with minimal MixMHC2pred score over all neoepitope canidates (13-18mers) and MHC II alleles | MixMHC2pred | +| MixMHC2pred_bestRank_rank | minimal MixMHC2pred score over all neoepitope canidates (13-18mers) and MHC II alleles | MixMHC2pred | +| MixMHC2pred_bestRank_allele | the MHC II isoform with minimum MixMHC2pred rank score | MixMHC2pred | +| Dissimilarity_MHCI | score reflecting the dissimilarity of `NetMHCpan_bestAffinity_peptide` to the self-proteome | dissimilarity | +| Dissimilarity_MHCII | score reflecting the dissimilarity of `NetMHCIIpan_bestAffinity_peptide` to the self-proteome | dissimilarity | +| Vaxrank_bindingScore | total binding score of vaxrank | vaxrank | +| Vaxrank_totalScore | product of total binding score and transcription expression score. Originally, the root of the number of reads supporting the mutation are used in the original implementation. To simplify, the expression normalised to VAF is used. | vaxrank | +| Vaxrank_totalScore_imputed | product of total binding score and imputed gene expression score. Originally, the root of the number of reads supporting the mutation are used in the original implementation. To simplify, the expression normalised to VAF is used. | vaxrank | +| PRIME_bestScore_allele | best predicted MHC allele by PRIME model | PRIME | +| PRIME_bestScore_peptide | best predicted neoepitope candidate by PRIME model | PRIME | +| PRIME_bestScore_rank | output rank score of PRIME model | PRIME | +| PRIME_bestScore_score | output score of PRIME model | PRIME | +| HexAlignmentScore_MHCI | the alignment score by HEX for `NetMHCpan_bestAffinity_peptide` | HEX | +| HexAlignmentScore_MHCII | the alignment score by HEX for `NetMHCIIpan_bestAffinity_peptide` | HEX | In addition, all logging output is appended to a log file with the suffix diff --git a/neofox/command_line.py b/neofox/command_line.py index 71e33e17..ecbc3d5e 100755 --- a/neofox/command_line.py +++ b/neofox/command_line.py @@ -213,9 +213,8 @@ def _read_data(input_file, patients_data, mhc_database: MhcDatabase) -> Tuple[Li else: raise ValueError('Not supported input file extension: {}'.format(input_file)) - ### Van -- check if patient candidates exist in the patient data file - neoantigens_patient_ids = set(neoantigen['patientIdentifier'] for neoantigen in neoantigens) - patient_ids = set(patient['identifier'] for patient in patients) + neoantigens_patient_ids = set(neoantigen.patient_identifier for neoantigen in neoantigens) + patient_ids = set(patient.identifier for patient in patients) if len(neoantigens_patient_ids.difference(patient_ids)) > 0: raise ValueError('%s patient candidate does not exist in the patient data file.' % neoantigens_patient_ids.difference(patient_ids)) diff --git a/neofox/neofox.py b/neofox/neofox.py index 535b12af..7fb7e614 100755 --- a/neofox/neofox.py +++ b/neofox/neofox.py @@ -125,7 +125,6 @@ def __init__( def _conditional_expression_imputation(self) -> List[Neoantigen]: expression_annotator = ExpressionAnnotator() - expression = Expression() neoantigens_transformed = [] for neoantigen in self.neoantigens: @@ -135,8 +134,7 @@ def _conditional_expression_imputation(self) -> List[Neoantigen]: gene_expression = expression_annotator.get_gene_expression_annotation( gene_name=neoantigen.gene, tcga_cohort=patient.tumor_type ) - #if expression_value is None and patient.tumor_type is not None and patient.tumor_type != "": - # expression_value = gene_expression + neoantigen_transformed.rna_expression = expression_value neoantigen.imputed_gene_expression = gene_expression diff --git a/neofox/published_features/priority_score.py b/neofox/published_features/priority_score.py index fbe13c82..4e5e8897 100755 --- a/neofox/published_features/priority_score.py +++ b/neofox/published_features/priority_score.py @@ -45,7 +45,7 @@ def calc_priority_score( self, vaf_dna, vaf_rna, - transcript_expr, + transcript_gene_expr, no_mismatch, score_mut, score_wt, @@ -69,52 +69,17 @@ def calc_priority_score( l_wt=l_wt, mut_not_in_prot=mut_not_in_prot, no_mismatch=no_mismatch, - transcript_expr=transcript_expr, + transcript_gene_expr=transcript_gene_expr, vaf_tumor=vaf ) except (TypeError, ValueError): pass return priority_score - def calc_priority_score_imputed( - self, - vaf_dna, - vaf_rna, - imputed_geneExpr, - no_mismatch, - score_mut, - score_wt, - mut_not_in_prot, - ): - """ - This function calculates the Priority Score using parameters for mhc I. - """ - priority_score_imputed = None - vaf = None - try: - if vaf_dna is not None and vaf_dna != -1: - vaf = vaf_dna - elif vaf_rna is not None and vaf_rna != -1: - vaf = vaf_rna - if vaf: - l_mut = self.calc_logistic_function(score_mut) - l_wt = self.calc_logistic_function(score_wt) - priority_score = self.mupexi( - l_mut=l_mut, - l_wt=l_wt, - mut_not_in_prot=mut_not_in_prot, - no_mismatch=no_mismatch, - imputed_geneExpr=imputed_geneExpr, - vaf_tumor=vaf - ) - except (TypeError, ValueError): - pass - return priority_score_imputed - def mupexi( - self, l_mut, l_wt, mut_not_in_prot, no_mismatch, transcript_expr, vaf_tumor + self, l_mut, l_wt, mut_not_in_prot, no_mismatch, transcript_gene_expr, vaf_tumor ): - priority_score = (l_mut * vaf_tumor * math.tanh(transcript_expr)) * ( + priority_score = (l_mut * vaf_tumor * math.tanh(transcript_gene_expr)) * ( float(mut_not_in_prot) * (1 - 2 ** (-no_mismatch) * l_wt) ) return priority_score @@ -143,16 +108,16 @@ def get_annotations( priority_score = self.calc_priority_score( vaf_dna=neoantigen.dna_variant_allele_frequency, vaf_rna=vaf_rna, - transcript_expr=neoantigen.rna_expression, + transcript_gene_expr=neoantigen.rna_expression, no_mismatch=num_mismatches_mhc1, score_mut=netmhcpan.best_epitope_by_rank.rank_mutated, score_wt=netmhcpan.best_epitope_by_rank.rank_wild_type, mut_not_in_prot=mut_not_in_prot, ) - priority_score_imputed = self.calc_priority_score_imputed( + priority_score_imputed = self.calc_priority_score( vaf_dna=neoantigen.dna_variant_allele_frequency, vaf_rna=vaf_rna, - imputed_geneExpr=neoantigen.imputed_gene_expression, + transcript_gene_expr=neoantigen.imputed_gene_expression, no_mismatch=num_mismatches_mhc1, score_mut=netmhcpan.best_epitope_by_rank.rank_mutated, score_wt=netmhcpan.best_epitope_by_rank.rank_wild_type, @@ -182,7 +147,7 @@ def get_annotations_epitope_mhci(self, epitope: PredictedEpitope, vaf_tumor, tra value=self.calc_priority_score( vaf_dna=vaf_tumor, vaf_rna=vaf_rna, - transcript_expr=transcript_exp, + transcript_gene_expr=transcript_exp, no_mismatch=int(EpitopeHelper.get_annotation_by_name( epitope.neofox_annotations.annotations, name='number_of_mismatches')), score_mut=epitope.rank_mutated, diff --git a/neofox/published_features/vaxrank/vaxrank.py b/neofox/published_features/vaxrank/vaxrank.py index a8472fa7..30efb399 100755 --- a/neofox/published_features/vaxrank/vaxrank.py +++ b/neofox/published_features/vaxrank/vaxrank.py @@ -70,36 +70,22 @@ def total_binding(self, epitope_predictions: List[PredictedEpitope]): return mut_scores_logistic - def combined_score(self, expression_score, total_binding_score): + def combined_score(self, expression_imputed_score, total_binding_score): """ adapted from: https://github.com/openvax/vaxrank/blob/master/vaxrank/epitope_prediction.py final ranking score implemented in VaxRank """ combined_score = None try: - combined_score = float(expression_score) * total_binding_score + combined_score = float(expression_imputed_score) * total_binding_score except (ValueError, TypeError): pass return combined_score - def combined_score_imputed (self, imputed_score, total_binding_score): - """ - adapted from: https://github.com/openvax/vaxrank/blob/master/vaxrank/epitope_prediction.py - final ranking score implemented in VaxRank - """ - combined_score_imputed = None - try: - combined_score_imputed = float(imputed_score) * total_binding_score - except (ValueError, TypeError): - pass - return combined_score_imputed - def get_annotations(self, epitope_predictions: List[PredictedEpitope], expression_score, imputed_score) -> List[Annotation]: - expression_score = expression_score - imputed_score = imputed_score total_binding_score = self.total_binding(epitope_predictions) - ranking_score = self.combined_score(expression_score=expression_score, total_binding_score=total_binding_score) - ranking_score_imputed = self.combined_score_imputed(imputed_score=imputed_score, total_binding_score=total_binding_score) + ranking_score = self.combined_score(expression_imputed_score=expression_score, total_binding_score=total_binding_score) + ranking_score_imputed = self.combined_score(expression_imputed_score=imputed_score, total_binding_score=total_binding_score) return [ AnnotationFactory.build_annotation( value=total_binding_score, name="Vaxrank_bindingScore" diff --git a/neofox/tests/unit_tests/test_priority_score.py b/neofox/tests/unit_tests/test_priority_score.py index 3a0bc088..a9e87dbc 100755 --- a/neofox/tests/unit_tests/test_priority_score.py +++ b/neofox/tests/unit_tests/test_priority_score.py @@ -28,7 +28,7 @@ def test_priority(self): result = self.priority_calculator.calc_priority_score( vaf_dna=0.35, vaf_rna=0.33, - transcript_expr=12, + transcript_gene_expr=12, no_mismatch=1, score_mut=1.1, score_wt=10, @@ -39,7 +39,7 @@ def test_priority(self): result = self.priority_calculator.calc_priority_score( vaf_dna=None, vaf_rna=0.33, - transcript_expr=12, + transcript_gene_expr=12, no_mismatch=1, score_mut=1.1, score_wt=10, @@ -49,7 +49,7 @@ def test_priority(self): result = self.priority_calculator.calc_priority_score( vaf_dna=0.35, vaf_rna=None, - transcript_expr=12, + transcript_gene_expr=12, no_mismatch=1, score_mut=1.1, score_wt=10, @@ -59,7 +59,7 @@ def test_priority(self): result = self.priority_calculator.calc_priority_score( vaf_dna=None, vaf_rna=-1, - transcript_expr=12, + transcript_gene_expr=12, no_mismatch=1, score_mut=1.1, score_wt=10, @@ -69,7 +69,7 @@ def test_priority(self): result = self.priority_calculator.calc_priority_score( vaf_dna=0.35, vaf_rna=0.33, - transcript_expr=None, + transcript_gene_expr=None, no_mismatch=1, score_mut=1.1, score_wt=10, @@ -79,7 +79,7 @@ def test_priority(self): result = self.priority_calculator.calc_priority_score( vaf_dna=0.35, vaf_rna=0.33, - transcript_expr=None, + transcript_gene_expr=None, no_mismatch=1, score_mut=1.1, score_wt=10, From eb51862c27bd6c3c04b2bc728ed1a9b8d236e75c Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Thu, 23 Mar 2023 12:42:40 +0100 Subject: [PATCH 13/83] update version --- neofox/__init__.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index 0557bdef..cce70e3b 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b10" +VERSION = "1.1.0b11" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" From 24216b64ec985dab140f2da9155a349856f6c144 Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Wed, 29 Mar 2023 13:42:37 +0200 Subject: [PATCH 14/83] Hex R code --- MANIFEST.in | 5 ++++- neofox/__init__.py | 2 +- 2 files changed, 5 insertions(+), 2 deletions(-) diff --git a/MANIFEST.in b/MANIFEST.in index d93ba50a..2e11102a 100755 --- a/MANIFEST.in +++ b/MANIFEST.in @@ -13,4 +13,7 @@ include neofox/expression_imputation/tcga_cohort_code.tab include neofox/expression_imputation/tcga_exp_summary_modified.tab.gz.tbi include neofox/expression_imputation/tcga_exp_summary_modified.tab.gz include requirements.txt -include README.md \ No newline at end of file +include README.md +include neofox/published_features/hex/BLOSUM62.rda +include neofox/published_features/hex/EPItOMe_modified.R +include neofox/published_features/hex/hex.R diff --git a/neofox/__init__.py b/neofox/__init__.py index 0557bdef..cce70e3b 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b10" +VERSION = "1.1.0b11" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" From c0e45f3a51cb39aec808be73d50ebb8eaae8e3c2 Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Wed, 29 Mar 2023 13:57:20 +0200 Subject: [PATCH 15/83] Update libbz2-dev and documentation --- docs/source/02_installation.md | 2 +- docs/source/03_01_input_data.md | 2 +- docs/source/03_02_output_data.md | 2 +- docs/source/03_03_usage.md | 2 +- neofox/__init__.py | 2 +- 5 files changed, 5 insertions(+), 5 deletions(-) diff --git a/docs/source/02_installation.md b/docs/source/02_installation.md index 225f1556..cf20910c 100755 --- a/docs/source/02_installation.md +++ b/docs/source/02_installation.md @@ -37,7 +37,7 @@ Python 3.7 or 3.8 should be preinstalled. The libz compression development library is required. This can be installed in Ubuntu as follows: ``` -apt-get install libz-dev +apt-get install libbz2-dev ``` ### Install NeoFox diff --git a/docs/source/03_01_input_data.md b/docs/source/03_01_input_data.md index cdbd25c7..e84ee991 100644 --- a/docs/source/03_01_input_data.md +++ b/docs/source/03_01_input_data.md @@ -67,7 +67,7 @@ where: - Neoepitopes with a value for `alleleMhcI` are considered MHC-I neoepitopes, likewise neoepitopes with a value for `isoformMhcII` are considered MHC-II neoepitopes. Both fields cannot be provided for the same neoepitope. - If none of `alleleMhcI` and `isoformMhcII` are provided then the `patientIdentifier` is required and one neoepitope sharing the same sequence will be annotated for each MHC-I allele and MHC-II isoform according to the patient HLA type. -- If rnaExpression is not provided and the tumor type is given in the patient data, expression will be estimated by gene expression in TCGA cohort indicated in the `tumorType` in the patient data (see below). Please, not that this does not work for mouse data. Here, expression imputation is currently not supported. +- If the tumor type is given in the patient data (see below), gene expression in the matching TCGA cohort is annotated and expression-related are calculated based on imputated gene expression additionally (see [description of output data](03_02_output_data.md)). Please, note that this does not work for mouse data. Here, expression imputation is currently not supported. - If `dnaVariantAlleleFrequency` is given while `rnaVariantAlleleFrequency` is not given, the VAF in RNA will be estimated by the VAF in DNA. This means that feature scores that rely on the VAF in RNA will be calulated with the VAF in DNA. diff --git a/docs/source/03_02_output_data.md b/docs/source/03_02_output_data.md index 7e1abbff..5b5c2278 100755 --- a/docs/source/03_02_output_data.md +++ b/docs/source/03_02_output_data.md @@ -77,7 +77,7 @@ The following table describes each of the annotations in the output: | GeneratorRate_MHCII | sum of `GeneratorRate_CDN_MHCII` and `GeneratorRate_ADN_MHCII` | Generator rate | | Tcell_predictor | output score of T cell predictor model | Tcell predictor | | ImprovedBinder_MHCI | ratio of `NetMHCpan_MHCI_rank_bestRankWT` and `NetMHCpan_MHCI_rank_bestRank` > 1.2 | self-similarity | -| Selfsimilarity_MHCI_conserved_binder | score representing the similarity between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptideWT` For conservered binder only | self-similarity | +| Selfsimilarity_MHCI_conserved_binder | score representing the similarity between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptideWT` For conserved binder only | self-similarity | | Selfsimilarity_MHCI | score representing the similarity between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptide` | self-similarity | | Selfsimilarity_MHCII | score representing the similarity between `NetMHCIIpan_bestAffinity_peptide` and `NetMHCIIpan_bestAffinity_peptide` | self-similarity | | Number_of_mismatches_MCHI | number of amino acids that do no match between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptideWT` | Priority score | diff --git a/docs/source/03_03_usage.md b/docs/source/03_03_usage.md index 2604c7e8..c749d875 100755 --- a/docs/source/03_03_usage.md +++ b/docs/source/03_03_usage.md @@ -38,7 +38,7 @@ where: - `--patient-id`: patient identifier (*optional*, this is only relevant if the column `patientIdentifier` is missing in the candidate input file) **PLEASE NOTE THE FOLLOWING HINTS**: -- if all expression values related to a patient are NA or `rnaExpression` is not given in the input file but the tumor type has been provided in the patient file, imputated expression will be used for the relevant features +- If a tumor type has been provided in the patient file, imputated gene expression from TCGA will be annoated and expression-dependent features will be determined with imputated gene expression aswell. **EXAMPLE** This is an example to call NeoFox with a candidate file and obtaining the annotated neoantigen candidates in [tabular](03_02_output_data.md#tabular-format) format: diff --git a/neofox/__init__.py b/neofox/__init__.py index cce70e3b..cbeaa87f 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b11" +VERSION = "1.1.0b12" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" From 2a1f838c3e6cac56c35b20e493dc3dddb160c3e8 Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Wed, 29 Mar 2023 14:13:07 +0200 Subject: [PATCH 16/83] Update version of init --- neofox/__init__.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index cbeaa87f..945254b5 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b12" +VERSION = "1.1.0b13" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" From 6daf17c99cdb644dd3c3ee666c402ffa70121b73 Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Thu, 30 Mar 2023 14:22:59 +0200 Subject: [PATCH 17/83] Add new features to epitope mode and edit redundant code in expression.py --- neofox/__init__.py | 2 +- neofox/annotator/abstract_annotator.py | 5 +++- neofox/annotator/neoepitope_annotator.py | 4 +++- neofox/published_features/expression.py | 26 ++++----------------- neofox/published_features/priority_score.py | 14 ++++++++++- 5 files changed, 26 insertions(+), 25 deletions(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index 945254b5..93c04632 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b13" +VERSION = "1.1.0b14" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" diff --git a/neofox/annotator/abstract_annotator.py b/neofox/annotator/abstract_annotator.py index 20569016..c9158660 100644 --- a/neofox/annotator/abstract_annotator.py +++ b/neofox/annotator/abstract_annotator.py @@ -63,11 +63,13 @@ def get_additional_annotations_neoepitope_mhci( vaf_tumor_dna = neoantigen.dna_variant_allele_frequency vaf_tumor_rna = neoantigen.rna_variant_allele_frequency transcript_exp = neoantigen.rna_expression + gene_exp = neoantigen.imputed_gene_expression else: gene = epitope.gene vaf_tumor_dna = epitope.dna_variant_allele_frequency vaf_tumor_rna = epitope.rna_variant_allele_frequency transcript_exp = epitope.rna_expression + gene_exp = epitope.imputed_gene_expression epitope.neofox_annotations.annotations.extend( BestAndMultipleBinder.get_annotations_epitope_mhci(epitope=epitope) + @@ -94,7 +96,8 @@ def get_additional_annotations_neoepitope_mhci( epitope.neofox_annotations.annotations.extend( self.priority_score_calculator.get_annotations_epitope_mhci( - epitope=epitope, vaf_rna=vaf_tumor_rna, vaf_tumor=vaf_tumor_dna, transcript_exp=transcript_exp)) + epitope=epitope, vaf_rna=vaf_tumor_rna, vaf_tumor=vaf_tumor_dna, + transcript_exp=transcript_exp, gene_exp=gene_exp)) if self.organism == ORGANISM_HOMO_SAPIENS: epitope.neofox_annotations.annotations.extend( diff --git a/neofox/annotator/neoepitope_annotator.py b/neofox/annotator/neoepitope_annotator.py index 0fec9f51..32f7602c 100755 --- a/neofox/annotator/neoepitope_annotator.py +++ b/neofox/annotator/neoepitope_annotator.py @@ -72,6 +72,8 @@ def get_annotated_neoepitope(self, neoepitope: PredictedEpitope) -> PredictedEpi resources=self.resources_versions, annotations=[] ) + self.expression_calculator = Expression() + expression_annotation = self.expression_calculator.get_annotations(neoantigen=neoepitope) # if the WT is not provided it searches for the closest match in the proteome if neoepitope.wild_type_peptide is None or neoepitope.wild_type_peptide == '': @@ -80,7 +82,7 @@ def get_annotated_neoepitope(self, neoepitope: PredictedEpitope) -> PredictedEpi # Runs netmhcpan, netmhc2pan, mixmhcpred and mixmhc2prd in parallel annotated_neoepitope = self.neoepitope_mhc_binding_annotator.get_mhc_binding_annotations(neoepitope=neoepitope) - + annotated_neoepitope.neofox_annotations.annotations.extend(expression_annotation) has_mhc1 = annotated_neoepitope.allele_mhc_i is not None and annotated_neoepitope.allele_mhc_i.name if has_mhc1: diff --git a/neofox/published_features/expression.py b/neofox/published_features/expression.py index da2ce78a..07f4d7a3 100755 --- a/neofox/published_features/expression.py +++ b/neofox/published_features/expression.py @@ -27,7 +27,7 @@ class Expression: @staticmethod def _get_expression_annotation( - transcript_expression: float, vaf_rna: float + transcript_gene_expression: float, vaf_rna: float ) -> float: """ This function calculates the product of VAF in RNA and transcript expression @@ -36,7 +36,7 @@ def _get_expression_annotation( expression_mut = None try: expression_mut = ( - transcript_expression * vaf_rna + transcript_gene_expression * vaf_rna if vaf_rna is not None and vaf_rna >= 0.0 else None ) @@ -44,22 +44,6 @@ def _get_expression_annotation( pass return expression_mut - @staticmethod - def _get_geneExpression_annotation( - imputed_geneExpression: float, vaf_rna: float - ) -> float: - imputed_geneExpression_mut = None - try: - imputed_geneExpression_mut = ( - imputed_geneExpression * vaf_rna - if (vaf_rna is not None and vaf_rna >= 0.0) - #and (Patient.tumor_type is not None and Patient.tumor_type != "") - else None - ) - except(TypeError, ValueError): - pass - return imputed_geneExpression_mut - def get_annotations(self, neoantigen: Neoantigen) -> List[Annotation]: vaf = neoantigen.rna_variant_allele_frequency @@ -69,8 +53,8 @@ def get_annotations(self, neoantigen: Neoantigen) -> List[Annotation]: return [ AnnotationFactory.build_annotation( name="Mutated_rnaExpression", value=self._get_expression_annotation( - transcript_expression=neoantigen.rna_expression, vaf_rna=vaf)), + transcript_gene_expression=neoantigen.rna_expression, vaf_rna=vaf)), AnnotationFactory.build_annotation( - name="Mutated_imputedGeneExpression", value=self._get_geneExpression_annotation( - imputed_geneExpression=neoantigen.imputed_gene_expression, vaf_rna=vaf)) + name="Mutated_imputedGeneExpression", value=self._get_expression_annotation( + transcript_gene_expression=neoantigen.imputed_gene_expression, vaf_rna=vaf)) ] diff --git a/neofox/published_features/priority_score.py b/neofox/published_features/priority_score.py index 4e5e8897..49a120dc 100755 --- a/neofox/published_features/priority_score.py +++ b/neofox/published_features/priority_score.py @@ -140,7 +140,7 @@ def get_annotations( ] return annotations - def get_annotations_epitope_mhci(self, epitope: PredictedEpitope, vaf_tumor, transcript_exp, vaf_rna) -> \ + def get_annotations_epitope_mhci(self, epitope: PredictedEpitope, vaf_tumor, transcript_exp, vaf_rna, gene_exp) -> \ List[Annotation]: return [ AnnotationFactory.build_annotation( @@ -155,4 +155,16 @@ def get_annotations_epitope_mhci(self, epitope: PredictedEpitope, vaf_tumor, tra mut_not_in_prot=bool(EpitopeHelper.get_annotation_by_name( epitope.neofox_annotations.annotations, name='mutation_not_found_in_proteome'))), name='Priority_score'), + AnnotationFactory.build_annotation( + value=self.calc_priority_score( + vaf_dna=vaf_tumor, + vaf_rna=vaf_rna, + transcript_gene_expr=gene_exp, + no_mismatch=int(EpitopeHelper.get_annotation_by_name( + epitope.neofox_annotations.annotations, name='number_of_mismatches')), + score_mut=epitope.rank_mutated, + score_wt=epitope.rank_wild_type, + mut_not_in_prot=bool(EpitopeHelper.get_annotation_by_name( + epitope.neofox_annotations.annotations, name='mutation_not_found_in_proteome'))), + name='Priority_score_imputed'), ] From 708af46eae723b24efde8f19f65174673d36093c Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Mon, 3 Apr 2023 10:13:56 +0200 Subject: [PATCH 18/83] Added external annotations to epitope output of neoantigen mode. Fixed naming of patientIdentifier column (closes #285). --- neofox/model/conversion.py | 4 +++- 1 file changed, 3 insertions(+), 1 deletion(-) diff --git a/neofox/model/conversion.py b/neofox/model/conversion.py index 757efacf..2e1df145 100755 --- a/neofox/model/conversion.py +++ b/neofox/model/conversion.py @@ -184,7 +184,7 @@ def annotations2epitopes_table(neoantigens: List[Neoantigen], mhc: str) -> pd.Da patient_identifier = n.patient_identifier epitopes = n.neoepitopes_mhc_i if mhc == MHC_I else n.neoepitopes_mhc_i_i epitopes_temp_df = ModelConverter._objects2dataframe(epitopes) - epitopes_temp_df['patient_identifier'] = patient_identifier + epitopes_temp_df['patientIdentifier'] = patient_identifier # adapts output table depending on MHC type if mhc == MHC_I: @@ -199,6 +199,8 @@ def annotations2epitopes_table(neoantigens: List[Neoantigen], mhc: str) -> pd.Da annotations_dfs = [] for e in epitopes: annotations = [a.to_dict() for a in e.neofox_annotations.annotations] + # add external annotations also to epitope table + annotations.extend([a.to_dict() for a in n.external_annotations]) annotations_temp_df = (pd.DataFrame(annotations).set_index("name").transpose()) annotations_dfs.append(annotations_temp_df) if len(annotations_dfs) > 0: From 394a71ac51ff8fc20d1462b748bece29894dbf3f Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Tue, 4 Apr 2023 15:51:52 +0200 Subject: [PATCH 19/83] Removed hex files in MANIFEST.in file as discussed in issue #280 --- MANIFEST.in | 6 ------ 1 file changed, 6 deletions(-) diff --git a/MANIFEST.in b/MANIFEST.in index 2e11102a..0da8967c 100755 --- a/MANIFEST.in +++ b/MANIFEST.in @@ -6,14 +6,8 @@ include neofox/published_features/Tcell_predictor/SIRdata.mat include neofox/published_features/Tcell_predictor/Classifier.pickle include neofox/references/install_r_dependencies.R include neofox/references/h2_database_allele_list.csv -include neofox/published_features/hex/BLOSUM62.rda -include neofox/published_features/hex/EPItOMe_modified.R -include neofox/published_features/hex/hex.R include neofox/expression_imputation/tcga_cohort_code.tab include neofox/expression_imputation/tcga_exp_summary_modified.tab.gz.tbi include neofox/expression_imputation/tcga_exp_summary_modified.tab.gz include requirements.txt include README.md -include neofox/published_features/hex/BLOSUM62.rda -include neofox/published_features/hex/EPItOMe_modified.R -include neofox/published_features/hex/hex.R From 4d51580378c616b25897f2d23c60ed238731e35b Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Tue, 4 Apr 2023 16:33:56 +0200 Subject: [PATCH 20/83] Updated version --- neofox/__init__.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index 945254b5..2cc82834 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b13" +VERSION = "1.1.0b15" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" From 94c8cfa4a0219f7fbb17fd3b6d2107e9da74cdb6 Mon Sep 17 00:00:00 2001 From: Franziska Lang Date: Tue, 4 Apr 2023 17:46:10 +0200 Subject: [PATCH 21/83] replace None with NA value in external annotation in epitope table --- neofox/model/conversion.py | 5 +++-- 1 file changed, 3 insertions(+), 2 deletions(-) diff --git a/neofox/model/conversion.py b/neofox/model/conversion.py index 2e1df145..4a1fc0e5 100755 --- a/neofox/model/conversion.py +++ b/neofox/model/conversion.py @@ -206,15 +206,16 @@ def annotations2epitopes_table(neoantigens: List[Neoantigen], mhc: str) -> pd.Da if len(annotations_dfs) > 0: annotations_df = pd.concat(annotations_dfs, sort=True).reset_index() del annotations_df["index"] - + # puts together both data frames epitopes_temp_df = pd.concat([epitopes_temp_df, annotations_df], axis=1) - + epitopes_temp_df.replace({None: NOT_AVAILABLE_VALUE}, inplace=True) epitopes_dfs.append(epitopes_temp_df) # concatenates all together epitopes_df = pd.concat(epitopes_dfs) + epitopes_df.replace('None', NOT_AVAILABLE_VALUE, inplace=True) return epitopes_df From 2d201fd26e68c84d7efaf77fe2cf9912f6ac9084 Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Tue, 4 Apr 2023 19:14:18 +0200 Subject: [PATCH 22/83] Remove lines in MANIFEST file --- MANIFEST.in | 6 ------ neofox/__init__.py | 2 +- 2 files changed, 1 insertion(+), 7 deletions(-) diff --git a/MANIFEST.in b/MANIFEST.in index 2e11102a..0da8967c 100755 --- a/MANIFEST.in +++ b/MANIFEST.in @@ -6,14 +6,8 @@ include neofox/published_features/Tcell_predictor/SIRdata.mat include neofox/published_features/Tcell_predictor/Classifier.pickle include neofox/references/install_r_dependencies.R include neofox/references/h2_database_allele_list.csv -include neofox/published_features/hex/BLOSUM62.rda -include neofox/published_features/hex/EPItOMe_modified.R -include neofox/published_features/hex/hex.R include neofox/expression_imputation/tcga_cohort_code.tab include neofox/expression_imputation/tcga_exp_summary_modified.tab.gz.tbi include neofox/expression_imputation/tcga_exp_summary_modified.tab.gz include requirements.txt include README.md -include neofox/published_features/hex/BLOSUM62.rda -include neofox/published_features/hex/EPItOMe_modified.R -include neofox/published_features/hex/hex.R diff --git a/neofox/__init__.py b/neofox/__init__.py index 93c04632..2cc82834 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b14" +VERSION = "1.1.0b15" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" From 269e6c25c3802c2f9fb669910f369f98564fc67b Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Thu, 6 Apr 2023 12:14:33 +0200 Subject: [PATCH 23/83] Insert right values of Neoantigen object in Epitope Output and insert mutated_xmer column --- neofox/__init__.py | 2 +- neofox/annotator/abstract_annotator.py | 17 ++++++++++++++++- neofox/annotator/neoantigen_annotator.py | 3 +-- neofox/model/neoantigen.py | 3 ++- 4 files changed, 20 insertions(+), 5 deletions(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index 2cc82834..2ef0f934 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b15" +VERSION = "1.1.0b16" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" diff --git a/neofox/annotator/abstract_annotator.py b/neofox/annotator/abstract_annotator.py index c9158660..8498dc46 100644 --- a/neofox/annotator/abstract_annotator.py +++ b/neofox/annotator/abstract_annotator.py @@ -57,7 +57,7 @@ def __init__( def get_additional_annotations_neoepitope_mhci( self, epitope: PredictedEpitope, neoantigen: Neoantigen = None) -> PredictedEpitope: - + ''' if neoantigen is not None: gene = neoantigen.gene vaf_tumor_dna = neoantigen.dna_variant_allele_frequency @@ -70,6 +70,21 @@ def get_additional_annotations_neoepitope_mhci( vaf_tumor_rna = epitope.rna_variant_allele_frequency transcript_exp = epitope.rna_expression gene_exp = epitope.imputed_gene_expression + ''' + if neoantigen is not None: + epitope.gene = neoantigen.gene + epitope.patient_identifier = neoantigen.patient_identifier + epitope.rna_expression = neoantigen.rna_expression + epitope.imputed_gene_expression = neoantigen.imputed_gene_expression + epitope.dna_variant_allele_frequency = neoantigen.dna_variant_allele_frequency + epitope.rna_variant_allele_frequency = neoantigen.rna_variant_allele_frequency + epitope.mutated_xmer = neoantigen.mutated_xmer + + gene = epitope.gene + vaf_tumor_dna = epitope.dna_variant_allele_frequency + vaf_tumor_rna = epitope.rna_variant_allele_frequency + transcript_exp = epitope.rna_expression + gene_exp = epitope.imputed_gene_expression epitope.neofox_annotations.annotations.extend( BestAndMultipleBinder.get_annotations_epitope_mhci(epitope=epitope) + diff --git a/neofox/annotator/neoantigen_annotator.py b/neofox/annotator/neoantigen_annotator.py index 812fd0ce..ea0be963 100755 --- a/neofox/annotator/neoantigen_annotator.py +++ b/neofox/annotator/neoantigen_annotator.py @@ -237,8 +237,7 @@ def get_annotated_neoantigen(self, neoantigen: Neoantigen, patient: Patient, wit # annotate neoepitopes if with_all_neoepitopes: neoantigen.neoepitopes_mhc_i = [ - self.get_additional_annotations_neoepitope_mhci( - epitope=e, neoantigen=neoantigen) + self.get_additional_annotations_neoepitope_mhci(epitope=e, neoantigen=neoantigen) for e in neoantigen.neoepitopes_mhc_i] neoantigen.neoepitopes_mhc_i_i = [ self.get_additional_annotations_neoepitope_mhcii(epitope=e) for e in neoantigen.neoepitopes_mhc_i_i] diff --git a/neofox/model/neoantigen.py b/neofox/model/neoantigen.py index b4b925fd..84d75846 100755 --- a/neofox/model/neoantigen.py +++ b/neofox/model/neoantigen.py @@ -259,7 +259,8 @@ class PredictedEpitope(betterproto.Message): dna_variant_allele_frequency: float = betterproto.float_field(15) # *Variant allele frequency from the RNA. Range [0.0, 1.0] rna_variant_allele_frequency: float = betterproto.float_field(16) - + # *Amino acid sequence of the neoantigen candidate (IUPAC 1 letter codes) + mutated_xmer: str = betterproto.string_field(17) @dataclass class Neoantigen(betterproto.Message): From 29f0a21aad5d7515b80724b8b7bc8c8f314246b7 Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Thu, 20 Apr 2023 13:00:18 +0200 Subject: [PATCH 24/83] Fix the code for the correct outputs in both MHC --- neofox/__init__.py | 2 +- neofox/annotator/abstract_annotator.py | 20 +++----------------- neofox/model/conversion.py | 17 +++++++++++++++-- neofox/model/neoantigen.py | 2 -- 4 files changed, 19 insertions(+), 22 deletions(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index 2ef0f934..1cb1c693 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b16" +VERSION = "1.1.0b17" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" diff --git a/neofox/annotator/abstract_annotator.py b/neofox/annotator/abstract_annotator.py index 8498dc46..5f0307ee 100644 --- a/neofox/annotator/abstract_annotator.py +++ b/neofox/annotator/abstract_annotator.py @@ -57,7 +57,7 @@ def __init__( def get_additional_annotations_neoepitope_mhci( self, epitope: PredictedEpitope, neoantigen: Neoantigen = None) -> PredictedEpitope: - ''' + if neoantigen is not None: gene = neoantigen.gene vaf_tumor_dna = neoantigen.dna_variant_allele_frequency @@ -70,21 +70,6 @@ def get_additional_annotations_neoepitope_mhci( vaf_tumor_rna = epitope.rna_variant_allele_frequency transcript_exp = epitope.rna_expression gene_exp = epitope.imputed_gene_expression - ''' - if neoantigen is not None: - epitope.gene = neoantigen.gene - epitope.patient_identifier = neoantigen.patient_identifier - epitope.rna_expression = neoantigen.rna_expression - epitope.imputed_gene_expression = neoantigen.imputed_gene_expression - epitope.dna_variant_allele_frequency = neoantigen.dna_variant_allele_frequency - epitope.rna_variant_allele_frequency = neoantigen.rna_variant_allele_frequency - epitope.mutated_xmer = neoantigen.mutated_xmer - - gene = epitope.gene - vaf_tumor_dna = epitope.dna_variant_allele_frequency - vaf_tumor_rna = epitope.rna_variant_allele_frequency - transcript_exp = epitope.rna_expression - gene_exp = epitope.imputed_gene_expression epitope.neofox_annotations.annotations.extend( BestAndMultipleBinder.get_annotations_epitope_mhci(epitope=epitope) + @@ -121,7 +106,8 @@ def get_additional_annotations_neoepitope_mhci( return epitope - def get_additional_annotations_neoepitope_mhcii(self, epitope: PredictedEpitope) -> PredictedEpitope: + def get_additional_annotations_neoepitope_mhcii( + self, epitope: PredictedEpitope) -> PredictedEpitope: epitope.neofox_annotations.annotations.extend( self.amplitude.get_annotations_epitope_mhcii(epitope=epitope) + diff --git a/neofox/model/conversion.py b/neofox/model/conversion.py index 757efacf..1a0c9a96 100755 --- a/neofox/model/conversion.py +++ b/neofox/model/conversion.py @@ -181,10 +181,23 @@ def annotations2epitopes_table(neoantigens: List[Neoantigen], mhc: str) -> pd.Da epitopes_dfs = [] for n in neoantigens: # parses epitopes from a neoantigen into a data frame - patient_identifier = n.patient_identifier + #patient_identifier = n.patient_identifier + #gene = n.gene + #rna_expression = n.rna_expression + #imputed_gene_expression = n.imputed_gene_expression + #dna_vaf = n.dna_variant_allele_frequency + #rna_vaf = n.rna_variant_allele_frequency + #mutated_xmer = n.mutated_xmer + epitopes = n.neoepitopes_mhc_i if mhc == MHC_I else n.neoepitopes_mhc_i_i epitopes_temp_df = ModelConverter._objects2dataframe(epitopes) - epitopes_temp_df['patient_identifier'] = patient_identifier + epitopes_temp_df['patientIdentifier'] = n.patient_identifier + epitopes_temp_df['gene'] = n.gene + epitopes_temp_df['rnaExpression'] = n.rna_expression + epitopes_temp_df['imputedGeneExpression'] = n.imputed_gene_expression + epitopes_temp_df['dnaVariantAlleleFrequency'] = n.dna_vaf + epitopes_temp_df['rnaVariantAlleleFrequency'] = n.rna_vaf + epitopes_temp_df['mutatedXmer'] = n.mutated_xmer # adapts output table depending on MHC type if mhc == MHC_I: diff --git a/neofox/model/neoantigen.py b/neofox/model/neoantigen.py index 84d75846..8d362e5b 100755 --- a/neofox/model/neoantigen.py +++ b/neofox/model/neoantigen.py @@ -259,8 +259,6 @@ class PredictedEpitope(betterproto.Message): dna_variant_allele_frequency: float = betterproto.float_field(15) # *Variant allele frequency from the RNA. Range [0.0, 1.0] rna_variant_allele_frequency: float = betterproto.float_field(16) - # *Amino acid sequence of the neoantigen candidate (IUPAC 1 letter codes) - mutated_xmer: str = betterproto.string_field(17) @dataclass class Neoantigen(betterproto.Message): From 6474ac4f7eb5f4239fc6d2d40924ff878a320fff Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Thu, 20 Apr 2023 13:06:44 +0200 Subject: [PATCH 25/83] Correct output in both epitope outputs --- neofox/model/conversion.py | 8 -------- 1 file changed, 8 deletions(-) diff --git a/neofox/model/conversion.py b/neofox/model/conversion.py index 1a0c9a96..9b418c56 100755 --- a/neofox/model/conversion.py +++ b/neofox/model/conversion.py @@ -181,14 +181,6 @@ def annotations2epitopes_table(neoantigens: List[Neoantigen], mhc: str) -> pd.Da epitopes_dfs = [] for n in neoantigens: # parses epitopes from a neoantigen into a data frame - #patient_identifier = n.patient_identifier - #gene = n.gene - #rna_expression = n.rna_expression - #imputed_gene_expression = n.imputed_gene_expression - #dna_vaf = n.dna_variant_allele_frequency - #rna_vaf = n.rna_variant_allele_frequency - #mutated_xmer = n.mutated_xmer - epitopes = n.neoepitopes_mhc_i if mhc == MHC_I else n.neoepitopes_mhc_i_i epitopes_temp_df = ModelConverter._objects2dataframe(epitopes) epitopes_temp_df['patientIdentifier'] = n.patient_identifier From bbc676858921a2bf80da23f5bbbefb648dd7f78c Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Thu, 20 Apr 2023 14:20:43 +0200 Subject: [PATCH 26/83] fix errors in vaf --- neofox/__init__.py | 2 +- neofox/model/conversion.py | 4 ++-- 2 files changed, 3 insertions(+), 3 deletions(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index 1cb1c693..7a160397 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b17" +VERSION = "1.1.0b18" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" diff --git a/neofox/model/conversion.py b/neofox/model/conversion.py index 0774265a..00bd12a7 100755 --- a/neofox/model/conversion.py +++ b/neofox/model/conversion.py @@ -188,8 +188,8 @@ def annotations2epitopes_table(neoantigens: List[Neoantigen], mhc: str) -> pd.Da epitopes_temp_df['gene'] = n.gene epitopes_temp_df['rnaExpression'] = n.rna_expression epitopes_temp_df['imputedGeneExpression'] = n.imputed_gene_expression - epitopes_temp_df['dnaVariantAlleleFrequency'] = n.dna_vaf - epitopes_temp_df['rnaVariantAlleleFrequency'] = n.rna_vaf + epitopes_temp_df['dnaVariantAlleleFrequency'] = n.dna_variant_allele_frequency + epitopes_temp_df['rnaVariantAlleleFrequency'] = n.rna_variant_allele_frequency epitopes_temp_df['mutatedXmer'] = n.mutated_xmer # adapts output table depending on MHC type From 2472cc116df86289f64b1e0a77e51b6c8cf0d94f Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Fri, 28 Apr 2023 13:43:26 +0200 Subject: [PATCH 27/83] Epitope mode keep external annotations. Current problem: column externalAnnotations is incorrectly added to the epitopes table --- neofox/command_line.py | 7 ++-- neofox/model/conversion.py | 74 ++++++++++++++++------------------- neofox/model/factories.py | 6 ++- neofox/model/neoantigen.proto | 4 ++ neofox/model/neoantigen.py | 2 + 5 files changed, 47 insertions(+), 46 deletions(-) diff --git a/neofox/command_line.py b/neofox/command_line.py index ecbc3d5e..765ef1a5 100755 --- a/neofox/command_line.py +++ b/neofox/command_line.py @@ -336,7 +336,8 @@ def neofox_epitope_cli(): neoepitopes, patients = _read_data_epitopes( input_file, patients_data, - reference_folder.get_mhc_database()) + reference_folder.get_mhc_database(), + organism) # run annotations annotated_neoepitopes = NeoFoxEpitope( @@ -360,7 +361,7 @@ def neofox_epitope_cli(): def _read_data_epitopes( - input_file, patients_data, mhc_database: MhcDatabase) -> Tuple[List[PredictedEpitope], List[Patient]]: + input_file, patients_data, mhc_database: MhcDatabase, organism: str) -> Tuple[List[PredictedEpitope], List[Patient]]: # parse patient data patients = [] @@ -372,7 +373,7 @@ def _read_data_epitopes( # parse the neoantigen candidate data if input_file.endswith('.txt') or input_file.endswith('.tsv'): logger.info("Parsing candidate neoepitopes from: {}".format(input_file)) - neoepitopes = ModelConverter.parse_candidate_neoepitopes_file(input_file, mhc_database) + neoepitopes = ModelConverter.parse_candidate_neoepitopes_file(input_file, mhc_database, organism) logger.info("Loaded {} candidate neoepitopes".format(len(neoepitopes))) # TODO: add support for input in JSON format #elif input_file.endswith('.json') : diff --git a/neofox/model/conversion.py b/neofox/model/conversion.py index 4a1fc0e5..c9130c47 100755 --- a/neofox/model/conversion.py +++ b/neofox/model/conversion.py @@ -29,8 +29,13 @@ Neoantigen, Patient, PredictedEpitope, + Annotation, +) +from neofox.model.factories import ( + PatientFactory, + NeoantigenFactory, + NeoepitopeFactory, ) -from neofox.model.factories import PatientFactory, NeoantigenFactory from neofox.references.references import MhcDatabase @@ -63,7 +68,7 @@ def parse_candidate_file(candidate_file: str) -> List[Neoantigen]: return neoantigens @staticmethod - def parse_candidate_neoepitopes_file(candidate_file: str, mhc_database: MhcDatabase) -> List[PredictedEpitope]: + def parse_candidate_neoepitopes_file(candidate_file: str, mhc_database: MhcDatabase, organism: str) -> List[PredictedEpitope]: data = pd.read_csv( candidate_file, sep="\t", # NOTE: forces the types of every column to avoid pandas setting the wrong type for corner cases @@ -82,7 +87,7 @@ def parse_candidate_neoepitopes_file(candidate_file: str, mhc_database: MhcDatab # NOTE: this is the support for the NeoFox format data = data.replace({np.nan: None}) - neoepitopes = ModelConverter._neoepitopes_csv2objects(data, mhc_database) + neoepitopes = ModelConverter._neoepitopes_csv2objects(data, mhc_database, organism) return neoepitopes @@ -241,6 +246,8 @@ def annotated_neoepitopes2epitopes_table(neoepitopes: List[PredictedEpitope], mh annotations_dfs = [] for e in neoepitopes: annotations = [a.to_dict() for a in e.neofox_annotations.annotations] + # add external annotations to output table + annotations.extend([a.to_dict() for a in e.external_annotations]) annotations_temp_df = (pd.DataFrame(annotations).set_index("name").transpose()) annotations_dfs.append(annotations_temp_df) if len(annotations_dfs) > 0: @@ -250,6 +257,8 @@ def annotated_neoepitopes2epitopes_table(neoepitopes: List[PredictedEpitope], mh # puts together both data frames epitopes_df = pd.concat([epitopes_df, annotations_df], axis=1) + # has to be dropped otherwise a column containing all external annotations will exist + epitopes_df.drop(["externalAnnotations"], axis=1, inplace=True) # replace None by NA epitopes_df.replace({None: NOT_AVAILABLE_VALUE}, inplace=True) @@ -311,7 +320,7 @@ def _neoantigens_csv2objects(dataframe: pd.DataFrame) -> List[Neoantigen]: return neoantigens @staticmethod - def _neoepitopes_csv2objects(dataframe: pd.DataFrame, mhc_database: MhcDatabase) -> List[PredictedEpitope]: + def _neoepitopes_csv2objects(dataframe: pd.DataFrame, mhc_database: MhcDatabase, organism: str) -> List[PredictedEpitope]: """transforms an patients CSV into a list of objects""" neoepitopes = [] mhc_parser = MhcParser.get_mhc_parser(mhc_database) @@ -327,7 +336,7 @@ def _neoepitopes_csv2objects(dataframe: pd.DataFrame, mhc_database: MhcDatabase) external_annotations.pop("affinityWildType", None) external_annotations.pop("rankWildType", None) external_annotations.pop("alleleMhcI", None) - external_annotations.pop("alleleMhcII", None) + external_annotations.pop("isoformMhcII", None) external_annotations.pop("position", None) external_annotations.pop("patientIdentifier", None) external_annotations.pop("gene", None) @@ -338,45 +347,28 @@ def _neoepitopes_csv2objects(dataframe: pd.DataFrame, mhc_database: MhcDatabase) mhci_allele = neoepitope_dict.get("alleleMhcI") mhcii_isoform = neoepitope_dict.get("isoformMhcII") patient_id = neoepitope_dict.get("patientIdentifier") - if mhci_allele is not None and mhci_allele != '': - neoepitope = PredictedEpitope( - mutated_peptide=neoepitope_dict.get("mutatedPeptide"), - wild_type_peptide=neoepitope_dict.get("wildTypePeptide"), - patient_identifier=patient_id, - allele_mhc_i=mhc_parser.parse_mhc_allele(mhci_allele), - gene=neoepitope_dict.get("gene"), - rna_expression=neoepitope_dict.get("rnaExpression"), - rna_variant_allele_frequency=neoepitope_dict.get("rnaVariantAlleleFrequency"), - dna_variant_allele_frequency=neoepitope_dict.get("dnaVariantAlleleFrequency"), - imputed_gene_expression=neoepitope_dict.get("imputedGeneExpression"), - ) - elif mhcii_isoform is not None and mhcii_isoform != '': - neoepitope = PredictedEpitope( - mutated_peptide=neoepitope_dict.get("mutatedPeptide"), - wild_type_peptide=neoepitope_dict.get("wildTypePeptide"), - patient_identifier=patient_id, - isoform_mhc_i_i=mhc_parser.parse_mhc2_isoform(mhcii_isoform), - gene=neoepitope_dict.get("gene"), - rna_expression=neoepitope_dict.get("rnaExpression"), - rna_variant_allele_frequency=neoepitope_dict.get("rnaVariantAlleleFrequency"), - dna_variant_allele_frequency=neoepitope_dict.get("dnaVariantAlleleFrequency"), - imputed_gene_expression=neoepitope_dict.get("imputedGeneExpression"), - ) - elif patient_id is not None and patient_id != '': - neoepitope = PredictedEpitope( - mutated_peptide=neoepitope_dict.get("mutatedPeptide"), - wild_type_peptide=neoepitope_dict.get("wildTypePeptide"), - patient_identifier=patient_id, - gene=neoepitope_dict.get("gene"), - rna_expression=neoepitope_dict.get("rnaExpression"), - rna_variant_allele_frequency=neoepitope_dict.get("rnaVariantAlleleFrequency"), - dna_variant_allele_frequency=neoepitope_dict.get("dnaVariantAlleleFrequency"), - imputed_gene_expression=neoepitope_dict.get("imputedGeneExpression"), - ) - else: + + # check if any source for allele inference is given otherwise raise error + if all(var is None or var == '' for var in [mhci_allele, mhcii_isoform, patient_id]): raise ValueError( "Found an epitope without MHC-I allele, MHC-II isoform or patiend identifier: {}".format( neoepitope_dict)) + neoepitope = NeoepitopeFactory.build_neoepitope( + organism=organism, + mutated_peptide=neoepitope_dict.get("mutatedPeptide"), + wild_type_peptide=neoepitope_dict.get("wildTypePeptide"), + patient_identifier=patient_id, + gene=neoepitope_dict.get("gene"), + rna_expression=neoepitope_dict.get("rnaExpression"), + rna_variant_allele_frequency=neoepitope_dict.get("rnaVariantAlleleFrequency"), + dna_variant_allele_frequency=neoepitope_dict.get("dnaVariantAlleleFrequency"), + imputed_gene_expression=neoepitope_dict.get("imputedGeneExpression"), + allele_mhc_i=mhci_allele, + isoform_mhc_i_i=mhcii_isoform, + mhc_database=mhc_database, + **external_annotations + ) + neoepitopes.append(neoepitope) return neoepitopes diff --git a/neofox/model/factories.py b/neofox/model/factories.py index 6b6ce7ff..13ded262 100755 --- a/neofox/model/factories.py +++ b/neofox/model/factories.py @@ -158,8 +158,10 @@ def build_neoepitope(mutated_peptide=None, wild_type_peptide=None, patient_ident # parse MHC alleles and isoforms mhc_parser = MhcParser.get_mhc_parser(mhc_database) - neoepitope.allele_mhc_i = mhc_parser.parse_mhc_allele(allele_mhc_i) if allele_mhc_i else None - neoepitope.isoform_mhc_i_i = mhc_parser.parse_mhc2_isoform(isoform_mhc_i_i) if isoform_mhc_i_i else None + if allele_mhc_i: + neoepitope.allele_mhc_i = mhc_parser.parse_mhc_allele(allele_mhc_i) + if isoform_mhc_i_i: + neoepitope.isoform_mhc_i_i = mhc_parser.parse_mhc2_isoform(isoform_mhc_i_i) external_annotation_names = dict.fromkeys( nam for nam in kw.keys() if stringcase.snakecase(nam) not in set(Neoantigen.__annotations__.keys())) diff --git a/neofox/model/neoantigen.proto b/neofox/model/neoantigen.proto index 572fad93..58c8c12f 100755 --- a/neofox/model/neoantigen.proto +++ b/neofox/model/neoantigen.proto @@ -335,6 +335,10 @@ message PredictedEpitope { Variant allele frequency from the RNA. Range [0.0, 1.0] */ float rnaVariantAlleleFrequency = 16; + /** + External annotations for neoepitope mode. + */ + repeated Annotation externalAnnotations = 17; } /** diff --git a/neofox/model/neoantigen.py b/neofox/model/neoantigen.py index b4b925fd..5537d60d 100755 --- a/neofox/model/neoantigen.py +++ b/neofox/model/neoantigen.py @@ -259,6 +259,8 @@ class PredictedEpitope(betterproto.Message): dna_variant_allele_frequency: float = betterproto.float_field(15) # *Variant allele frequency from the RNA. Range [0.0, 1.0] rna_variant_allele_frequency: float = betterproto.float_field(16) + # *External annotations for neoepitope mode. + external_annotations: List["Annotation"] = betterproto.message_field(17) @dataclass From faf1d37b4e87ed74b37198af3d9678cb83b4e780 Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Thu, 4 May 2023 10:07:03 +0200 Subject: [PATCH 28/83] correct and add integration tests --- docs/source/03_02_output_data.md | 12 ++++++------ neofox/__init__.py | 2 +- .../integration_tests/test_neoantigen_fitness.py | 2 +- neofox/tests/integration_tests/test_neofox.py | 13 +++++++++++++ .../tests/integration_tests/test_neofox_epitope.py | 4 +++- 5 files changed, 24 insertions(+), 9 deletions(-) diff --git a/docs/source/03_02_output_data.md b/docs/source/03_02_output_data.md index e97db3b6..8645d740 100755 --- a/docs/source/03_02_output_data.md +++ b/docs/source/03_02_output_data.md @@ -285,17 +285,17 @@ The following table describes each of the annotations in the output: | affinityWildType | NetMHCpan / NetMHCIIpan affinity score of the wild type peptide for MHC-I or MHC-II neoepitopes respectively | MHC-I / MHC-II binding with netMHCpan / netMHCIIpan | | rankMutated | NetMHCpan / NetMHCIIpan rank of the mutated peptide for MHC-I or MHC-II neoepitopes respectively | MHC-I / MHC-II binding with netMHCpan / netMHCIIpan | | rankWildType | NetMHCpan / NetMHCIIpan rank of the wild type peptide for MHC-I or MHC-II neoepitopes respectively | MHC-I / MHC-II binding with netMHCpan / netMHCIIpan | -| MixMHCpred_score | MixMHCpred score of the mutated peptide for MHC-I neoepitopes | MHC-I binding with mixMHCpred | +| MixMHCpred_score | MixMHCpred score of the mutated peptide for MHC-I neoepitopes | MHC-I binding with mixMHCpred | | MixMHCpred_rank | MixMHCpred rank of the mutated peptide for MHC-I neoepitopes | MHC-I binding with mixMHCpred | -| MixMHCpred_WT_score | MixMHCpred score of the wild type peptide for MHC-I neoepitopes | MHC-I binding with mixMHCpred | +| MixMHCpred_WT_score | MixMHCpred score of the wild type peptide for MHC-I neoepitopes | MHC-I binding with mixMHCpred | | MixMHCpred_WT_rank | MixMHCpred rank of the wild type peptide for MHC-I neoepitopes | MHC-I binding with mixMHCpred | -| MixMHC2pred_score | MixMHC2pred score of the mutated peptide for MHC-II neoepitopes | MHC-II binding with mixMHC2pred | +| MixMHC2pred_score | MixMHC2pred score of the mutated peptide for MHC-II neoepitopes | MHC-II binding with mixMHC2pred | | MixMHC2pred_rank | MixMHC2pred rank of the mutated peptide for MHC-II neoepitopes | MHC-II binding with mixMHC2pred | -| MixMHC2pred_WT_score | MixMHC2pred score of the wild type peptide for MHC-II neoepitopes | MHC-II binding with mixMHC2pred | +| MixMHC2pred_WT_score | MixMHC2pred score of the wild type peptide for MHC-II neoepitopes | MHC-II binding with mixMHC2pred | | MixMHC2pred_WT_rank | MixMHC2pred rank of the wild type peptide for MHC-II neoepitopes | MHC-II binding with mixMHC2pred | -| PRIME_score | PRIME score of the mutated peptide for MHC-I neoepitopes | MHC-I binding with PRIME | +| PRIME_score | PRIME score of the mutated peptide for MHC-I neoepitopes | MHC-I binding with PRIME | | PRIME_rank | PRIME rank of the mutated peptide for MHC-I neoepitopes | MHC-I binding with PRIME | -| PRIME_WT_score | PRIME score of the wild type peptide for MHC-I neoepitopes | MHC-I binding with PRIME | +| PRIME_WT_score | PRIME score of the wild type peptide for MHC-I neoepitopes | MHC-I binding with PRIME | | PRIME_WT_rank | PRIME rank of the wild type peptide for MHC-I neoepitopes | MHC-I binding with PRIME | | DAI | difference of `affinityWildType` and `affinityMutated` | DAI (only availble for MHC-I) | | IEDB_Immunogenicity | IEDB Immunogenicity score for `affinityMutated` | IEDB immunogenicity | diff --git a/neofox/__init__.py b/neofox/__init__.py index 7a160397..9a147921 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b18" +VERSION = "1.1.0b19" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" diff --git a/neofox/tests/integration_tests/test_neoantigen_fitness.py b/neofox/tests/integration_tests/test_neoantigen_fitness.py index 24d6decb..7a2651e7 100755 --- a/neofox/tests/integration_tests/test_neoantigen_fitness.py +++ b/neofox/tests/integration_tests/test_neoantigen_fitness.py @@ -48,7 +48,7 @@ def test_pathogen_similarity(self): result = self.neoantigen_fitness_calculator.get_pathogen_similarity( peptide="FIAGDAAIV" ) - self.assertEqual(0.9923850668756105, result) + self.assertEqual(0.9961779812291349, result) # tests a non pathogen sequence and expects 0 similarity result = self.neoantigen_fitness_calculator.get_pathogen_similarity( peptide="DDDDDMMDD" diff --git a/neofox/tests/integration_tests/test_neofox.py b/neofox/tests/integration_tests/test_neofox.py index 83ac3088..25807704 100755 --- a/neofox/tests/integration_tests/test_neofox.py +++ b/neofox/tests/integration_tests/test_neofox.py @@ -408,6 +408,19 @@ def test_neoantigens_with_rna_expression(self): for n in neofox.neoantigens: self.assertEqual(n.rna_expression, 1.2) + def test_neoantigens_with_many_rna_expressions(self): + """""" + neoantigens, patients = self._get_test_data() + values = [1.2, 2, 3.1, 0.9, 4] + for n, val in zip(neoantigens, values): + n.rna_expression = val + neofox = NeoFox( + neoantigens=neoantigens, + patients=patients, + num_cpus=4 + ) + for n, val in zip(neofox.neoantigens, values): + self.assertEqual(n.rna_expression, val) def test_patient_with_non_existing_allele_does_not_crash(self): """""" diff --git a/neofox/tests/integration_tests/test_neofox_epitope.py b/neofox/tests/integration_tests/test_neofox_epitope.py index 2316c3d5..059bf670 100755 --- a/neofox/tests/integration_tests/test_neofox_epitope.py +++ b/neofox/tests/integration_tests/test_neofox_epitope.py @@ -286,7 +286,9 @@ def test_with_expression_imputation(self): for n, n2 in zip(neoepitopes, neofox_runner.neoepitopes): self.assertIsNotNone(n2.imputed_gene_expression) self.assertNotEqual(n2.imputed_gene_expression, 0) - self.assertEqual(n2.imputed_gene_expression, n2.rna_expression) + self.assertNotEqual(n2.imputed_gene_expression, n2.rna_expression) + self.assertEqual(n.rna_expression, n2.rna_expression) + self.assertEqual(n.imputed_gene_expression, n2.imputed_gene_expression) def _assert_neeoepitope(self, neoepitope: PredictedEpitope): # netMHCpan or netMHC2pan annotations From 2896a6972dd67b58f21ca387aaab39a7827f74e8 Mon Sep 17 00:00:00 2001 From: "Kress, Luis" Date: Tue, 9 May 2023 09:27:59 +0200 Subject: [PATCH 29/83] Update version --- neofox/__init__.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index 7a160397..9a147921 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b18" +VERSION = "1.1.0b19" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" From 4d6ebe63b3cfbc7ddbdb85468581dd98636d11d2 Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Tue, 9 May 2023 13:25:10 +0200 Subject: [PATCH 30/83] Adapted unit tests to the updates needed for external annotation in epitope mode --- neofox/tests/unit_tests/test_model_converter.py | 4 ++-- 1 file changed, 2 insertions(+), 2 deletions(-) diff --git a/neofox/tests/unit_tests/test_model_converter.py b/neofox/tests/unit_tests/test_model_converter.py index a79446b8..4d30a928 100755 --- a/neofox/tests/unit_tests/test_model_converter.py +++ b/neofox/tests/unit_tests/test_model_converter.py @@ -807,7 +807,7 @@ def test_candidate_neoepitopes2model(self): ) with open(candidate_file) as f: self.count_lines = len(f.readlines()) - neoepitopes = ModelConverter().parse_candidate_neoepitopes_file(candidate_file, self.hla_database) + neoepitopes = ModelConverter().parse_candidate_neoepitopes_file(candidate_file, self.hla_database, ORGANISM_HOMO_SAPIENS) self.assertIsNotNone(neoepitopes) self.assertEqual(self.count_lines -1, len(neoepitopes)) for n in neoepitopes: @@ -821,7 +821,7 @@ def test_candidate_neoepitopes2model_with_patients(self): with open(candidate_file) as f: self.count_lines = len(f.readlines()) - neoepitopes = ModelConverter().parse_candidate_neoepitopes_file(candidate_file, self.hla_database) + neoepitopes = ModelConverter().parse_candidate_neoepitopes_file(candidate_file, self.hla_database, ORGANISM_HOMO_SAPIENS) self.assertIsNotNone(neoepitopes) self.assertEqual(self.count_lines -1, len(neoepitopes)) for n in neoepitopes: From d683892302bd178d88ad5e654030ed30fe41183e Mon Sep 17 00:00:00 2001 From: Franziska Lang Date: Thu, 11 May 2023 08:51:22 +0200 Subject: [PATCH 31/83] remove externalAnnotations column from epitope table in neoantigen mode --- neofox/model/conversion.py | 2 ++ 1 file changed, 2 insertions(+) diff --git a/neofox/model/conversion.py b/neofox/model/conversion.py index 23238bad..c5a4db9b 100755 --- a/neofox/model/conversion.py +++ b/neofox/model/conversion.py @@ -226,6 +226,8 @@ def annotations2epitopes_table(neoantigens: List[Neoantigen], mhc: str) -> pd.Da # concatenates all together epitopes_df = pd.concat(epitopes_dfs) + # has to be dropped otherwise a column containing all external annotations will exist + epitopes_df.drop(["externalAnnotations"], axis=1, inplace=True) epitopes_df.replace('None', NOT_AVAILABLE_VALUE, inplace=True) return epitopes_df From 065f72c5681ef2386cea4bce2bd06a826f0c1b89 Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Fri, 12 May 2023 12:24:41 +0200 Subject: [PATCH 32/83] Adapted IEDB fasta builder to new column names from IEDB. Both header rows are now considered --- neofox/references/installer.py | 29 +++++++++++++++++------------ 1 file changed, 17 insertions(+), 12 deletions(-) diff --git a/neofox/references/installer.py b/neofox/references/installer.py index a41352c1..1dc4cacd 100644 --- a/neofox/references/installer.py +++ b/neofox/references/installer.py @@ -371,20 +371,25 @@ def __init__(self, input_file): self.input_file = input_file def build_fasta(self, organism, process_type, output_file): + # read IEDB header + iedb_head = pd.read_csv(self.input_file, nrows=2, header=None) + # combine the two header rows (table name and value) to get the unique column names + # e.g.: "Epitope:Name", "MHC Restriction:Name", "MHC Restriction:Class", ... + iedb_cols = iedb_head.apply(lambda col: f'{col[0]}:{col[1]}') # read IEDB input file - iedb = pd.read_csv(self.input_file, skiprows=1) + iedb = pd.read_csv(self.input_file, skiprows=2, names=iedb_cols) # filter entries filtered_iedb = iedb[ - (iedb["Name"].str.contains(organism)) - & (iedb["Object Type"] == "Linear peptide") - & (iedb["Process Type"] == process_type) - & (iedb["Qualitative Measure"] == "Positive") - & (iedb["Class"] == "I") + (iedb["Host:Name"].str.contains(organism)) + & (iedb["Epitope:Object Type"] == "Linear peptide") + & (iedb["1st in vivo Process:Process Type"] == process_type) + & (iedb["Assay:Qualitative Measurement"] == "Positive") + & (iedb["MHC Restriction:Class"] == "I") ] # parses peptides and validates them, non-valid peptides are filtered out - filtered_iedb.loc[:, "seq"] = filtered_iedb.loc[:, "Description"].transform( + filtered_iedb.loc[:, "seq"] = filtered_iedb.loc[:, "Epitope:Name"].transform( lambda x: x.strip()) filtered_iedb.loc[:, "valid_peptide"] = filtered_iedb.loc[:, "seq"].transform( lambda x: _verify_alphabet(Seq(x, IUPAC.protein))) @@ -393,17 +398,17 @@ def build_fasta(self, organism, process_type, output_file): # build fasta header: 449|FL-160-2 protein - Trypanosoma cruzi|JH0823|Trypanosoma cruzi|5693 # epitope id|Antigen Name|antigen_id|Organism Name|organism_id filtered_iedb.loc[:, "epitope_id"] = filtered_iedb.loc[ - :, "Epitope IRI" + :, "Epitope:IEDB IRI" ].transform(lambda x: x.replace("http://www.iedb.org/epitope/", "", regex=True)) filtered_iedb.loc[:, "antigen_id"] = filtered_iedb.loc[ - :, "Antigen IRI" + :, "Epitope:Source Molecule IRI" ].transform( lambda x: x.replace( "http://www.ncbi.nlm.nih.gov/protein/", "", regex=True ).replace("https://ontology.iedb.org/ontology/", "", regex=True) ) filtered_iedb.loc[:, "organism_id"] = filtered_iedb.loc[ - :, "Organism IRI" + :, "Epitope:Source Organism IRI" ].transform( lambda x: x.replace( "http://purl.obolibrary.org/obo/NCBITaxon_", "", regex=True @@ -412,9 +417,9 @@ def build_fasta(self, organism, process_type, output_file): filtered_iedb.loc[:, "fasta_header"] = filtered_iedb.apply( lambda row: ">{epitope_id}|{antigen_name}|{antigen_id}|{organism_name}|{organism_id}".format( epitope_id=str(row["epitope_id"]), - antigen_name=row["Antigen Name"], + antigen_name=row["Epitope:Source Molecule"], antigen_id=str(row["antigen_id"]), - organism_name=row["Organism Name"], + organism_name=row["Epitope:Source Organism"], organism_id=str(row["organism_id"]), ), axis=1, From d2593a92ed16d41f04f2123fb12eb2f54d00964c Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Tue, 23 May 2023 18:01:18 +0200 Subject: [PATCH 33/83] Removed unzipping of IEDB file in install script --- neofox/__init__.py | 2 +- neofox/references/installer.py | 11 ++--------- 2 files changed, 3 insertions(+), 10 deletions(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index 9a147921..460b16b6 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b19" +VERSION = "1.1.0b20" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" diff --git a/neofox/references/installer.py b/neofox/references/installer.py index 1dc4cacd..769f0ac3 100644 --- a/neofox/references/installer.py +++ b/neofox/references/installer.py @@ -154,19 +154,12 @@ def _set_iedb(self): os.makedirs(os.path.join(self.reference_folder, IEDB_FOLDER), exist_ok=True) # download IEDB - iedb_zip = os.path.join(self.reference_folder, IEDB_FOLDER, "Iedb.zip") - cmd = 'wget "{}" -O {}'.format(IEDB_URL, iedb_zip) - self._run_command(cmd) - - # unzip IEDB path_to_iedb_folder = os.path.join(self.reference_folder, IEDB_FOLDER) - cmd = "unzip -o {iedb_zip} -d {iedb_folder}".format( - iedb_zip=iedb_zip, iedb_folder=path_to_iedb_folder - ) + tcell_full_iedb_file = os.path.join(path_to_iedb_folder, "tcell_full_v3.zip") + cmd = 'wget "{}" -O {}'.format(IEDB_URL, tcell_full_iedb_file) self._run_command(cmd) # transforms IEDB into fasta - tcell_full_iedb_file = os.path.join(self.reference_folder, IEDB_FOLDER, "tcell_full_v3.csv") hash = self._get_md5_hash(tcell_full_iedb_file) iedb_builder = IedbFastaBuilder(tcell_full_iedb_file) From 0e80a971f25561cede3fb586ad2ec09cc0b4f2b5 Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Thu, 25 May 2023 14:07:58 +0200 Subject: [PATCH 34/83] 286 validate length --- neofox/__init__.py | 2 +- neofox/model/validation.py | 4 ++++ neofox/tests/unit_tests/test_api.py | 16 ---------------- 3 files changed, 5 insertions(+), 17 deletions(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index 460b16b6..0fffdef3 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b20" +VERSION = "1.1.0b21" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" diff --git a/neofox/model/validation.py b/neofox/model/validation.py index a53e16f1..e3c398c3 100755 --- a/neofox/model/validation.py +++ b/neofox/model/validation.py @@ -84,6 +84,8 @@ def validate_neoantigen(neoantigen: Neoantigen): # avoids this validation when there is no wild type if neoantigen.wild_type_xmer: + assert len(neoantigen.wild_type_xmer) == len(neoantigen.mutated_xmer), \ + "Neoantigen does not have the same length of wildtype and mutated sequence." for aa in neoantigen.wild_type_xmer: ModelValidator._validate_aminoacid(aa) @@ -138,6 +140,8 @@ def validate_neoepitope(neoepitope: PredictedEpitope, organism: str): if has_wt_peptide: length_wt_peptide = len(neoepitope.wild_type_peptide) + assert length_wt_peptide == length_mutated_peptide, \ + "Neoepitope does not have the same length of wildtype and mutated sequence." if has_mhc_i: assert ModelValidator.is_mhci_peptide_length_valid(length_wt_peptide), \ "Mutated MHC-I peptide has a non supported length of {}".format(length_wt_peptide) diff --git a/neofox/tests/unit_tests/test_api.py b/neofox/tests/unit_tests/test_api.py index 3a899f0a..d65373c8 100644 --- a/neofox/tests/unit_tests/test_api.py +++ b/neofox/tests/unit_tests/test_api.py @@ -75,19 +75,3 @@ def test_multiple_positions(self): patient_identifier="123") self.assertIsInstance(neoantigen, Neoantigen) self.assertEqual(neoantigen.position, [7, 12]) - - def test_insertion(self): - neoantigen = NeoantigenFactory.build_neoantigen( - mutated_xmer="aaaaaaaaaaaaaaa", - wild_type_xmer="AAAAAAGAAAAgA", - patient_identifier="123") - self.assertIsInstance(neoantigen, Neoantigen) - self.assertEqual(neoantigen.position, [7, 12]) - - def test_deletion(self): - neoantigen = NeoantigenFactory.build_neoantigen( - mutated_xmer="aaaaaaaaaaaaa", - wild_type_xmer="AAAAAAGAAAAgAAA", - patient_identifier="123") - self.assertIsInstance(neoantigen, Neoantigen) - self.assertEqual(neoantigen.position, [7, 12]) From b36b7faa864475aa685f0ec1193cd6ae7edf04cf Mon Sep 17 00:00:00 2001 From: Franziska Lang Date: Thu, 25 May 2023 14:35:23 +0200 Subject: [PATCH 35/83] adjust error message --- neofox/model/validation.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/neofox/model/validation.py b/neofox/model/validation.py index e3c398c3..d9774fac 100755 --- a/neofox/model/validation.py +++ b/neofox/model/validation.py @@ -85,7 +85,7 @@ def validate_neoantigen(neoantigen: Neoantigen): # avoids this validation when there is no wild type if neoantigen.wild_type_xmer: assert len(neoantigen.wild_type_xmer) == len(neoantigen.mutated_xmer), \ - "Neoantigen does not have the same length of wildtype and mutated sequence." + "The length of the wildtype (wildTypeXmer) and mutated peptide sequence (mutatedXmer) are not the same. Both sequences should have the same length in case of point mutations. wildTypeXmer shall be empty, specially in the case of neoantigen candidates derived from other sources than SNVs." for aa in neoantigen.wild_type_xmer: ModelValidator._validate_aminoacid(aa) From f7d60a478cd8699ae6ba5d2ff9b3c8392fbaf631 Mon Sep 17 00:00:00 2001 From: Franziska Lang Date: Thu, 25 May 2023 14:38:47 +0200 Subject: [PATCH 36/83] adjust error message epitope --- neofox/model/validation.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/neofox/model/validation.py b/neofox/model/validation.py index d9774fac..2b1737bf 100755 --- a/neofox/model/validation.py +++ b/neofox/model/validation.py @@ -141,7 +141,7 @@ def validate_neoepitope(neoepitope: PredictedEpitope, organism: str): if has_wt_peptide: length_wt_peptide = len(neoepitope.wild_type_peptide) assert length_wt_peptide == length_mutated_peptide, \ - "Neoepitope does not have the same length of wildtype and mutated sequence." + "Neoepitope does not have the same length of wildtype and mutated sequence. Both sequences should have the same length in case of point mutations. wildTypePeptide shall be empty, specially in the case of neoantigen candidates derived from other sources than SNVs." if has_mhc_i: assert ModelValidator.is_mhci_peptide_length_valid(length_wt_peptide), \ "Mutated MHC-I peptide has a non supported length of {}".format(length_wt_peptide) From df99210c1fe8b4d789378eabecaf503f497fbbab Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Mon, 3 Jul 2023 20:24:22 +0200 Subject: [PATCH 37/83] update PRIME, MixMHC --- .../MHC_predictors/MixMHCpred/mixmhc2pred.py | 22 ++++++++++------ neofox/__init__.py | 2 +- neofox/helpers/intermediate_files.py | 14 ++++++++++ neofox/references/references.py | 5 +++- .../integration_tests/test_mixmhcpred.py | 26 +++++++++---------- neofox/tests/integration_tests/test_prime.py | 8 +++--- 6 files changed, 50 insertions(+), 27 deletions(-) diff --git a/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py b/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py index 8f17985a..29958278 100755 --- a/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py +++ b/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py @@ -58,11 +58,13 @@ def _load_available_alleles(self): loads file with available HLA II alllels for MixMHC2pred prediction, returns set :return: """ + alleles = pd.read_csv( - self.configuration.mix_mhc2_pred_alleles_list, skiprows=1, sep="\t" + self.configuration.mix_mhc2_pred_alleles_list, skiprows=2, sep="\t" ) return list(alleles["AlleleName"]) + @staticmethod def _combine_dq_dp_alleles(alpha_alleles: List[str], beta_alleles: List[str]): """returns patient HLA-DQ/HLA-DP allele combination that are relevant for MixMHC2pred""" @@ -155,37 +157,38 @@ def _parse_mixmhc2pred_output(self, filename: str) -> List[PredictedEpitope]: def _mixmhc2prediction(self, isoforms: List[str], potential_ligand_sequences: List[str]) -> List[PredictedEpitope]: - tmpfasta = intermediate_files.create_temp_fasta(potential_ligand_sequences, prefix="tmp_sequence_") + tmptxt = intermediate_files.create_temp_allele(potential_ligand_sequences, prefix="tmp_sequence_") outtmp = intermediate_files.create_temp_file(prefix="mixmhc2pred", suffix=".txt") cmd = [ self.configuration.mix_mhc2_pred, "-a", " ".join(isoforms), "-i", - tmpfasta, + tmptxt, "-o", outtmp, + "--no_context" ] self.runner.run_command(cmd) results = self._parse_mixmhc2pred_output(filename=outtmp) os.remove(outtmp) - os.remove(tmpfasta) + os.remove(tmptxt) return results def run(self, mhc: List[Mhc2], neoantigen: Neoantigen, uniprot): """ Runs MixMHC2pred: - prediction for peptides of length 13 to 18 based on Suppl Fig. 6 a in Racle, J., et al., Nat. Biotech. (2019). - Robust prediction of HLA class II epitopes by deep motif deconvolution of immunopeptidomes. + prediction for peptides of length 12 to 21 based on Racle, J., et al., Nat. Biotech. (2023). + Machine learning predictions of MHC-II specificities reveal alternative binding mode of class II epitopes. """ # TODO: get rid of this self.results = None potential_ligand_sequences = EpitopeHelper.generate_nmers( - neoantigen=neoantigen, lengths=[13, 14, 15, 16, 17, 18], uniprot=uniprot) + neoantigen=neoantigen, lengths=[12,13, 14, 15, 16, 17, 18,19,20,21], uniprot=uniprot) # filter mps shorter < 13aa filtered_sequences = list( - filter(lambda x: len(x) >= 13, potential_ligand_sequences) + filter(lambda x: len(x) >= 12, potential_ligand_sequences) ) if len(filtered_sequences) > 0: mhc2_alleles = self.transform_hla_ii_alleles_for_prediction(mhc) @@ -194,6 +197,7 @@ def run(self, mhc: List[Mhc2], neoantigen: Neoantigen, uniprot): isoforms=mhc2_alleles, potential_ligand_sequences=filtered_sequences) else: logger.warning("None of the MHC II alleles are supported by MixMHC2pred") + print(mhc2_alleles) def run_peptide(self, peptide: str, isoform: Mhc2Isoform) -> PredictedEpitope: """ @@ -207,6 +211,8 @@ def run_peptide(self, peptide: str, isoform: Mhc2Isoform) -> PredictedEpitope: potential_ligand_sequences=[peptide]) if results: result = results[0] + else: + print('%s is not available in the available alleles.' % isoform_representation) return result def get_annotations(self) -> List[Annotation]: diff --git a/neofox/__init__.py b/neofox/__init__.py index 0fffdef3..5e14e3a8 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b21" +VERSION = "1.1.0b22" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" diff --git a/neofox/helpers/intermediate_files.py b/neofox/helpers/intermediate_files.py index 6908c860..37cdc6b1 100755 --- a/neofox/helpers/intermediate_files.py +++ b/neofox/helpers/intermediate_files.py @@ -52,3 +52,17 @@ def create_temp_peptide(sequences, prefix=None): for seq in sequences: f.write(seq + "\n") return pep_temp_file + +def create_temp_allele(sequences, prefix=None): + """ + Write peptides into a table with two columns: + 1- peptide + 2- context + """ + + # TODO: update the context column soon. + table_temp_file = create_temp_file(prefix=prefix, suffix='.txt') + with open(table_temp_file, "w") as f: + for seq in sequences: + f.write(seq + '\n') + return table_temp_file \ No newline at end of file diff --git a/neofox/references/references.py b/neofox/references/references.py index 94e09e04..90261341 100755 --- a/neofox/references/references.py +++ b/neofox/references/references.py @@ -77,7 +77,7 @@ HLA_DATABASE_AVAILABLE_ALLELES_FILE = "hla_database_allele_list.csv" H2_DATABASE_AVAILABLE_ALLELES_FILE = "h2_database_allele_list.csv" MIXMHCPRED_AVAILABLE_ALLELES_FILE = "allele_list.txt" -MIXMHC2PRED_AVAILABLE_ALLELES_FILE = "Alleles_list.txt" +MIXMHC2PRED_AVAILABLE_ALLELES_FILE = "PWMdef/Alleles_list_Human.txt" PRIME_AVAILABLE_ALLELES_FILE = "alleles.txt" RESOURCES_VERSIONS = "resources_versions.json" @@ -127,13 +127,16 @@ def __init__(self): self.blastp = self._check_and_load_binary(neofox.NEOFOX_BLASTP_ENV, default_value=DEFAULT_BLASTP) self.mix_mhc2_pred = self._check_and_load_binary( neofox.NEOFOX_MIXMHC2PRED_ENV, default_value=DEFAULT_MIXMHC2PRED, optional=True, path_search=False) + if self.mix_mhc2_pred is not None: self.mix_mhc2_pred_alleles_list = os.path.join( os.path.dirname(self.mix_mhc2_pred), MIXMHC2PRED_AVAILABLE_ALLELES_FILE) else: self.mix_mhc2_pred_alleles_list = None + self.mix_mhc_pred = self._check_and_load_binary( neofox.NEOFOX_MIXMHCPRED_ENV, default_value=DEFAULT_MIXMHCPRED, optional=True, path_search=False) + if self.mix_mhc_pred is not None: self.mix_mhc_pred_alleles_list = os.path.join( os.path.dirname(self.mix_mhc_pred), "lib", MIXMHCPRED_AVAILABLE_ALLELES_FILE) diff --git a/neofox/tests/integration_tests/test_mixmhcpred.py b/neofox/tests/integration_tests/test_mixmhcpred.py index ece5f62a..3b147bfb 100755 --- a/neofox/tests/integration_tests/test_mixmhcpred.py +++ b/neofox/tests/integration_tests/test_mixmhcpred.py @@ -54,8 +54,8 @@ def test_mixmhcpred_epitope_iedb(self): best_result = EpitopeHelper.select_best_by_affinity( predictions=self.mixmhcpred.results, maximum=True) self.assertEquals("NLVPMVATV", best_result.mutated_peptide) - self.assertAlmostEqual(0.306957, best_result.affinity_mutated, delta=0.00001) - self.assertEquals(0.6, best_result.rank_mutated) + self.assertAlmostEqual(0.107561, best_result.affinity_mutated, delta=0.00001) + self.assertEquals(0.0659342, best_result.rank_mutated) self.assertEquals("HLA-A*02:01", best_result.allele_mhc_i.name) def test_mixmhcpred_too_small_epitope(self): @@ -81,8 +81,8 @@ def test_mixmhcpred_not_supported_allele(self): best_result = EpitopeHelper.select_best_by_affinity( predictions=self.mixmhcpred.results, maximum=True) self.assertEqual('SIYGGLVLI', best_result.mutated_peptide) - self.assertAlmostEqual(0.158294, best_result.affinity_mutated, places=5) - self.assertEqual(1, best_result.rank_mutated) + self.assertAlmostEqual(-0.296735, best_result.affinity_mutated, places=5) + self.assertEqual(0.267446, best_result.rank_mutated) self.assertEqual('HLA-A*02:01', best_result.allele_mhc_i.name) def test_mixmhcpred_rare_aminoacid(self): @@ -113,9 +113,9 @@ def test_mixmhcpred2_epitope_iedb(self): uniprot=self.uniprot ) best_result = EpitopeHelper.select_best_by_rank(predictions=self.mixmhc2pred.results) - self.assertEquals("DEVLGEPSQDILVT", best_result.mutated_peptide) - self.assertEquals(3.06, best_result.rank_mutated) - self.assertEquals("HLA-DPA1*01:03-DPB1*04:01", best_result.isoform_mhc_i_i.name) + self.assertEquals("TDQTRLEATISPET", best_result.mutated_peptide) + self.assertEquals(0.913, best_result.rank_mutated) + self.assertEquals("HLA-DPA1*01:03-DPB1*13:01", best_result.isoform_mhc_i_i.name) def test_mixmhcpred2_epitope_iedb_forcing_no_drb1(self): # this is an epitope from IEDB of length 15 @@ -128,9 +128,9 @@ def test_mixmhcpred2_epitope_iedb_forcing_no_drb1(self): uniprot=self.uniprot ) best_result = EpitopeHelper.select_best_by_rank(predictions=self.mixmhc2pred.results) - self.assertEquals("DEVLGEPSQDILVT", best_result.mutated_peptide) - self.assertEquals(3.06, best_result.rank_mutated) - self.assertEquals("HLA-DPA1*01:03-DPB1*04:01", best_result.isoform_mhc_i_i.name) + self.assertEquals("TDQTRLEATISPET", best_result.mutated_peptide) + self.assertEquals(0.913, best_result.rank_mutated) + self.assertEquals("HLA-DPA1*01:03-DPB1*13:01", best_result.isoform_mhc_i_i.name) def test_mixmhcpred2_too_small_epitope(self): neoantigen = get_neoantigen(mutated_xmer="ENPVVHFF", wild_type_xmer="ENPVVHFF") @@ -179,9 +179,9 @@ def test_mixmhc2pred_allele(self): logger.info(alleles) self.mixmhc2pred.run(neoantigen=neoantigen, mhc=MHC_TWO_NEW, uniprot=self.uniprot) best_result = EpitopeHelper.select_best_by_rank(predictions=self.mixmhc2pred.results) - self.assertIsNone(best_result.mutated_peptide) - self.assertIsNone(best_result.rank_mutated) - self.assertIsNone(best_result.isoform_mhc_i_i.name) + self.assertIsNotNone(best_result.mutated_peptide) + self.assertIsNotNone(best_result.rank_mutated) + self.assertIsNotNone(best_result.isoform_mhc_i_i.name) def test_generate_nmers(self): neoantigen = get_neoantigen(mutated_xmer="DDDDDVDDD", wild_type_xmer="DDDDDDDDD") diff --git a/neofox/tests/integration_tests/test_prime.py b/neofox/tests/integration_tests/test_prime.py index fdeeb934..fd105575 100755 --- a/neofox/tests/integration_tests/test_prime.py +++ b/neofox/tests/integration_tests/test_prime.py @@ -45,8 +45,8 @@ def test_prime_epitope(self): best_result = EpitopeHelper.select_best_by_affinity( predictions=self.prime.results, maximum=True) self.assertEquals("LVTDQTRL", best_result.mutated_peptide) - self.assertAlmostEqual(0.163810, best_result.affinity_mutated, delta=0.00001) - self.assertEquals(3.00, best_result.rank_mutated) + self.assertAlmostEqual(0.001858 , best_result.affinity_mutated, delta=0.00001) + self.assertEquals(18.992, best_result.rank_mutated) self.assertEquals("HLA-C*05:01", best_result.allele_mhc_i.name) def test_prime_too_small_epitope(self): @@ -72,8 +72,8 @@ def test_prime_not_supported_allele(self): best_result = EpitopeHelper.select_best_by_affinity( predictions=self.prime.results, maximum=True) self.assertEqual('SIYGGLVLI', best_result.mutated_peptide) - self.assertEqual(0.186328, best_result.affinity_mutated) - self.assertEqual(0.2, best_result.rank_mutated) + self.assertEqual(0.13728, best_result.affinity_mutated) + self.assertEqual(0.127, best_result.rank_mutated) self.assertEqual('HLA-A*02:01', best_result.allele_mhc_i.name) def test_prime_rare_aminoacid(self): From 95a71060cc943cd77b1613fb4a39a15e7fdd2ff4 Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Tue, 11 Jul 2023 16:25:07 +0200 Subject: [PATCH 38/83] Added NetMHCIIpan core for bestRank and bestAffinity to output table. Closes #297 --- ...mbine_netmhcIIpan_pred_multiple_binders.py | 8 +++++ .../netmhcpan/netmhcIIpan_prediction.py | 1 + neofox/model/conversion.py | 4 ++- neofox/model/neoantigen.proto | 29 +++++++++++-------- neofox/model/neoantigen.py | 28 ++++++++++-------- 5 files changed, 45 insertions(+), 25 deletions(-) diff --git a/neofox/MHC_predictors/netmhcpan/combine_netmhcIIpan_pred_multiple_binders.py b/neofox/MHC_predictors/netmhcpan/combine_netmhcIIpan_pred_multiple_binders.py index 19913722..cfa31e9e 100755 --- a/neofox/MHC_predictors/netmhcpan/combine_netmhcIIpan_pred_multiple_binders.py +++ b/neofox/MHC_predictors/netmhcpan/combine_netmhcIIpan_pred_multiple_binders.py @@ -199,6 +199,10 @@ def get_annotations(self) -> List[Annotation]: value=self.best_predicted_epitope_rank.isoform_mhc_i_i.name, name="NetMHCIIpan_bestRank_allele", ), + AnnotationFactory.build_annotation( + value=self.best_predicted_epitope_rank.core_mhc_i_i, + name="NetMHCIIpan_bestRank_core", + ), AnnotationFactory.build_annotation( value=self.best_predicted_epitope_rank.rank_wild_type, name="NetMHCIIpan_bestRank_rankWT", @@ -222,6 +226,10 @@ def get_annotations(self) -> List[Annotation]: value=self.best_predicted_epitope_affinity.isoform_mhc_i_i.name, name="NetMHCIIpan_bestAffinity_allele", ), + AnnotationFactory.build_annotation( + value=self.best_predicted_epitope_affinity.core_mhc_i_i, + name="NetMHCIIpan_bestAffinity_core", + ), AnnotationFactory.build_annotation( value=self.best_predicted_epitope_affinity.affinity_wild_type, name="NetMHCIIpan_bestAffinity_affinityWT", diff --git a/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py b/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py index a42933e9..30974752 100755 --- a/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py +++ b/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py @@ -125,6 +125,7 @@ def _parse_netmhcpan_output(self, lines: str) -> List[PredictedEpitope]: PredictedEpitope( position=int(line[0]), isoform_mhc_i_i=self.mhc_parser.parse_mhc2_isoform(line[1]), + core_mhc_i_i=str(line[4]), mutated_peptide=line[2], affinity_mutated=float(line[11]), rank_mutated=float(line[8]), diff --git a/neofox/model/conversion.py b/neofox/model/conversion.py index c5a4db9b..ac1636b3 100755 --- a/neofox/model/conversion.py +++ b/neofox/model/conversion.py @@ -227,7 +227,9 @@ def annotations2epitopes_table(neoantigens: List[Neoantigen], mhc: str) -> pd.Da # concatenates all together epitopes_df = pd.concat(epitopes_dfs) # has to be dropped otherwise a column containing all external annotations will exist - epitopes_df.drop(["externalAnnotations"], axis=1, inplace=True) + # if there are no epitopes below the rank threshold, this column does not exist + if 'externalAnnotations' in epitopes_df.columns: + epitopes_df.drop(["externalAnnotations"], axis=1, inplace=True) epitopes_df.replace('None', NOT_AVAILABLE_VALUE, inplace=True) return epitopes_df diff --git a/neofox/model/neoantigen.proto b/neofox/model/neoantigen.proto index 58c8c12f..272ad117 100755 --- a/neofox/model/neoantigen.proto +++ b/neofox/model/neoantigen.proto @@ -287,58 +287,63 @@ message PredictedEpitope { MHC II isoform */ Mhc2Isoform isoformMhcII = 5; + /** + MHCII core part of the peptide ligand that primarily interacts with the + MHC binding groove, predicted by NetMHCIIpan + */ + string core_mhc_i_i = 6; /** MHC binding affinity for the mutated peptide. This value is estimated with NetMHCpan in case of MHC-I peptides and NetMHCIIpan in cas of MHC-II peptides */ - float affinityMutated = 6; + float affinityMutated = 7; /** MHC binding rank for the mutated peptide. This value is estimated with NetMHCpan in case of MHC-I peptides and NetMHCIIpan in cas of MHC-II peptides */ - float rankMutated = 7; + float rankMutated = 8; /** MHC binding affinity for the wild type peptide. This value is estimated with NetMHCpan in case of MHC-I peptides and NetMHCIIpan in cas of MHC-II peptides */ - float affinityWildType = 8; + float affinityWildType = 9; /** MHC binding rank for the wild type peptide. This value is estimated with NetMHCpan in case of MHC-I peptides and NetMHCIIpan in cas of MHC-II peptides */ - float rankWildType = 9; + float rankWildType = 10; /** The NeoFox neoantigen annotations */ - Annotations neofoxAnnotations = 10; + Annotations neofoxAnnotations = 11; /** Patient identifier */ - string patientIdentifier = 11; + string patientIdentifier = 12; /** The HGNC gene symbol or gene identifier */ - string gene = 12; + string gene = 13; /** Expression value of the transcript from RNA data. Range [0, +inf]. */ - float rnaExpression = 13; + float rnaExpression = 14; /** Expression value of the transcript from TCGA data. Range [0, +inf]. */ - float imputedGeneExpression = 14; + float imputedGeneExpression = 15; /** Variant allele frequency from the DNA. Range [0.0, 1.0] */ - float dnaVariantAlleleFrequency = 15; + float dnaVariantAlleleFrequency = 16; /** Variant allele frequency from the RNA. Range [0.0, 1.0] */ - float rnaVariantAlleleFrequency = 16; + float rnaVariantAlleleFrequency = 17; /** External annotations for neoepitope mode. */ - repeated Annotation externalAnnotations = 17; + repeated Annotation externalAnnotations = 18; } /** diff --git a/neofox/model/neoantigen.py b/neofox/model/neoantigen.py index 579c7301..47e84d83 100755 --- a/neofox/model/neoantigen.py +++ b/neofox/model/neoantigen.py @@ -229,38 +229,42 @@ class PredictedEpitope(betterproto.Message): allele_mhc_i: "MhcAllele" = betterproto.message_field(4) # *MHC II isoform isoform_mhc_i_i: "Mhc2Isoform" = betterproto.message_field(5) + # *MHCII core part of the peptide ligand that primarily interacts with the + # MHC binding groove, predicted by NetMHCIIpan + core_mhc_i_i: str = betterproto.string_field(6) # *MHC binding affinity for the mutated peptide. This value is estimated with # NetMHCpan in case of MHC-I peptidesand NetMHCIIpan in cas of MHC-II # peptides - affinity_mutated: float = betterproto.float_field(6) + affinity_mutated: float = betterproto.float_field(7) # *MHC binding rank for the mutated peptide. This value is estimated with # NetMHCpan in case of MHC-I peptidesand NetMHCIIpan in cas of MHC-II # peptides - rank_mutated: float = betterproto.float_field(7) + rank_mutated: float = betterproto.float_field(8) # *MHC binding affinity for the wild type peptide. This value is estimated # with NetMHCpan in case of MHC-I peptidesand NetMHCIIpan in cas of MHC-II # peptides - affinity_wild_type: float = betterproto.float_field(8) + affinity_wild_type: float = betterproto.float_field(9) # *MHC binding rank for the wild type peptide. This value is estimated with # NetMHCpan in case of MHC-I peptidesand NetMHCIIpan in cas of MHC-II # peptides - rank_wild_type: float = betterproto.float_field(9) + rank_wild_type: float = betterproto.float_field(10) # *The NeoFox neoantigen annotations - neofox_annotations: "Annotations" = betterproto.message_field(10) + neofox_annotations: "Annotations" = betterproto.message_field(11) # *Patient identifier - patient_identifier: str = betterproto.string_field(11) + patient_identifier: str = betterproto.string_field(12) # *The HGNC gene symbol or gene identifier - gene: str = betterproto.string_field(12) + gene: str = betterproto.string_field(13) # *Expression value of the transcript from RNA data. Range [0, +inf]. - rna_expression: float = betterproto.float_field(13) + rna_expression: float = betterproto.float_field(14) # *Expression value of the transcript from TCGA data. Range [0, +inf]. - imputed_gene_expression: float = betterproto.float_field(14) + imputed_gene_expression: float = betterproto.float_field(15) # *Variant allele frequency from the DNA. Range [0.0, 1.0] - dna_variant_allele_frequency: float = betterproto.float_field(15) + dna_variant_allele_frequency: float = betterproto.float_field(16) # *Variant allele frequency from the RNA. Range [0.0, 1.0] - rna_variant_allele_frequency: float = betterproto.float_field(16) + rna_variant_allele_frequency: float = betterproto.float_field(17) # *External annotations for neoepitope mode. - external_annotations: List["Annotation"] = betterproto.message_field(17) + external_annotations: List["Annotation"] = betterproto.message_field(18) + @dataclass class Neoantigen(betterproto.Message): From 9c2855419cd908ffd6fbdf965e7fab851da7aa81 Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Thu, 20 Jul 2023 15:05:25 +0200 Subject: [PATCH 39/83] Cleanup and documentation update. Version increase. --- docs/source/04_developer_guide.md | 2 +- docs/source/05_models.md | 2 ++ neofox/__init__.py | 2 +- neofox/model/Makefile | 4 ++-- neofox/model/conversion.py | 2 ++ neofox/model/models.md | 2 ++ neofox/model/neoantigen.proto | 4 ++-- 7 files changed, 12 insertions(+), 6 deletions(-) diff --git a/docs/source/04_developer_guide.md b/docs/source/04_developer_guide.md index 14e57288..be6ff291 100644 --- a/docs/source/04_developer_guide.md +++ b/docs/source/04_developer_guide.md @@ -61,4 +61,4 @@ The models and the required scripts are in the folder `neofox/models` Build the models into Python code with `make models`. -Build the HTML documentation with `make html`. \ No newline at end of file +Build the HTML documentation with `make html` (this requires membership of the docker group). diff --git a/docs/source/05_models.md b/docs/source/05_models.md index 5d475081..f500aff7 100644 --- a/docs/source/05_models.md +++ b/docs/source/05_models.md @@ -217,6 +217,7 @@ The metadata required for analysis for a given patient + its patient identifier | wildTypePeptide | [string](#string) | | Closest wild type peptide | | alleleMhcI | [MhcAllele](#neoantigen.MhcAllele) | | MHC I allele | | isoformMhcII | [Mhc2Isoform](#neoantigen.Mhc2Isoform) | | MHC II isoform | +| coreMhcII | [string](#string) | | MHCII core part of the peptide ligand that primarily interacts with the MHC binding groove, predicted by NetMHCIIpan | | affinityMutated | [float](#float) | | MHC binding affinity for the mutated peptide. This value is estimated with NetMHCpan in case of MHC-I peptides and NetMHCIIpan in cas of MHC-II peptides | | rankMutated | [float](#float) | | MHC binding rank for the mutated peptide. This value is estimated with NetMHCpan in case of MHC-I peptides and NetMHCIIpan in cas of MHC-II peptides | | affinityWildType | [float](#float) | | MHC binding affinity for the wild type peptide. This value is estimated with NetMHCpan in case of MHC-I peptides and NetMHCIIpan in cas of MHC-II peptides | @@ -228,6 +229,7 @@ The metadata required for analysis for a given patient + its patient identifier | imputedGeneExpression | [float](#float) | | Expression value of the transcript from TCGA data. Range [0, +inf]. | | dnaVariantAlleleFrequency | [float](#float) | | Variant allele frequency from the DNA. Range [0.0, 1.0] | | rnaVariantAlleleFrequency | [float](#float) | | Variant allele frequency from the RNA. Range [0.0, 1.0] | +| externalAnnotations | [Annotation](#neoantigen.Annotation) | repeated | External annotations for neoepitope mode. | diff --git a/neofox/__init__.py b/neofox/__init__.py index 0fffdef3..5e14e3a8 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b21" +VERSION = "1.1.0b22" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" diff --git a/neofox/model/Makefile b/neofox/model/Makefile index 778abef4..d3eda137 100644 --- a/neofox/model/Makefile +++ b/neofox/model/Makefile @@ -2,5 +2,5 @@ models: protoc -I . --python_betterproto_out=. neoantigen.proto html: - sudo docker run --rm -v `pwd`:/out -v `pwd`:/protos pseudomuto/protoc-gen-doc --doc_opt=/protos/models_template.tmpl,models.md - cp models.md ../../docs/source/05_models.md \ No newline at end of file + docker run --rm -v `pwd`:/out -v `pwd`:/protos pseudomuto/protoc-gen-doc --doc_opt=/protos/models_template.tmpl,models.md + cp models.md ../../docs/source/05_models.md diff --git a/neofox/model/conversion.py b/neofox/model/conversion.py index ac1636b3..0eec8eb0 100755 --- a/neofox/model/conversion.py +++ b/neofox/model/conversion.py @@ -200,6 +200,7 @@ def annotations2epitopes_table(neoantigens: List[Neoantigen], mhc: str) -> pd.Da # adapts output table depending on MHC type if mhc == MHC_I: epitopes_temp_df.drop(list(epitopes_temp_df.filter(regex='isoformMhcII.*')), axis=1, inplace=True) + epitopes_temp_df.drop(list(epitopes_temp_df.filter(regex='coreMhcII.*')), axis=1, inplace=True) else: epitopes_temp_df.drop(list(epitopes_temp_df.filter(regex='alleleMhcI.*')), axis=1, inplace=True) @@ -244,6 +245,7 @@ def annotated_neoepitopes2epitopes_table(neoepitopes: List[PredictedEpitope], mh # adapts output table depending on MHC type if mhc == MHC_I: epitopes_df.drop(list(epitopes_df.filter(regex='isoformMhcII.*')), axis=1, inplace=True) + epitopes_df.drop(list(epitopes_df.filter(regex='coreMhcII.*')), axis=1, inplace=True) else: epitopes_df.drop(list(epitopes_df.filter(regex='alleleMhcI.*')), axis=1, inplace=True) diff --git a/neofox/model/models.md b/neofox/model/models.md index 5d475081..f500aff7 100644 --- a/neofox/model/models.md +++ b/neofox/model/models.md @@ -217,6 +217,7 @@ The metadata required for analysis for a given patient + its patient identifier | wildTypePeptide | [string](#string) | | Closest wild type peptide | | alleleMhcI | [MhcAllele](#neoantigen.MhcAllele) | | MHC I allele | | isoformMhcII | [Mhc2Isoform](#neoantigen.Mhc2Isoform) | | MHC II isoform | +| coreMhcII | [string](#string) | | MHCII core part of the peptide ligand that primarily interacts with the MHC binding groove, predicted by NetMHCIIpan | | affinityMutated | [float](#float) | | MHC binding affinity for the mutated peptide. This value is estimated with NetMHCpan in case of MHC-I peptides and NetMHCIIpan in cas of MHC-II peptides | | rankMutated | [float](#float) | | MHC binding rank for the mutated peptide. This value is estimated with NetMHCpan in case of MHC-I peptides and NetMHCIIpan in cas of MHC-II peptides | | affinityWildType | [float](#float) | | MHC binding affinity for the wild type peptide. This value is estimated with NetMHCpan in case of MHC-I peptides and NetMHCIIpan in cas of MHC-II peptides | @@ -228,6 +229,7 @@ The metadata required for analysis for a given patient + its patient identifier | imputedGeneExpression | [float](#float) | | Expression value of the transcript from TCGA data. Range [0, +inf]. | | dnaVariantAlleleFrequency | [float](#float) | | Variant allele frequency from the DNA. Range [0.0, 1.0] | | rnaVariantAlleleFrequency | [float](#float) | | Variant allele frequency from the RNA. Range [0.0, 1.0] | +| externalAnnotations | [Annotation](#neoantigen.Annotation) | repeated | External annotations for neoepitope mode. | diff --git a/neofox/model/neoantigen.proto b/neofox/model/neoantigen.proto index 272ad117..d9670c85 100755 --- a/neofox/model/neoantigen.proto +++ b/neofox/model/neoantigen.proto @@ -289,9 +289,9 @@ message PredictedEpitope { Mhc2Isoform isoformMhcII = 5; /** MHCII core part of the peptide ligand that primarily interacts with the - MHC binding groove, predicted by NetMHCIIpan + MHC binding groove, predicted by NetMHCIIpan */ - string core_mhc_i_i = 6; + string coreMhcII = 6; /** MHC binding affinity for the mutated peptide. This value is estimated with NetMHCpan in case of MHC-I peptides and NetMHCIIpan in cas of MHC-II peptides From c65fca5bcd6b503f78c9aeb81eeb421a7b162585 Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Mon, 31 Jul 2023 19:26:46 +0200 Subject: [PATCH 40/83] Added additional netMHCpan annotations to neoantigen mode --- ...mbine_netmhcIIpan_pred_multiple_binders.py | 18 +++++++++++++-- ...combine_netmhcpan_pred_multiple_binders.py | 22 +++++++++++++++++++ .../netmhcpan/netmhcIIpan_prediction.py | 18 +++++++++++---- .../netmhcpan/netmhcpan_prediction.py | 17 +++++++++++--- neofox/model/neoantigen.proto | 4 ++-- neofox/model/neoantigen.py | 4 ++-- 6 files changed, 70 insertions(+), 13 deletions(-) diff --git a/neofox/MHC_predictors/netmhcpan/combine_netmhcIIpan_pred_multiple_binders.py b/neofox/MHC_predictors/netmhcpan/combine_netmhcIIpan_pred_multiple_binders.py index cfa31e9e..8a077033 100755 --- a/neofox/MHC_predictors/netmhcpan/combine_netmhcIIpan_pred_multiple_binders.py +++ b/neofox/MHC_predictors/netmhcpan/combine_netmhcIIpan_pred_multiple_binders.py @@ -200,7 +200,7 @@ def get_annotations(self) -> List[Annotation]: name="NetMHCIIpan_bestRank_allele", ), AnnotationFactory.build_annotation( - value=self.best_predicted_epitope_rank.core_mhc_i_i, + value=self.best_predicted_epitope_rank.core, name="NetMHCIIpan_bestRank_core", ), AnnotationFactory.build_annotation( @@ -212,6 +212,13 @@ def get_annotations(self) -> List[Annotation]: name="NetMHCIIpan_bestRank_peptideWT", ), ]) + # Additional annotations assigned to the epitopes are added to the output + for annotation in self.best_predicted_epitope_rank.neofox_annotations.annotations: + annotations.append( + AnnotationFactory.build_annotation( + value=annotation.value, name=f"NetMHCIIpan_bestRank_{annotation.name}" + ), + ) if self.best_predicted_epitope_affinity: annotations.extend([ AnnotationFactory.build_annotation( @@ -227,7 +234,7 @@ def get_annotations(self) -> List[Annotation]: name="NetMHCIIpan_bestAffinity_allele", ), AnnotationFactory.build_annotation( - value=self.best_predicted_epitope_affinity.core_mhc_i_i, + value=self.best_predicted_epitope_affinity.core, name="NetMHCIIpan_bestAffinity_core", ), AnnotationFactory.build_annotation( @@ -239,6 +246,13 @@ def get_annotations(self) -> List[Annotation]: name="NetMHCIIpan_bestAffinity_peptideWT", ) ]) + # Additional annotations assigned to the epitopes are added to the output + for annotation in self.best_predicted_epitope_affinity.neofox_annotations.annotations: + annotations.append( + AnnotationFactory.build_annotation( + value=annotation.value, name=f"NetMHCIIpan_bestAffinity_{annotation.name}" + ), + ) if self.organism == ORGANISM_HOMO_SAPIENS: annotations.extend([AnnotationFactory.build_annotation(value=self.phbr_ii, name="PHBR_II")]) diff --git a/neofox/MHC_predictors/netmhcpan/combine_netmhcpan_pred_multiple_binders.py b/neofox/MHC_predictors/netmhcpan/combine_netmhcpan_pred_multiple_binders.py index 3d388757..dd80927a 100755 --- a/neofox/MHC_predictors/netmhcpan/combine_netmhcpan_pred_multiple_binders.py +++ b/neofox/MHC_predictors/netmhcpan/combine_netmhcpan_pred_multiple_binders.py @@ -196,6 +196,10 @@ def get_annotations(self) -> List[Annotation]: value=self.best_epitope_by_rank.mutated_peptide, name="NetMHCpan_bestRank_peptide", ), + AnnotationFactory.build_annotation( + value=self.best_epitope_by_rank.core, + name="NetMHCpan_bestRank_core", + ), AnnotationFactory.build_annotation( value=self.best_epitope_by_rank.allele_mhc_i.name, name="NetMHCpan_bestRank_allele" ), @@ -207,6 +211,13 @@ def get_annotations(self) -> List[Annotation]: name="NetMHCpan_bestRank_peptideWT", ) ]) + # Additional annotations assigned to the epitopes are added to the output + for annotation in self.best_epitope_by_rank.neofox_annotations.annotations: + annotations.append( + AnnotationFactory.build_annotation( + value=annotation.value, name=f"NetMHCpan_bestRank_{annotation.name}" + ), + ) if self.best_epitope_by_affinity: annotations.extend([ AnnotationFactory.build_annotation( @@ -217,6 +228,10 @@ def get_annotations(self) -> List[Annotation]: value=self.best_epitope_by_affinity.mutated_peptide, name="NetMHCpan_bestAffinity_peptide", ), + AnnotationFactory.build_annotation( + value=self.best_epitope_by_affinity.core, + name="NetMHCpan_bestAffinity_core", + ), AnnotationFactory.build_annotation( value=self.best_epitope_by_affinity.allele_mhc_i.name, name="NetMHCpan_bestAffinity_allele", @@ -229,6 +244,13 @@ def get_annotations(self) -> List[Annotation]: value=self.best_epitope_by_affinity.wild_type_peptide, name="NetMHCpan_bestAffinity_peptideWT", )]) + # Additional annotations assigned to the epitopes are added to the output + for annotation in self.best_epitope_by_affinity.neofox_annotations.annotations: + annotations.append( + AnnotationFactory.build_annotation( + value=annotation.value, name=f"NetMHCpan_bestAffinity_{annotation.name}" + ), + ) if self.best_ninemer_epitope_by_rank: annotations.extend([ AnnotationFactory.build_annotation( diff --git a/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py b/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py index 30974752..891063a0 100755 --- a/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py +++ b/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py @@ -26,8 +26,9 @@ from neofox.helpers.epitope_helper import EpitopeHelper from neofox.helpers.runner import Runner from neofox.model.mhc_parser import MhcParser -from neofox.model.neoantigen import Mhc2, Mhc2Name, Mhc2Isoform, PredictedEpitope, Neoantigen +from neofox.model.neoantigen import Mhc2, Mhc2Name, Mhc2Isoform, PredictedEpitope, Neoantigen, Annotation from neofox.references.references import DependenciesConfiguration +from neofox.model.factories import AnnotationFactory class NetMhcIIPanPredictor: @@ -121,18 +122,27 @@ def _parse_netmhcpan_output(self, lines: str) -> List[PredictedEpitope]: continue line = line.split() line = line[0:-1] if len(line) > 12 else line - results.append( - PredictedEpitope( + + pred_epitope = PredictedEpitope( position=int(line[0]), isoform_mhc_i_i=self.mhc_parser.parse_mhc2_isoform(line[1]), - core_mhc_i_i=str(line[4]), + core=str(line[4]), mutated_peptide=line[2], affinity_mutated=float(line[11]), rank_mutated=float(line[8]), ) + pred_epitope.neofox_annotations.annotations.extend( + self.get_additional_netmhcpan_annotations(line) ) + results.append(pred_epitope) return results + def get_additional_netmhcpan_annotations(self, line) -> List[Annotation]: + # additional annotations from netmhcpan + of = AnnotationFactory.build_annotation(name="Of", value=str(line[3])) + core_rel = AnnotationFactory.build_annotation(name="Core_Rel", value=str(line[5])) + return [of, core_rel] + def set_wt_netmhcpan_scores(self, predictions) -> List[PredictedEpitope]: for p in predictions: if p.wild_type_peptide is not None: diff --git a/neofox/MHC_predictors/netmhcpan/netmhcpan_prediction.py b/neofox/MHC_predictors/netmhcpan/netmhcpan_prediction.py index df20503c..12a88b11 100755 --- a/neofox/MHC_predictors/netmhcpan/netmhcpan_prediction.py +++ b/neofox/MHC_predictors/netmhcpan/netmhcpan_prediction.py @@ -26,8 +26,9 @@ from neofox.helpers.epitope_helper import EpitopeHelper from neofox.helpers.runner import Runner from neofox.model.mhc_parser import MhcParser -from neofox.model.neoantigen import Mhc1, PredictedEpitope, Zygosity, Neoantigen +from neofox.model.neoantigen import Mhc1, PredictedEpitope, Zygosity, Neoantigen, Annotation from neofox.references.references import DependenciesConfiguration +from neofox.model.factories import AnnotationFactory PEPTIDE_LENGTHS = ["8", "9", "10", "11", "12", "13", "14"] @@ -105,17 +106,27 @@ def _parse_netmhcpan_output(self, lines: str) -> List[PredictedEpitope]: raise NeofoxCommandException("netmhcpan threw an error: {}".format(line)) line = line.split() line = line[0:-2] if len(line) > 16 else line - results.append( - PredictedEpitope( + pred_epitope = PredictedEpitope( position=int(line[0]), allele_mhc_i=self.mhc_parser.parse_mhc_allele(line[1]), + core=str(line[3]), mutated_peptide=line[2], affinity_mutated=float(line[15]), rank_mutated=float(line[12]), ) + pred_epitope.neofox_annotations.annotations.extend( + self.get_additional_netmhcpan_annotations(line) ) + results.append(pred_epitope) return results + def get_additional_netmhcpan_annotations(self, line) -> List[Annotation]: + # additional annotations from netmhcpan + icore = AnnotationFactory.build_annotation(name="Icore", value=str(line[9])) + gp = AnnotationFactory.build_annotation(name="Gp", value=str(line[5])) + gl = AnnotationFactory.build_annotation(name="Gl", value=str(line[6])) + return [icore, gp, gl] + def get_alleles_netmhcpan_representation(self, mhc: List[Mhc1]) -> List[str]: return list( map( diff --git a/neofox/model/neoantigen.proto b/neofox/model/neoantigen.proto index d9670c85..bd07ea71 100755 --- a/neofox/model/neoantigen.proto +++ b/neofox/model/neoantigen.proto @@ -289,9 +289,9 @@ message PredictedEpitope { Mhc2Isoform isoformMhcII = 5; /** MHCII core part of the peptide ligand that primarily interacts with the - MHC binding groove, predicted by NetMHCIIpan + MHC binding groove, predicted by NetMHCpan/NetMHCIIpan */ - string coreMhcII = 6; + string core = 6; /** MHC binding affinity for the mutated peptide. This value is estimated with NetMHCpan in case of MHC-I peptides and NetMHCIIpan in cas of MHC-II peptides diff --git a/neofox/model/neoantigen.py b/neofox/model/neoantigen.py index 47e84d83..14eb859c 100755 --- a/neofox/model/neoantigen.py +++ b/neofox/model/neoantigen.py @@ -230,8 +230,8 @@ class PredictedEpitope(betterproto.Message): # *MHC II isoform isoform_mhc_i_i: "Mhc2Isoform" = betterproto.message_field(5) # *MHCII core part of the peptide ligand that primarily interacts with the - # MHC binding groove, predicted by NetMHCIIpan - core_mhc_i_i: str = betterproto.string_field(6) + # MHC binding groove, predicted by NetMHCpan/NetMHCIIpan + core: str = betterproto.string_field(6) # *MHC binding affinity for the mutated peptide. 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z-`Ca|@+|TM|5zWR#;|pxW)*M{s72q53t(HZ-Q+aK{*(>!&?oPQNu?tR8B_QprsDI0 z1~Dm8Ry|e`du3hov-*_uIl5cteq+&{K98Ro`#DZUbt&+RIhP@3hr39`fS1>lNB%P>ko<*` zCHjftQT%Vk_+MN%ZDRi4D*yk5|2nO2|C{~0V&zQS6O}-!;!b4aV@XsKV@2BLO$-pD LL+udw7x#Yv(H@(4 diff --git a/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py b/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py index 891063a0..35b94b83 100755 --- a/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py +++ b/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py @@ -138,7 +138,6 @@ def _parse_netmhcpan_output(self, lines: str) -> List[PredictedEpitope]: return results def get_additional_netmhcpan_annotations(self, line) -> List[Annotation]: - # additional annotations from netmhcpan of = AnnotationFactory.build_annotation(name="Of", value=str(line[3])) core_rel = AnnotationFactory.build_annotation(name="Core_Rel", value=str(line[5])) return [of, core_rel] diff --git a/neofox/MHC_predictors/netmhcpan/netmhcpan_prediction.py b/neofox/MHC_predictors/netmhcpan/netmhcpan_prediction.py index 12a88b11..5699ef50 100755 --- a/neofox/MHC_predictors/netmhcpan/netmhcpan_prediction.py +++ b/neofox/MHC_predictors/netmhcpan/netmhcpan_prediction.py @@ -121,10 +121,11 @@ def _parse_netmhcpan_output(self, lines: str) -> List[PredictedEpitope]: return results def get_additional_netmhcpan_annotations(self, line) -> List[Annotation]: - # additional annotations from netmhcpan icore = AnnotationFactory.build_annotation(name="Icore", value=str(line[9])) - gp = AnnotationFactory.build_annotation(name="Gp", value=str(line[5])) - gl = AnnotationFactory.build_annotation(name="Gl", value=str(line[6])) + # Position of the deletion, if any. + gp = AnnotationFactory.build_annotation(name="Gp", value=int(line[5])) + # Length of the deletion, if any. + gl = AnnotationFactory.build_annotation(name="Gl", value=int(line[6])) return [icore, gp, gl] def get_alleles_netmhcpan_representation(self, mhc: List[Mhc1]) -> List[str]: diff --git a/neofox/annotator/neoepitope_mhc_binding_annotator.py b/neofox/annotator/neoepitope_mhc_binding_annotator.py index e5202822..684484ef 100644 --- a/neofox/annotator/neoepitope_mhc_binding_annotator.py +++ b/neofox/annotator/neoepitope_mhc_binding_annotator.py @@ -105,6 +105,8 @@ def _run_netmhcpan(self, neoepitope: PredictedEpitope) -> PredictedEpitope: sequence=neoepitope.mutated_peptide, alleles=netmhcpan_allele) annotated_neoepitope.affinity_mutated = mutated_epitope.affinity_mutated annotated_neoepitope.rank_mutated = mutated_epitope.rank_mutated + annotated_neoepitope.core = mutated_epitope.core + annotated_neoepitope.neofox_annotations = mutated_epitope.neofox_annotations wt_epitope = self.netmhcpan.mhc_prediction_peptide( sequence=neoepitope.wild_type_peptide, alleles=netmhcpan_allele) annotated_neoepitope.affinity_wild_type = wt_epitope.affinity_mutated @@ -121,6 +123,8 @@ def _run_netmhc2pan(self, neoepitope: PredictedEpitope) -> PredictedEpitope: mhc2_isoform=neoepitope.isoform_mhc_i_i) annotated_neoepitope.affinity_mutated = mutated_epitope.affinity_mutated annotated_neoepitope.rank_mutated = mutated_epitope.rank_mutated + annotated_neoepitope.core = mutated_epitope.core + annotated_neoepitope.neofox_annotations = mutated_epitope.neofox_annotations wt_epitope = self.netmhc2pan.mhc2_prediction_peptide( sequence=neoepitope.wild_type_peptide, mhc2_isoform=neoepitope.isoform_mhc_i_i) From 98f9c41b4c76e55f94993ae98653d061c2d7af00 Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Tue, 1 Aug 2023 09:50:11 +0200 Subject: [PATCH 42/83] Updated documentation --- docs/source/04_developer_guide.md | 2 +- docs/source/05_models.md | 2 +- neofox/model/models.md | 2 +- 3 files changed, 3 insertions(+), 3 deletions(-) diff --git a/docs/source/04_developer_guide.md b/docs/source/04_developer_guide.md index be6ff291..baa65671 100644 --- a/docs/source/04_developer_guide.md +++ b/docs/source/04_developer_guide.md @@ -61,4 +61,4 @@ The models and the required scripts are in the folder `neofox/models` Build the models into Python code with `make models`. -Build the HTML documentation with `make html` (this requires membership of the docker group). +Build the HTML documentation with `make html` (this requires docker). diff --git a/docs/source/05_models.md b/docs/source/05_models.md index f500aff7..34bbce26 100644 --- a/docs/source/05_models.md +++ b/docs/source/05_models.md @@ -217,7 +217,7 @@ The metadata required for analysis for a given patient + its patient identifier | wildTypePeptide | [string](#string) | | Closest wild type peptide | | alleleMhcI | [MhcAllele](#neoantigen.MhcAllele) | | MHC I allele | | isoformMhcII | [Mhc2Isoform](#neoantigen.Mhc2Isoform) | | MHC II isoform | -| coreMhcII | [string](#string) | | MHCII core part of the peptide ligand that primarily interacts with the MHC binding groove, predicted by NetMHCIIpan | +| core | [string](#string) | | MHCII core part of the peptide ligand that primarily interacts with the MHC binding groove, predicted by NetMHCpan/NetMHCIIpan | | affinityMutated | [float](#float) | | MHC binding affinity for the mutated peptide. This value is estimated with NetMHCpan in case of MHC-I peptides and NetMHCIIpan in cas of MHC-II peptides | | rankMutated | [float](#float) | | MHC binding rank for the mutated peptide. This value is estimated with NetMHCpan in case of MHC-I peptides and NetMHCIIpan in cas of MHC-II peptides | | affinityWildType | [float](#float) | | MHC binding affinity for the wild type peptide. This value is estimated with NetMHCpan in case of MHC-I peptides and NetMHCIIpan in cas of MHC-II peptides | diff --git a/neofox/model/models.md b/neofox/model/models.md index f500aff7..34bbce26 100644 --- a/neofox/model/models.md +++ b/neofox/model/models.md @@ -217,7 +217,7 @@ The metadata required for analysis for a given patient + its patient identifier | wildTypePeptide | [string](#string) | | Closest wild type peptide | | alleleMhcI | [MhcAllele](#neoantigen.MhcAllele) | | MHC I allele | | isoformMhcII | [Mhc2Isoform](#neoantigen.Mhc2Isoform) | | MHC II isoform | -| coreMhcII | [string](#string) | | MHCII core part of the peptide ligand that primarily interacts with the MHC binding groove, predicted by NetMHCIIpan | +| core | [string](#string) | | MHCII core part of the peptide ligand that primarily interacts with the MHC binding groove, predicted by NetMHCpan/NetMHCIIpan | | affinityMutated | [float](#float) | | MHC binding affinity for the mutated peptide. This value is estimated with NetMHCpan in case of MHC-I peptides and NetMHCIIpan in cas of MHC-II peptides | | rankMutated | [float](#float) | | MHC binding rank for the mutated peptide. This value is estimated with NetMHCpan in case of MHC-I peptides and NetMHCIIpan in cas of MHC-II peptides | | affinityWildType | [float](#float) | | MHC binding affinity for the wild type peptide. This value is estimated with NetMHCpan in case of MHC-I peptides and NetMHCIIpan in cas of MHC-II peptides | From 20b15df64f4ab8d7d36b95dfef2b9421db4c191d Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Fri, 11 Aug 2023 11:46:35 +0200 Subject: [PATCH 43/83] Added documentation for new columns. 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z6%Dr{OK?#8px^?C0WjJBB!7A6VSXQbOZ%VfTLThi#rxk+Nu-nv?f=iiSXdNT|68L7 yv=j&JfA{bR3k!mcg+=;C{~Vd|v- diff --git a/docs/source/03_02_output_data.md b/docs/source/03_02_output_data.md index 8645d740..9214c76a 100755 --- a/docs/source/03_02_output_data.md +++ b/docs/source/03_02_output_data.md @@ -27,9 +27,19 @@ The following table describes each of the annotations in the output: | mutation_not_found_in_proteome | indicates if mutated amino acid sequence was not found in the WT proteome by exact search | Priority score | | NetMHCpan_bestRank_rank | minimal MHC I binding rank score over all neoepitope candidates (8-11mers) and MHC I alleles | MHC I binding with netMHCpan | | NetMHCpan_bestRank_peptide | neoepitope candidate sequence with minimal MHC I binding rank score | MHC I binding with netMHCpan | +| NetMHCpan_bestRank_core | The minimal 9 amino acid binding core directly in contact with the MHC. | MHC I binding with netMHCpan | +| NetMHCpan_bestRank_Icore | Interaction core. This is the sequence of the binding core including eventual insertions of deletions. | MHC I binding with netMHCpan | +| NetMHCpan_bestRank_Of | Starting position offset of the core in the peptide (0 based) | MHC I binding with netMHCpan | +| NetMHCpan_bestRank_Gp | Position of the deletion (0 based), if any, in the Icore compared to the core. | MHC I binding with netMHCpan | +| NetMHCpan_bestRank_Gl | Length of the deletion, if any, in the Icore compared to the core. | MHC I binding with netMHCpan | | NetMHCpan_bestRank_allele | the MHC I allele related to `NetMHCpan_bestRank_peptide` | MHC I binding with netMHCpan | | NetMHCpan_bestAffinity_affinity | minimal MHC I binding affinity over all neoepitope candidates (8-11mers) and MHC I alleles | MHC I binding with netMHCpan | | NetMHCpan_bestAffinity_peptide | neoepitope candidate sequence with minimal MHC I binding affinity | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_core | The minimal 9 amino acid binding core directly in contact with the MHC. | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_Icore | Interaction core. This is the sequence of the binding core including eventual insertions of deletions. | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_Of | Starting position offset of the core in the peptide (0 based) | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_Gp | Position of the deletion (0 based), if any, in the Icore compared to the core. | MHC I binding with netMHCpan | +| NetMHCpan_bestAffinity_Gl | Length of the deletion, if any, in the Icore compared to the core. | MHC I binding with netMHCpan | | NetMHCpan_bestAffinity_allele | the MHC I allele related to `NetMHCpan_bestAffinity_peptide` | MHC I binding with netMHCpan | | NetMHCpan_bestRank9mer_rank | minimal MHC I binding rank score over all neoepitope candidates (9mers only) and MHC I alleles | MHC I binding with netMHCpan | | NetMHCpan_bestRank9mer_peptide | neoepitope candidate sequence (9mer) with minimal MHC I binding rank score | MHC I binding with netMHCpan | @@ -50,9 +60,15 @@ The following table describes each of the annotations in the output: | NetMHCpan_bestAffinity9mer_anchorMutated | mutation in `NetMHCpan_bestRank9mer_peptide` in an anchor position (i.e. position 2 or 9) | anchor/non-anchor | | NetMHCIIpan_bestRank_rank | minimal MHC II binding rank score over all neoepitope candidates (15mers) and all MHC II alleles | MHC II binding with netMHCIIpan | | NetMHCIIpan_bestRank_peptide | neoepitope candidate sequence with minimal MHC II binding rank score | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestRank_core | Binding core register (9mer) | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestRank_Of | Starting position offset of the optimal binding core (starting from 0) | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestRank_coreRel | Reliability of the binding core, expressed as the fraction of networks in the ensemble selecting the optimal core | MHC II binding with netMHCIIpan | | NetMHCIIpan_bestRank_allele | the MHC II isoform related to `NetMHCIIpan_bestRank_peptide` | MHC II binding with netMHCIIpan | | NetMHCIIpan_bestAffinity_affinity | minimal MHC II binding affinity over all neoepitope candidates (15mers) and all MHC II alleles | MHC II binding with netMHCIIpan | | NetMHCIIpan_bestAffinity_peptide | neoepitope candidate sequence with minimal MHC II binding affinity | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestAffinity_core | Binding core register (9mer) | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestAffinity_Of | Starting position offset of the optimal binding core (starting from 0) | MHC II binding with netMHCIIpan | +| NetMHCIIpan_bestAffinity_coreRel | Reliability of the binding core, expressed as the fraction of networks in the ensemble selecting the optimal core | MHC II binding with netMHCIIpan | | NetMHCIIpan_bestAffinity_allele | the MHC II isoform related to `NetMHCIIpan_bestAffinity_peptide` | MHC II binding with netMHCIIpan | | NetMHCIIpan_bestRank_rankWT | minimal MHC II binding rank of `NetMHCIIpan_bestRank_peptideWT` | MHC II binding with netMHCIIpan | | NetMHCIIpan_bestRank_peptideWT | WT epitope sequence (15mer) that corresponds to ` NetMHCIIpan_bestRank_peptide` | MHC II binding with netMHCIIpan | diff --git a/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py b/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py index 35b94b83..c3941477 100755 --- a/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py +++ b/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py @@ -113,6 +113,12 @@ def mhc2_prediction_peptide( os.remove(tmp_peptide) return result + @staticmethod + def get_additional_netmhcpan_annotations(line) -> List[Annotation]: + of = AnnotationFactory.build_annotation(name="Of", value=str(line[3])) + core_rel = AnnotationFactory.build_annotation(name="Core_Rel", value=str(line[5])) + return [of, core_rel] + def _parse_netmhcpan_output(self, lines: str) -> List[PredictedEpitope]: results = [] for line in lines.splitlines(): @@ -137,11 +143,6 @@ def _parse_netmhcpan_output(self, lines: str) -> List[PredictedEpitope]: results.append(pred_epitope) return results - def get_additional_netmhcpan_annotations(self, line) -> List[Annotation]: - of = AnnotationFactory.build_annotation(name="Of", value=str(line[3])) - core_rel = AnnotationFactory.build_annotation(name="Core_Rel", value=str(line[5])) - return [of, core_rel] - def set_wt_netmhcpan_scores(self, predictions) -> List[PredictedEpitope]: for p in predictions: if p.wild_type_peptide is not None: diff --git a/neofox/MHC_predictors/netmhcpan/netmhcpan_prediction.py b/neofox/MHC_predictors/netmhcpan/netmhcpan_prediction.py index 5699ef50..d7934344 100755 --- a/neofox/MHC_predictors/netmhcpan/netmhcpan_prediction.py +++ b/neofox/MHC_predictors/netmhcpan/netmhcpan_prediction.py @@ -93,6 +93,17 @@ def mhc_prediction_peptide(self, alleles, sequence) -> PredictedEpitope: os.remove(input_file) return result + @staticmethod + def get_additional_netmhcpan_annotations(line) -> List[Annotation]: + icore = AnnotationFactory.build_annotation(name="Icore", value=str(line[9])) + # start position of core in the peptide. + of = AnnotationFactory.build_annotation(name="Of", value=int(line[4])) + # Position of the deletion, if any. + gp = AnnotationFactory.build_annotation(name="Gp", value=int(line[5])) + # Length of the deletion, if any. + gl = AnnotationFactory.build_annotation(name="Gl", value=int(line[6])) + return [icore, of, gp, gl] + def _parse_netmhcpan_output(self, lines: str) -> List[PredictedEpitope]: results = [] for line in lines.splitlines(): @@ -120,14 +131,6 @@ def _parse_netmhcpan_output(self, lines: str) -> List[PredictedEpitope]: results.append(pred_epitope) return results - def get_additional_netmhcpan_annotations(self, line) -> List[Annotation]: - icore = AnnotationFactory.build_annotation(name="Icore", value=str(line[9])) - # Position of the deletion, if any. - gp = AnnotationFactory.build_annotation(name="Gp", value=int(line[5])) - # Length of the deletion, if any. - gl = AnnotationFactory.build_annotation(name="Gl", value=int(line[6])) - return [icore, gp, gl] - def get_alleles_netmhcpan_representation(self, mhc: List[Mhc1]) -> List[str]: return list( map( From a244fb9c47af5e709da4769f200653d11c0e5205 Mon Sep 17 00:00:00 2001 From: "Kress, Luis" Date: Fri, 11 Aug 2023 12:01:25 +0200 Subject: [PATCH 44/83] Increase version. --- neofox/__init__.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index 5e14e3a8..a442b120 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b22" +VERSION = "1.1.0b23" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" From 762458322482ef7ef1c4b0443f37bed47aaf6c35 Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Tue, 15 Aug 2023 10:33:01 +0200 Subject: [PATCH 45/83] Updated documentation for neoepitope. Changed image for gitlab CI since the old image was removed from docker-hub. --- .gitlab-ci.yml | 3 +-- docs/source/03_02_output_data.md | 6 ++++++ neofox/__init__.py | 2 +- neofox/model/neoantigen.proto | 2 +- 4 files changed, 9 insertions(+), 4 deletions(-) diff --git a/.gitlab-ci.yml b/.gitlab-ci.yml index 2001a66b..a2e94a0c 100755 --- a/.gitlab-ci.yml +++ b/.gitlab-ci.yml @@ -18,7 +18,7 @@ ## along with this program. If not, see .## # this image contains multiple Python interpreters -image: fkrull/multi-python:bionic +image: python:3.8.14-buster # Change pip's cache directory to be inside the project directory since we can # only cache local items. @@ -27,7 +27,6 @@ variables: # Pip's cache doesn't store the python packages # https://pip.pypa.io/en/stable/reference/pip_install/#caching -# # If you want to also cache the installed packages, you have to install # them in a virtualenv and cache it as well. cache: diff --git a/docs/source/03_02_output_data.md b/docs/source/03_02_output_data.md index 9214c76a..5ec3f023 100755 --- a/docs/source/03_02_output_data.md +++ b/docs/source/03_02_output_data.md @@ -291,6 +291,7 @@ The following table describes each of the annotations in the output: | dnaVariantAlleleFrequency | the variant allele frequency calculated from the DNA | - | | mutatedSequence | the mutated amino acid sequence | - | | wildTypeSequence | the non-mutated amino acid sequence (when not provided in the input this will contain the Blastp closest sequence in the proteome) | - | +| core | | MHC core part of the peptide ligand that primarily interacts with the MHC binding groove | MHC-I / MHC-II binding with netMHCpan / netMHCIIpan | alleleMhcI / isoformMhcII | either the MHC-I allele for MHC-I neoepitopes or the MHC-II isoform for MHC-II neoepitopes | - | | patientIdentifier | the patient identifier (optional) | - | | rnaExpression | the RNA expression. If expression was imputed, this will will be `imputedGeneExpression` | expression | @@ -314,6 +315,11 @@ The following table describes each of the annotations in the output: | PRIME_WT_score | PRIME score of the wild type peptide for MHC-I neoepitopes | MHC-I binding with PRIME | | PRIME_WT_rank | PRIME rank of the wild type peptide for MHC-I neoepitopes | MHC-I binding with PRIME | | DAI | difference of `affinityWildType` and `affinityMutated` | DAI (only availble for MHC-I) | +| Gl | | Length of the deletion (in the core), if any. | MHC-I / MHC-II binding with netMHCpan / netMHCIIpan +| Gp | | Position of the deletion (in the core), if any. | MHC-I / MHC-II binding with netMHCpan / netMHCIIpan +| Icore | | Interaction core. This is the sequence of the binding core including eventual insertions of deletions. | MHC-I / MHC-II binding with netMHCpan / netMHCIIpan +| Of | | The starting position of the Core within the predicted peptide | MHC-I / MHC-II binding with netMHCpan / netMHCIIpan +| Core_Rel | | Reliability of the (MHCII) binding core, expressed as the fraction of networks in the ensemble selecting the optimal core | MHC-I / MHC-II binding with netMHCpan / netMHCIIpan | IEDB_Immunogenicity | IEDB Immunogenicity score for `affinityMutated` | IEDB immunogenicity | | Improved_Binder_MHCI | ratio of `affinityWildType` and `affinityMutated` > 1.2 | self-similarity (only available for MHC-I) | | Priority_score | combinatorial score of several features such as MHC binding, expression and VAF | Priority score | diff --git a/neofox/__init__.py b/neofox/__init__.py index a442b120..ca7bcff5 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b23" +VERSION = "1.1.0b25" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" diff --git a/neofox/model/neoantigen.proto b/neofox/model/neoantigen.proto index bd07ea71..2cdce1cf 100755 --- a/neofox/model/neoantigen.proto +++ b/neofox/model/neoantigen.proto @@ -288,7 +288,7 @@ message PredictedEpitope { */ Mhc2Isoform isoformMhcII = 5; /** - MHCII core part of the peptide ligand that primarily interacts with the + MHC core part of the peptide ligand that primarily interacts with the MHC binding groove, predicted by NetMHCpan/NetMHCIIpan */ string core = 6; From 96feaf54fc615e6bdc6b864edcc0601c64261cde Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Wed, 16 Aug 2023 19:27:54 +0200 Subject: [PATCH 46/83] correct NAs in PRIME and MixMHC --- .../MHC_predictors/MixMHCpred/mixmhcpred.py | 37 ++++++++++++------- neofox/MHC_predictors/prime.py | 32 +++++++++++----- neofox/__init__.py | 2 +- 3 files changed, 47 insertions(+), 24 deletions(-) diff --git a/neofox/MHC_predictors/MixMHCpred/mixmhcpred.py b/neofox/MHC_predictors/MixMHCpred/mixmhcpred.py index 82c06603..ca500e8c 100755 --- a/neofox/MHC_predictors/MixMHCpred/mixmhcpred.py +++ b/neofox/MHC_predictors/MixMHCpred/mixmhcpred.py @@ -32,9 +32,9 @@ from neofox.references.references import DependenciesConfiguration ALLELE = "BestAllele" -RANK = "%Rank_bestAllele" +RANK = "%Rank_" PEPTIDE = "Peptide" -SCORE = "Score_bestAllele" +SCORE = "Score_" class MixMHCpred: @@ -58,7 +58,7 @@ def _load_available_alleles(self): alleles = pd.read_csv( self.configuration.mix_mhc_pred_alleles_list, sep="\t" ) - return list(alleles["Allele"]) + return set(alleles["Allele"]) def _get_mixmhc_allele_representation(self, mhc_alleles: List[MhcAllele]): return list( @@ -79,17 +79,28 @@ def _parse_mixmhcpred_output(self, filename: str) -> List[PredictedEpitope]: logger.error("Results from MixMHCpred are empty, something went wrong") results = pd.DataFrame() + # all alleles + mhc_alleles = set() + for col in results.columns: + # take out alleles and eliminate the column Score_bestAllele out of the set + if col.startswith(SCORE) and not col.endswith('e'): + allele = col.split('_')[-1] + mhc_alleles.add(allele) + for _, row in results.iterrows(): # when MixMHCpred returns no results it provides a row with the peptide and NAs for other fields # pandas reads NAs as float nan. Skip these - if isinstance(row[ALLELE], str): - parsed_results.append( - PredictedEpitope( - allele_mhc_i=self.mhc_parser.parse_mhc_allele(row[ALLELE]), - mutated_peptide=row[PEPTIDE], - affinity_mutated=float(row[SCORE]), - rank_mutated=float(row[RANK]), - )) + for allele in mhc_alleles: + if isinstance(row[PEPTIDE], str): + score_colname =str(SCORE + allele) + rank_colname = str(RANK + allele) + parsed_results.append( + PredictedEpitope( + allele_mhc_i=self.mhc_parser.parse_mhc_allele(allele), + mutated_peptide=row[PEPTIDE], + affinity_mutated=float(row[score_colname]), + rank_mutated=float(row[rank_colname]), + )) return parsed_results def _mixmhcprediction(self, mhc_alleles: List[str], potential_ligand_sequences) -> List[PredictedEpitope]: @@ -125,7 +136,7 @@ def run(self, neoantigen: Neoantigen, mhc: List[Mhc1], uniprot): # TODO: we may want to extend this to 8 to 14 bp (coordinate this with netMHCpan) potential_ligand_sequences = EpitopeHelper.generate_nmers( - neoantigen=neoantigen, lengths=[8, 9, 10, 11], uniprot=uniprot + neoantigen=neoantigen, lengths=[8, 9, 10, 11, 12, 13, 14], uniprot=uniprot ) if len(potential_ligand_sequences) > 0: mhc1_alleles = self._get_mixmhc_allele_representation([a for m in mhc for a in m.alleles]) @@ -138,7 +149,7 @@ def run_peptide(self, peptide: str, allele: MhcAllele) -> PredictedEpitope: """Runs MixMHCpred on a single peptide""" result = None mhc1_alleles = self._get_mixmhc_allele_representation([allele]) - if len(mhc1_alleles) > 0 and 8 <= len(peptide) <= 14: + if len(mhc1_alleles) > 0: results = self._mixmhcprediction(mhc1_alleles, [peptide]) if results: result = results[0] diff --git a/neofox/MHC_predictors/prime.py b/neofox/MHC_predictors/prime.py index 4931925f..7926d6dc 100755 --- a/neofox/MHC_predictors/prime.py +++ b/neofox/MHC_predictors/prime.py @@ -35,9 +35,9 @@ from neofox.references.references import DependenciesConfiguration ALLELE = "BestAllele" -RANK = "%Rank_bestAllele" +RANK = "%Rank_" PEPTIDE = "Peptide" -SCORE = "Score_bestAllele" +SCORE = "Score_" class Prime: @@ -59,7 +59,7 @@ def __init__(self, runner: Runner, configuration: DependenciesConfiguration, mhc def _load_available_alleles(self): """ - loads file with available HLA II alllels for Prime prediction, returns set + loads file with available HLA II alleles for Prime prediction, returns set :return: """ alleles = pd.read_csv( @@ -86,14 +86,26 @@ def _parse_prime_output(self, filename: str) -> List[PredictedEpitope]: logger.error("Results from PRIME are empty, something went wrong") results = pd.DataFrame() + # all alleles + mhc_alleles = set() + for col in results.columns: + # take out alleles and eliminate the column Score_bestAllele out of the set + if col.startswith(SCORE) and not col.endswith('e'): + allele = col.split('_')[-1] + mhc_alleles.add(allele) + for _, row in results.iterrows(): - parsed_results.append( - PredictedEpitope( - allele_mhc_i=self.mhc_parser.parse_mhc_allele(row[ALLELE]), - mutated_peptide=row[PEPTIDE], - affinity_mutated=float(row[SCORE]), - rank_mutated=float(row[RANK]), - )) + for allele in mhc_alleles: + if isinstance(row[PEPTIDE], str): + score = str(SCORE + allele) + rank = str(RANK + allele) + parsed_results.append( + PredictedEpitope( + allele_mhc_i=self.mhc_parser.parse_mhc_allele(allele), + mutated_peptide=row[PEPTIDE], + affinity_mutated=float(row[score]), + rank_mutated=float(row[rank]), + )) return parsed_results def _prime(self, mhc_alleles: List[str], potential_ligand_sequences) -> List[PredictedEpitope]: diff --git a/neofox/__init__.py b/neofox/__init__.py index 5e14e3a8..46c4d1bd 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b22" +VERSION = "1.1.0b26" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" From 4dd6543558e860eedcb0bc779c67068fd204296e Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Thu, 31 Aug 2023 08:18:21 +0200 Subject: [PATCH 47/83] Adapted column numbers in tests. Renamed coreRel column, to be aligned with documentation --- neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py | 2 +- neofox/tests/integration_tests/test_neofox.py | 4 ++-- 2 files changed, 3 insertions(+), 3 deletions(-) diff --git a/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py b/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py index c3941477..97005b7e 100755 --- a/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py +++ b/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py @@ -116,7 +116,7 @@ def mhc2_prediction_peptide( @staticmethod def get_additional_netmhcpan_annotations(line) -> List[Annotation]: of = AnnotationFactory.build_annotation(name="Of", value=str(line[3])) - core_rel = AnnotationFactory.build_annotation(name="Core_Rel", value=str(line[5])) + core_rel = AnnotationFactory.build_annotation(name="CoreRel", value=str(line[5])) return [of, core_rel] def _parse_netmhcpan_output(self, lines: str) -> List[PredictedEpitope]: diff --git a/neofox/tests/integration_tests/test_neofox.py b/neofox/tests/integration_tests/test_neofox.py index 25807704..6ec9dfb7 100755 --- a/neofox/tests/integration_tests/test_neofox.py +++ b/neofox/tests/integration_tests/test_neofox.py @@ -328,7 +328,7 @@ def test_neofox_without_mhc2(self): ).get_annotations() self.assertEqual(5, len(annotations)) self.assertIsInstance(annotations[0], Neoantigen) - self.assertEqual(len(annotations[0].neofox_annotations.annotations), 66) + self.assertEqual(len(annotations[0].neofox_annotations.annotations), 76) def test_neofox_without_mhc1(self): neoantigens, patients = self._get_test_data() @@ -341,7 +341,7 @@ def test_neofox_without_mhc1(self): ).get_annotations() self.assertEqual(5, len(annotations)) self.assertIsInstance(annotations[0], Neoantigen) - self.assertEqual(len(annotations[0].neofox_annotations.annotations), 40) + self.assertEqual(len(annotations[0].neofox_annotations.annotations), 42) def test_gene_expression_imputation(self): neoantigens, patients = self._get_test_data() From 0a828352746fd1804e4940c158b19ef48d4f4439 Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Thu, 31 Aug 2023 13:03:09 +0200 Subject: [PATCH 48/83] update PRIME with corrections --- .../MHC_predictors/MixMHCpred/mixmhc2pred.py | 17 +++++------ .../MHC_predictors/MixMHCpred/mixmhcpred.py | 29 ++++++++++--------- neofox/MHC_predictors/prime.py | 23 ++++++++------- neofox/__init__.py | 2 +- neofox/helpers/intermediate_files.py | 13 +++++++++ neofox/model/mhc_parser.py | 1 - neofox/references/references.py | 1 - .../integration_tests/test_mixmhcpred.py | 4 +++ 8 files changed, 54 insertions(+), 36 deletions(-) diff --git a/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py b/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py index 29958278..896ff6fe 100755 --- a/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py +++ b/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py @@ -29,6 +29,7 @@ from neofox.model.neoantigen import Annotation, Mhc2, Mhc2GeneName, MhcAllele, PredictedEpitope, Mhc2Isoform, \ Neoantigen + from neofox.model.factories import AnnotationFactory from neofox.helpers import intermediate_files import pandas as pd @@ -157,7 +158,8 @@ def _parse_mixmhc2pred_output(self, filename: str) -> List[PredictedEpitope]: def _mixmhc2prediction(self, isoforms: List[str], potential_ligand_sequences: List[str]) -> List[PredictedEpitope]: - tmptxt = intermediate_files.create_temp_allele(potential_ligand_sequences, prefix="tmp_sequence_") + + tmptxt = intermediate_files.create_temp_mixmhc2pred(potential_ligand_sequences, prefix="tmp_sequence_") outtmp = intermediate_files.create_temp_file(prefix="mixmhc2pred", suffix=".txt") cmd = [ self.configuration.mix_mhc2_pred, @@ -185,16 +187,13 @@ def run(self, mhc: List[Mhc2], neoantigen: Neoantigen, uniprot): self.results = None potential_ligand_sequences = EpitopeHelper.generate_nmers( - neoantigen=neoantigen, lengths=[12,13, 14, 15, 16, 17, 18,19,20,21], uniprot=uniprot) - # filter mps shorter < 13aa - filtered_sequences = list( - filter(lambda x: len(x) >= 12, potential_ligand_sequences) - ) - if len(filtered_sequences) > 0: + neoantigen=neoantigen, lengths=[12,13, 14, 15, 16, 17, 18, 19, 20, 21], uniprot=uniprot) + + if len(potential_ligand_sequences) > 0: mhc2_alleles = self.transform_hla_ii_alleles_for_prediction(mhc) if len(mhc2_alleles) > 0: self.results = self._mixmhc2prediction( - isoforms=mhc2_alleles, potential_ligand_sequences=filtered_sequences) + isoforms=mhc2_alleles, potential_ligand_sequences=potential_ligand_sequences) else: logger.warning("None of the MHC II alleles are supported by MixMHC2pred") print(mhc2_alleles) @@ -212,7 +211,7 @@ def run_peptide(self, peptide: str, isoform: Mhc2Isoform) -> PredictedEpitope: if results: result = results[0] else: - print('%s is not available in the available alleles.' % isoform_representation) + logger.warning("%s is not available in the available alleles." % isoform_representation) return result def get_annotations(self) -> List[Annotation]: diff --git a/neofox/MHC_predictors/MixMHCpred/mixmhcpred.py b/neofox/MHC_predictors/MixMHCpred/mixmhcpred.py index ca500e8c..037632a3 100755 --- a/neofox/MHC_predictors/MixMHCpred/mixmhcpred.py +++ b/neofox/MHC_predictors/MixMHCpred/mixmhcpred.py @@ -70,8 +70,16 @@ def _get_mixmhc_allele_representation(self, mhc_alleles: List[MhcAllele]): ) ) - def _parse_mixmhcpred_output(self, filename: str) -> List[PredictedEpitope]: + def _get_mhc_alleles(self, mixmhc_result): + mhc_alleles = set() + for col in mixmhc_result.columns: + # take out alleles and eliminate the column Score_bestAllele out of the set + if col.startswith(SCORE) and not col.endswith('e'): + allele = col.split('_')[-1] + mhc_alleles.add(allele) + return mhc_alleles + def _parse_mixmhcpred_output(self, filename: str) -> List[PredictedEpitope]: parsed_results = [] try: results = pd.read_csv(filename, sep="\t", comment="#") @@ -79,27 +87,21 @@ def _parse_mixmhcpred_output(self, filename: str) -> List[PredictedEpitope]: logger.error("Results from MixMHCpred are empty, something went wrong") results = pd.DataFrame() - # all alleles - mhc_alleles = set() - for col in results.columns: - # take out alleles and eliminate the column Score_bestAllele out of the set - if col.startswith(SCORE) and not col.endswith('e'): - allele = col.split('_')[-1] - mhc_alleles.add(allele) - + mhc_alleles = self._get_mhc_alleles(results) for _, row in results.iterrows(): # when MixMHCpred returns no results it provides a row with the peptide and NAs for other fields # pandas reads NAs as float nan. Skip these for allele in mhc_alleles: if isinstance(row[PEPTIDE], str): - score_colname =str(SCORE + allele) - rank_colname = str(RANK + allele) + score = str(SCORE + allele) + rank = str(RANK + allele) + parsed_results.append( PredictedEpitope( allele_mhc_i=self.mhc_parser.parse_mhc_allele(allele), mutated_peptide=row[PEPTIDE], - affinity_mutated=float(row[score_colname]), - rank_mutated=float(row[rank_colname]), + affinity_mutated=float(row[score]), + rank_mutated=float(row[rank]), )) return parsed_results @@ -134,7 +136,6 @@ def run(self, neoantigen: Neoantigen, mhc: List[Mhc1], uniprot): # TODO: get rid of this self.results = None - # TODO: we may want to extend this to 8 to 14 bp (coordinate this with netMHCpan) potential_ligand_sequences = EpitopeHelper.generate_nmers( neoantigen=neoantigen, lengths=[8, 9, 10, 11, 12, 13, 14], uniprot=uniprot ) diff --git a/neofox/MHC_predictors/prime.py b/neofox/MHC_predictors/prime.py index 7926d6dc..ae97a1d3 100755 --- a/neofox/MHC_predictors/prime.py +++ b/neofox/MHC_predictors/prime.py @@ -76,29 +76,32 @@ def _get_mixmhc_allele_representation(self, mhc_alleles: List[MhcAllele]): mhc_alleles) ) ) + def _get_mhc_alleles(self, prime_result): + mhc_alleles = set() + for col in prime_result.columns: + # take out alleles and eliminate the column Score_bestAllele out of the set + if col.startswith(SCORE) and not col.endswith('e'): + allele = col.split('_')[-1] + mhc_alleles.add(allele) + return mhc_alleles def _parse_prime_output(self, filename: str) -> List[PredictedEpitope]: - parsed_results = [] try: results = pd.read_csv(filename, sep="\t", comment="#") except EmptyDataError: - logger.error("Results from PRIME are empty, something went wrong") + logger.error("Results from MixMHCpred are empty, something went wrong") results = pd.DataFrame() - # all alleles - mhc_alleles = set() - for col in results.columns: - # take out alleles and eliminate the column Score_bestAllele out of the set - if col.startswith(SCORE) and not col.endswith('e'): - allele = col.split('_')[-1] - mhc_alleles.add(allele) - + mhc_alleles = self._get_mhc_alleles(results) for _, row in results.iterrows(): + # when MixMHCpred returns no results it provides a row with the peptide and NAs for other fields + # pandas reads NAs as float nan. Skip these for allele in mhc_alleles: if isinstance(row[PEPTIDE], str): score = str(SCORE + allele) rank = str(RANK + allele) + parsed_results.append( PredictedEpitope( allele_mhc_i=self.mhc_parser.parse_mhc_allele(allele), diff --git a/neofox/__init__.py b/neofox/__init__.py index 46c4d1bd..4b281bfb 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b26" +VERSION = "1.1.0b27" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" diff --git a/neofox/helpers/intermediate_files.py b/neofox/helpers/intermediate_files.py index 37cdc6b1..530464fd 100755 --- a/neofox/helpers/intermediate_files.py +++ b/neofox/helpers/intermediate_files.py @@ -42,6 +42,19 @@ def create_temp_fasta(sequences, prefix=None, comment_prefix="seq"): counter += 1 return fasta_temp_file +def create_temp_mixmhc2pred(sequences, prefix=None): + """ + Write peptides into a table with two columns: + 1- peptide + 2- context + """ + + # TODO: update the context column soon. + table_temp_file = create_temp_file(prefix=prefix, suffix='.txt') + with open(table_temp_file, "w") as f: + for seq in sequences: + f.write(seq + '\n') + return table_temp_file def create_temp_peptide(sequences, prefix=None): """ diff --git a/neofox/model/mhc_parser.py b/neofox/model/mhc_parser.py index b6082516..41f87870 100644 --- a/neofox/model/mhc_parser.py +++ b/neofox/model/mhc_parser.py @@ -80,7 +80,6 @@ def get_mhc_parser(mhc_database: MhcDatabase): raise NeofoxInputParametersException("Organism not supported {}".format(mhc_database.organism)) return mhc_parser - class H2Parser(MhcParser): def parse_mhc_allele(self, allele: str, pattern=H2_ALLELE_PATTERN) -> MhcAllele: diff --git a/neofox/references/references.py b/neofox/references/references.py index 90261341..74b40cf9 100755 --- a/neofox/references/references.py +++ b/neofox/references/references.py @@ -186,7 +186,6 @@ def is_homo_sapiens(self): def is_mus_musculus(self): return self.organism == ORGANISM_MUS_MUSCULUS - class HlaDatabase(MhcDatabase): organism = ORGANISM_HOMO_SAPIENS diff --git a/neofox/tests/integration_tests/test_mixmhcpred.py b/neofox/tests/integration_tests/test_mixmhcpred.py index 3b147bfb..db9a8188 100755 --- a/neofox/tests/integration_tests/test_mixmhcpred.py +++ b/neofox/tests/integration_tests/test_mixmhcpred.py @@ -113,7 +113,11 @@ def test_mixmhcpred2_epitope_iedb(self): uniprot=self.uniprot ) best_result = EpitopeHelper.select_best_by_rank(predictions=self.mixmhc2pred.results) +<<<<<<< Updated upstream self.assertEquals("TDQTRLEATISPET", best_result.mutated_peptide) +======= + self.assertEquals("DEVLGEPSQDILVT", best_result.mutated_peptide) +>>>>>>> Stashed changes self.assertEquals(0.913, best_result.rank_mutated) self.assertEquals("HLA-DPA1*01:03-DPB1*13:01", best_result.isoform_mhc_i_i.name) From 7a2c98cef234dd0859d9c9e24adf1f3d61d6a9db Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Thu, 31 Aug 2023 14:16:35 +0200 Subject: [PATCH 49/83] delete unnecessary code --- neofox/__init__.py | 2 +- neofox/helpers/intermediate_files.py | 16 +--------------- 2 files changed, 2 insertions(+), 16 deletions(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index 4b281bfb..de59c270 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b27" +VERSION = "1.1.0b28" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" diff --git a/neofox/helpers/intermediate_files.py b/neofox/helpers/intermediate_files.py index 530464fd..6b545f7a 100755 --- a/neofox/helpers/intermediate_files.py +++ b/neofox/helpers/intermediate_files.py @@ -64,18 +64,4 @@ def create_temp_peptide(sequences, prefix=None): with open(pep_temp_file, "w") as f: for seq in sequences: f.write(seq + "\n") - return pep_temp_file - -def create_temp_allele(sequences, prefix=None): - """ - Write peptides into a table with two columns: - 1- peptide - 2- context - """ - - # TODO: update the context column soon. - table_temp_file = create_temp_file(prefix=prefix, suffix='.txt') - with open(table_temp_file, "w") as f: - for seq in sequences: - f.write(seq + '\n') - return table_temp_file \ No newline at end of file + return pep_temp_file \ No newline at end of file From 685792f48318e6dcad1dd3cc89472fd1302e741c Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Thu, 31 Aug 2023 14:31:51 +0200 Subject: [PATCH 50/83] solved threads --- neofox/MHC_predictors/MixMHCpred/mixmhcpred.py | 2 +- neofox/model/mhc_parser.py | 1 - 2 files changed, 1 insertion(+), 2 deletions(-) diff --git a/neofox/MHC_predictors/MixMHCpred/mixmhcpred.py b/neofox/MHC_predictors/MixMHCpred/mixmhcpred.py index 037632a3..e72aa830 100755 --- a/neofox/MHC_predictors/MixMHCpred/mixmhcpred.py +++ b/neofox/MHC_predictors/MixMHCpred/mixmhcpred.py @@ -150,7 +150,7 @@ def run_peptide(self, peptide: str, allele: MhcAllele) -> PredictedEpitope: """Runs MixMHCpred on a single peptide""" result = None mhc1_alleles = self._get_mixmhc_allele_representation([allele]) - if len(mhc1_alleles) > 0: + if len(mhc1_alleles) > 0 and 8 <= len(peptide) <= 14: results = self._mixmhcprediction(mhc1_alleles, [peptide]) if results: result = results[0] diff --git a/neofox/model/mhc_parser.py b/neofox/model/mhc_parser.py index 41f87870..10d963a3 100644 --- a/neofox/model/mhc_parser.py +++ b/neofox/model/mhc_parser.py @@ -126,7 +126,6 @@ def get_netmhc2pan_representation(self, isoform: Mhc2Isoform): return "H-2-I{gene}{protein}".format( gene=isoform.alpha_chain.gene.strip("H2"), protein=isoform.alpha_chain.protein) - class HlaParser(MhcParser): def parse_mhc_allele(self, allele: str) -> MhcAllele: From 9f05393a32f798dcf9879aed4e1a0e8169d687dd Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Thu, 31 Aug 2023 14:36:27 +0200 Subject: [PATCH 51/83] add version --- neofox/__init__.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index de59c270..46c4d1bd 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b28" +VERSION = "1.1.0b26" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" From 881bf0c3397597ecb1c99555f137d9b372befdd4 Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Thu, 31 Aug 2023 17:10:16 +0200 Subject: [PATCH 52/83] comment out incorrect lines --- neofox/tests/integration_tests/test_mixmhcpred.py | 4 ---- 1 file changed, 4 deletions(-) diff --git a/neofox/tests/integration_tests/test_mixmhcpred.py b/neofox/tests/integration_tests/test_mixmhcpred.py index db9a8188..3b147bfb 100755 --- a/neofox/tests/integration_tests/test_mixmhcpred.py +++ b/neofox/tests/integration_tests/test_mixmhcpred.py @@ -113,11 +113,7 @@ def test_mixmhcpred2_epitope_iedb(self): uniprot=self.uniprot ) best_result = EpitopeHelper.select_best_by_rank(predictions=self.mixmhc2pred.results) -<<<<<<< Updated upstream self.assertEquals("TDQTRLEATISPET", best_result.mutated_peptide) -======= - self.assertEquals("DEVLGEPSQDILVT", best_result.mutated_peptide) ->>>>>>> Stashed changes self.assertEquals(0.913, best_result.rank_mutated) self.assertEquals("HLA-DPA1*01:03-DPB1*13:01", best_result.isoform_mhc_i_i.name) From c9d48d3c6b5f09258eb6fdec38d5e15b15b5b595 Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Thu, 31 Aug 2023 17:11:16 +0200 Subject: [PATCH 53/83] add new number of version --- neofox/__init__.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index 46c4d1bd..4b281bfb 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b26" +VERSION = "1.1.0b27" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" From 2845b192548d741f0b0a3f186ec110549f0cb942 Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Fri, 1 Sep 2023 16:39:15 +0200 Subject: [PATCH 54/83] Adapted feature name coreRel, to match documentation --- neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py b/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py index 97005b7e..8e7c111e 100755 --- a/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py +++ b/neofox/MHC_predictors/netmhcpan/netmhcIIpan_prediction.py @@ -116,7 +116,7 @@ def mhc2_prediction_peptide( @staticmethod def get_additional_netmhcpan_annotations(line) -> List[Annotation]: of = AnnotationFactory.build_annotation(name="Of", value=str(line[3])) - core_rel = AnnotationFactory.build_annotation(name="CoreRel", value=str(line[5])) + core_rel = AnnotationFactory.build_annotation(name="coreRel", value=str(line[5])) return [of, core_rel] def _parse_netmhcpan_output(self, lines: str) -> List[PredictedEpitope]: From 4b8aedc42051ea3e2fff699f91797b5802c9e328 Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Mon, 4 Sep 2023 08:11:43 +0200 Subject: [PATCH 55/83] Added initialization of NetMHCpan features with None. Adapted true column number in neofox integration test. Version increase. --- ...mbine_netmhcIIpan_pred_multiple_binders.py | 21 +++++++++++++++++++ ...combine_netmhcpan_pred_multiple_binders.py | 20 ++++++++++++++++++ neofox/__init__.py | 2 +- neofox/helpers/epitope_helper.py | 1 + neofox/tests/integration_tests/test_neofox.py | 15 +++++++++++-- 5 files changed, 56 insertions(+), 3 deletions(-) diff --git a/neofox/MHC_predictors/netmhcpan/combine_netmhcIIpan_pred_multiple_binders.py b/neofox/MHC_predictors/netmhcpan/combine_netmhcIIpan_pred_multiple_binders.py index 8a077033..0afc86ce 100755 --- a/neofox/MHC_predictors/netmhcpan/combine_netmhcIIpan_pred_multiple_binders.py +++ b/neofox/MHC_predictors/netmhcpan/combine_netmhcIIpan_pred_multiple_binders.py @@ -46,6 +46,12 @@ def __init__(self, runner: Runner, configuration: DependenciesConfiguration, mhc ) self._initialise() + @staticmethod + def _init_additional_netmhciipan_annotations() -> List[Annotation]: + of = AnnotationFactory.build_annotation(name="Of", value=None) + core_rel = AnnotationFactory.build_annotation(name="coreRel", value=None) + return [of, core_rel] + def _initialise(self): self.phbr_ii = None self.generator_rate = None @@ -53,18 +59,33 @@ def _initialise(self): self.generator_rate_cdn = None self.best_predicted_epitope_rank = PredictedEpitope( mutated_peptide=None, + wild_type_peptide=None, + core=None, position=None, isoform_mhc_i_i=Mhc2Isoform(name=None), affinity_mutated=None, rank_mutated=None, ) + # additional netmhcIIpan annotations are initialized empty to always have + # all output columns in the result table + self.best_predicted_epitope_rank.neofox_annotations.annotations.extend( + self._init_additional_netmhciipan_annotations() + ) + self.best_predicted_epitope_affinity = PredictedEpitope( mutated_peptide=None, + wild_type_peptide=None, + core=None, position=None, isoform_mhc_i_i=Mhc2Isoform(name=None), affinity_mutated=None, rank_mutated=None, ) + # additional netmhcIIpan annotations are initialized empty to always have + # all output columns in the result table + self.best_predicted_epitope_affinity.neofox_annotations.annotations.extend( + self._init_additional_netmhciipan_annotations() + ) self.predictions = [] def calculate_phbr_ii(self, best_epitope_per_allele_mhc2: List[PredictedEpitope]): diff --git a/neofox/MHC_predictors/netmhcpan/combine_netmhcpan_pred_multiple_binders.py b/neofox/MHC_predictors/netmhcpan/combine_netmhcpan_pred_multiple_binders.py index dd80927a..537d35c9 100755 --- a/neofox/MHC_predictors/netmhcpan/combine_netmhcpan_pred_multiple_binders.py +++ b/neofox/MHC_predictors/netmhcpan/combine_netmhcpan_pred_multiple_binders.py @@ -45,6 +45,14 @@ def __init__( blastp_runner=self.blastp_runner ) + @staticmethod + def _init_additional_netmhcpan_annotations() -> List[Annotation]: + icore = AnnotationFactory.build_annotation(name="Icore", value=None) + of = AnnotationFactory.build_annotation(name="Of", value=None) + gp = AnnotationFactory.build_annotation(name="Gp", value=None) + gl = AnnotationFactory.build_annotation(name="Gl", value=None) + return [icore, of, gp, gl] + def _initialise(self): self.phbr_i = None self.generator_rate = None @@ -53,9 +61,21 @@ def _initialise(self): self.generator_rate_adn = None self.generator_rate_cdn = None self.best_epitope_by_rank = EpitopeHelper.get_empty_epitope() + self.best_epitope_by_rank.neofox_annotations.annotations.extend( + self._init_additional_netmhcpan_annotations() + ) self.best_epitope_by_affinity = EpitopeHelper.get_empty_epitope() + self.best_epitope_by_affinity.neofox_annotations.annotations.extend( + self._init_additional_netmhcpan_annotations() + ) self.best_ninemer_epitope_by_affinity = EpitopeHelper.get_empty_epitope() + self.best_ninemer_epitope_by_affinity.neofox_annotations.annotations.extend( + self._init_additional_netmhcpan_annotations() + ) self.best_ninemer_epitope_by_rank = EpitopeHelper.get_empty_epitope() + self.best_ninemer_epitope_by_rank.neofox_annotations.annotations.extend( + self._init_additional_netmhcpan_annotations() + ) self.predictions = [] def calculate_phbr_i( diff --git a/neofox/__init__.py b/neofox/__init__.py index 46c4d1bd..4b281bfb 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b26" +VERSION = "1.1.0b27" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" diff --git a/neofox/helpers/epitope_helper.py b/neofox/helpers/epitope_helper.py index ed38d991..0ce2fea9 100755 --- a/neofox/helpers/epitope_helper.py +++ b/neofox/helpers/epitope_helper.py @@ -147,6 +147,7 @@ def get_empty_epitope(): isoform_mhc_i_i=Mhc2Isoform(name=None), affinity_mutated=None, rank_mutated=None, + core=None, ) @staticmethod diff --git a/neofox/tests/integration_tests/test_neofox.py b/neofox/tests/integration_tests/test_neofox.py index 6ec9dfb7..a95b9b51 100755 --- a/neofox/tests/integration_tests/test_neofox.py +++ b/neofox/tests/integration_tests/test_neofox.py @@ -196,15 +196,20 @@ def test_neofox_only_one_neoantigen(self): def test_neofox_model_input(self): """""" + print("model input") neoantigens, patients = self._get_test_data() annotations = NeoFox( neoantigens=neoantigens, patients=patients, num_cpus=4, ).get_annotations() + print("model input") self.assertEqual(5, len(annotations)) self.assertIsInstance(annotations[0], Neoantigen) - self.assertTrue(len(annotations[0].neofox_annotations.annotations) ==85) + print("model input") + print(annotations[0].neofox_annotations.annotations) + print(len(annotations[0].neofox_annotations.annotations)) + self.assertTrue(len(annotations[0].neofox_annotations.annotations) ==101) def test_neofox_without_mixmhcpreds(self): """ @@ -328,6 +333,9 @@ def test_neofox_without_mhc2(self): ).get_annotations() self.assertEqual(5, len(annotations)) self.assertIsInstance(annotations[0], Neoantigen) + print("without mhcii") + print(annotations[0].neofox_annotations.annotations) + print(len(annotations[0].neofox_annotations.annotations)) self.assertEqual(len(annotations[0].neofox_annotations.annotations), 76) def test_neofox_without_mhc1(self): @@ -341,7 +349,10 @@ def test_neofox_without_mhc1(self): ).get_annotations() self.assertEqual(5, len(annotations)) self.assertIsInstance(annotations[0], Neoantigen) - self.assertEqual(len(annotations[0].neofox_annotations.annotations), 42) + print("without_mhci") + print(annotations[0].neofox_annotations.annotations) + print(len(annotations[0].neofox_annotations.annotations)) + self.assertEqual(len(annotations[0].neofox_annotations.annotations), 46) def test_gene_expression_imputation(self): neoantigens, patients = self._get_test_data() From b1d27e8e0e8b071082744e6dfe6737372619863a Mon Sep 17 00:00:00 2001 From: Franziska Lang Date: Tue, 12 Sep 2023 17:28:20 +0200 Subject: [PATCH 56/83] update doc --- README.md | 22 +++++++++++----------- docs/source/01_overview.md | 6 +++--- docs/source/02_installation.md | 29 +++++++++++++++++------------ 3 files changed, 31 insertions(+), 26 deletions(-) diff --git a/README.md b/README.md index 0d92c909..488752d0 100755 --- a/README.md +++ b/README.md @@ -29,8 +29,8 @@ NeoFox covers the following neoantigen features and prediction algorithms: |---------------------------------------------------------|--------------------------------------------------------------------------|-------------------------------------------------------------------------------------------| | MHC I binding affinity/rank score (netMHCpan-v4.1) | Reynisson et al, 2020, Nucleic Acids Research | https://doi.org/10.4049/jimmunol.1700893 | | MHC II binding affinity/rank score (netMHCIIpan-v4.0) | Reynisson et al, 2020, Nucleic Acids Research | https://doi.org/10.1111/imm.12889 | -| MixMHCpred score v2.1 § | Bassani-Sternberg et al., 2017, PLoS Comp Bio; Gfeller, 2018, J Immunol. | https://doi.org/10.1371/journal.pcbi.1005725 , https://doi.org/10.4049/jimmunol.1800914 | -| MixMHC2pred score v1.2 § | Racle et al, 2019, Nat. Biotech. 2019 | https://doi.org/10.1038/s41587-019-0289-6 | +| MixMHCpred score v2.2 § | Bassani-Sternberg et al., 2017, PLoS Comp Bio; Gfeller, 2018, J Immunol. | https://doi.org/10.1371/journal.pcbi.1005725 , https://doi.org/10.4049/jimmunol.1800914 | +| MixMHC2pred score v2.0.2 § | Racle et al, 2019, Nat. Biotech. 2019 | https://doi.org/10.1038/s41587-019-0289-6 | | Differential Agretopicity Index (DAI) | Duan et al, 2014, JEM; Ghorani et al., 2018, Ann Oncol. | https://doi.org/10.1084/jem.20141308 | | Self-Similarity | Bjerregaard et al, 2017, Front Immunol. | https://doi.org/10.3389/fimmu.2017.01566 | | IEDB immunogenicity | Calis et al, 2013, PLoS Comput Biol. | https://doi.org/10.1371/journal.pcbi.1003266 | @@ -57,9 +57,9 @@ NeoFox depends on the following tools: - BLAST 2.10.1 - netMHCpan 4.1 - netMHCIIpan 4.0 -- MixMHCpred 2.1 -- MixMHC2pred 1.2 -- PRIME 1.0 +- MixMHCpred 2.2 +- MixMHC2pred 2.0.2 +- PRIME 2.0 Install from PyPI: ``` @@ -101,10 +101,10 @@ NEOFOX_RSCRIPT=`which Rscript` NEOFOX_BLASTP=path/to/ncbi-blast-2.10.1+/bin/blastp NEOFOX_NETMHCPAN=path/to/netMHCpan-4.1/netMHCpan NEOFOX_NETMHC2PAN=path/to/netMHCIIpan-4.0/netMHCIIpan -NEOFOX_MIXMHCPRED=path/to/MixMHCpred-2.1/MixMHCpred -NEOFOX_MIXMHC2PRED=path/to/MixMHC2pred-1.2/MixMHC2pred_unix +NEOFOX_MIXMHCPRED=path/to/MixMHCpred-2.2/MixMHCpred +NEOFOX_MIXMHC2PRED=path/to/MixMHC2pred-2.0.1/MixMHC2pred_unix NEOFOX_MAKEBLASTDB=path/to/ncbi-blast-2.8.1+/bin/makeblastdb -NEOFOX_PRIME=/path/to/PRIME/PRIME +NEOFOX_PRIME=/path/to/PRIME-2.0/PRIME ```` ## 4 Input data @@ -112,7 +112,7 @@ NEOFOX_PRIME=/path/to/PRIME/PRIME ### 4.1 Neoantigen candidates in tabular format This is an dummy example of a table with neoantigen candidates: -| gene | mutation.wildTypeXmer | mutation.mutatedXmer | patientIdentifier | rnaExpression | rnaVariantAlleleFrequency | dnaVariantAlleleFrequency | external_annotation_1 | external_annotation_2 | +| gene | wildTypeXmer | mutatedXmer | patientIdentifier | rnaExpression | rnaVariantAlleleFrequency | dnaVariantAlleleFrequency | external_annotation_1 | external_annotation_2 | |-------|-----------------------------|-----------------------------|-------------------|---------------|---------------------------|---------------------------|-----------------------|-----------------------| | BRCA2 | AAAAAAAAAAAAALAAAAAAAAAAAAA | AAAAAAAAAAAAAFAAAAAAAAAAAAA | Ptx | 7.942 | 0.85 | 0.34 | some_value | some_value | | BRCA2 | AAAAAAAAAAAAAMAAAAAAAAAAAAA | AAAAAAAAAAAAARAAAAAAAAAAAAA | Ptx | 7.942 | 0.85 | 0.34 | some_value | some_value | @@ -122,8 +122,8 @@ This is an dummy example of a table with neoantigen candidates: where: - `gene`: the HGNC gene symbol -- `mutation.mutatedXmer`: the neoantigen candidate sequence, i.e. the mutated amino acid sequence. The mutation should be located in the middle, flanked by 13 amino acid on both sites (IUPAC 1 respecting casing, eg: A) -- `mutation.wildTypeXmer`: the equivalent non-mutated amino acid sequence (IUPAC 1 respecting casing, eg: A) +- `mutatedXmer`: the neoantigen candidate sequence, i.e. the mutated amino acid sequence. The mutation should be located in the middle, flanked by 13 amino acid on both sites (IUPAC 1 respecting casing, eg: A) +- `wildTypeXmer`: the equivalent non-mutated amino acid sequence (IUPAC 1 respecting casing, eg: A) - `patientIdentifier`: the patient identifier - `rnaExpression`: RNA expression. (**optional**) (see *NOTE*) This value can be in any format chosen by the user (e.g. TPM, RPKM) but it is recommended to be consistent for data that should be compared. - `rnaVariantAlleleFrequency`: the variant allele frequency calculated from the RNA (**optional**, this will be estimated using the `dnaVariantAlleleFrequency` if not available) diff --git a/docs/source/01_overview.md b/docs/source/01_overview.md index ec3cef1d..a8f57019 100644 --- a/docs/source/01_overview.md +++ b/docs/source/01_overview.md @@ -30,8 +30,8 @@ A list of implemented features and their references are given in Table 1. Please |---------------------------------------------------------|--------------------------------------------------------------------------|-------------------------------------------------------------------------------------------| | MHC I binding affinity/rank score (netMHCpan-v4.1) | Reynisson et al., 2020, Nucleic Acids Res. | https://doi.org/10.1093/nar/gkaa379 | | MHC II binding affinity/rank score (netMHCIIpan-v4.0) | Reynisson et al., 2020, Nucleic Acids Res. | https://doi.org/10.1093/nar/gkaa379 | -| MixMHCpred score v2.1 § | Bassani-Sternberg et al., 2017, PLoS Comp Bio; Gfeller, 2018, J Immunol. | https://doi.org/10.1371/journal.pcbi.1005725 , https://doi.org/10.4049/jimmunol.1800914 | -| MixMHC2pred score v1.2 § | Racle et al., 2019, Nat. Biotech. 2019 | https://doi.org/10.1038/s41587-019-0289-6 | +| MixMHCpred score v2.2 § | Bassani-Sternberg et al., 2017, PLoS Comp Bio; Gfeller, 2018, J Immunol. | https://doi.org/10.1371/journal.pcbi.1005725 , https://doi.org/10.4049/jimmunol.1800914 | +| MixMHC2pred score v2.0.2 § | Racle et al., 2019, Nat. Biotech. 2019 | https://doi.org/10.1038/s41587-019-0289-6 | | Differential Agretopicity Index (DAI) | Duan et al., 2014, JEM; Ghorani et al., 2018, Ann Oncol. | https://doi.org/10.1084/jem.20141308 | | Self-Similarity | Bjerregaard et al., 2017, Front Immunol. | https://doi.org/10.3389/fimmu.2017.01566 | | IEDB immunogenicity | Calis et al., 2013, PLoS Comput Biol. | https://doi.org/10.1371/journal.pcbi.1003266 | @@ -44,7 +44,7 @@ A list of implemented features and their references are given in Table 1. Please | Priority score | Bjerregaard et al., 2017, Cancer Immunol Immunother. | https://doi.org/10.1007/s00262-017-2001-3 | | Tcell predictor | Besser et al., 2019, Journal for ImmunoTherapy of Cancer | https://doi.org/10.1186/s40425-019-0595-z | | neoag | Smith et al., 2019, Cancer Immunology Research | https://doi.org/10.1158/2326-6066.CIR-19-0155 | -| PRIME § | Schmidt et al., 2021, Cell Reports Medicine | https://doi.org/10.1016/j.xcrm.2021.100194 | +| PRIME v2.0 § | Schmidt et al., 2021, Cell Reports Medicine | https://doi.org/10.1016/j.xcrm.2021.100194 | | HEX § | Chiaro et al., 2021, Cancer Immunology Research | https://doi.org/10.1158/2326-6066.CIR-20-0814 | diff --git a/docs/source/02_installation.md b/docs/source/02_installation.md index cf20910c..b63063c5 100755 --- a/docs/source/02_installation.md +++ b/docs/source/02_installation.md @@ -1,7 +1,7 @@ # Installation This guide contains two alternatives to install NeoFox: -- Building a docker image that automates the installation into a container +- Building a docker image that automates the installation into a container (**NOTE**: the docker recipe is not supported in neofox-v1.1.0. Please use an older version ( Date: Thu, 14 Sep 2023 09:42:30 +0200 Subject: [PATCH 57/83] draft of the code - Not merge! --- .../MHC_predictors/MixMHCpred/mixmhc2pred.py | 94 ++++++++++++++----- .../neoantigen_mhc_binding_annotator.py | 25 +++-- neofox/model/mhc_parser.py | 5 +- neofox/references/references.py | 15 ++- 4 files changed, 103 insertions(+), 36 deletions(-) diff --git a/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py b/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py index 896ff6fe..b86a827a 100755 --- a/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py +++ b/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py @@ -23,7 +23,8 @@ from neofox.helpers.epitope_helper import EpitopeHelper from neofox.model.mhc_parser import MhcParser, get_alleles_by_gene -from neofox.references.references import DependenciesConfiguration +from neofox.references.references import DependenciesConfiguration, MhcDatabase, \ + ReferenceFolder, ORGANISM_HOMO_SAPIENS from neofox.helpers.runner import Runner @@ -46,23 +47,31 @@ class MixMHC2pred: ANNOTATION_PREFIX = 'MixMHC2pred' ANNOTATION_PREFIX_WT = 'MixMHC2pred_WT' - def __init__(self, runner: Runner, configuration: DependenciesConfiguration, mhc_parser: MhcParser): + def __init__(self, runner: Runner, configuration: DependenciesConfiguration, mhc_parser: MhcParser, + mhc_database: MhcDatabase): self.runner = runner self.configuration = configuration - self.available_alleles = self._load_available_alleles() + self.mhc_database = mhc_database self.mhc_parser = mhc_parser + self.available_alleles = self._load_available_alleles(mhc_database) + + #self.organism = references.organism self.results = None - def _load_available_alleles(self): + def _load_available_alleles(self, mhc_database): """ loads file with available HLA II alllels for MixMHC2pred prediction, returns set :return: """ - - alleles = pd.read_csv( - self.configuration.mix_mhc2_pred_alleles_list, skiprows=2, sep="\t" - ) + if mhc_database.is_homo_sapiens(): + alleles = pd.read_csv( + self.configuration.mix_mhc2_pred_human_alleles_list, skiprows=2, sep="\t" + ) + else: + alleles = pd.read_csv( + self.configuration.mix_mhc2_pred_mouse_alleles_list, skiprows=2, sep="\t" + ) return list(alleles["AlleleName"]) @@ -87,7 +96,8 @@ def _combine_dq_dp_alleles(alpha_alleles: List[str], beta_alleles: List[str]): return alleles_pairs + alleles_triplets @staticmethod - def _get_mixmhc2_allele_representation(hla_alleles: List[MhcAllele]): + def _get_mixmhc2_allele_human_representation(hla_alleles: List[MhcAllele]): + # alleles: hla_alleles return list( map( lambda x: "{gene}_{group}_{protein}".format( @@ -98,12 +108,12 @@ def _get_mixmhc2_allele_representation(hla_alleles: List[MhcAllele]): ) @staticmethod - def _get_mixmhc2_isoform_representation(isoform: Mhc2Isoform): + def _get_mixmhc2_isoform_human_representation(isoform: Mhc2Isoform): - beta_chain = MixMHC2pred._get_mixmhc2_allele_representation([isoform.beta_chain])[0] + beta_chain = MixMHC2pred._get_mixmhc2_allele_human_representation([isoform.beta_chain])[0] if isoform.alpha_chain is not None and isoform.alpha_chain.name: # for DR only beta chain is provided - alpha_chain = MixMHC2pred._get_mixmhc2_allele_representation([isoform.alpha_chain])[0] + alpha_chain = MixMHC2pred._get_mixmhc2_allele_human_representation([isoform.alpha_chain])[0] return "{alpha}__{beta}".format(alpha=alpha_chain, beta=beta_chain) return beta_chain @@ -118,22 +128,51 @@ def transform_hla_ii_alleles_for_prediction(self, mhc: List[Mhc2]) -> List[str]: dqb1_alleles = get_alleles_by_gene(mhc, Mhc2GeneName.DQB1) dp_allele_combinations = self._combine_dq_dp_alleles( - alpha_alleles=self._get_mixmhc2_allele_representation(dpa1_alleles), - beta_alleles=self._get_mixmhc2_allele_representation(dpb1_alleles) + alpha_alleles=self._get_mixmhc2_allele_human_representation(dpa1_alleles), + beta_alleles=self._get_mixmhc2_allele_human_representation(dpb1_alleles) ) dq_allele_combinations = self._combine_dq_dp_alleles( - alpha_alleles=self._get_mixmhc2_allele_representation(dqa1_alleles), - beta_alleles=self._get_mixmhc2_allele_representation(dqb1_alleles) + alpha_alleles=self._get_mixmhc2_allele_human_representation(dqa1_alleles), + beta_alleles=self._get_mixmhc2_allele_human_representation(dqb1_alleles) ) return [ a - for a in self._get_mixmhc2_allele_representation(drb1_alleles) + for a in self._get_mixmhc2_allele_human_representation(drb1_alleles) + dq_allele_combinations + dp_allele_combinations if a in self.available_alleles ] + @staticmethod + def _get_mixmhc2_allele_mouse_representation(h2_alleles: List[MhcAllele]): + return list( + map( + lambda x: "{gene}_{protein}".format( + gene=x.gene[-1], protein=x.protein + ), + h2_alleles, + ) + ) + + def _get_mixmhc2_isoform_mouse_representation(isoform: Mhc2Isoform): + if isoform is not None: + return "H2_{gene}a_{protein}__H2_{gene}b_{protein}".format( + gene=isoform[-3], protein=isoform[-1] + ) + + def transform_h2_alleles_for_prediction(self, mhc:List[Mhc2]) -> List[str]: + """ + prepares list of H2 alleles for prediction in required format + """ + + h2a_alleles = get_alleles_by_gene(mhc, Mhc2GeneName.H2A) + h2e_alleles = get_alleles_by_gene(mhc, Mhc2GeneName.H2E) + + return [ + a for i in (h2a_alleles, h2e_alleles) for a in self._get_mixmhc2_allele_mouse_representation(i) if a in self.available_alleles + ] + def _parse_mixmhc2pred_output(self, filename: str) -> List[PredictedEpitope]: parsed_results = [] @@ -158,9 +197,13 @@ def _parse_mixmhc2pred_output(self, filename: str) -> List[PredictedEpitope]: def _mixmhc2prediction(self, isoforms: List[str], potential_ligand_sequences: List[str]) -> List[PredictedEpitope]: - tmptxt = intermediate_files.create_temp_mixmhc2pred(potential_ligand_sequences, prefix="tmp_sequence_") outtmp = intermediate_files.create_temp_file(prefix="mixmhc2pred", suffix=".txt") + + if self.mhc_database.is_homo_sapiens(): + pwm_file = '/home/nguyenhv/code/MixMHC2pred/2.0/PWMdef/PWMdef_Human/' + else: + pwm_file = '/home/nguyenhv/code/MixMHC2pred/2.0/PWMdef/PWMdef_Mouse/' cmd = [ self.configuration.mix_mhc2_pred, "-a", @@ -169,6 +212,8 @@ def _mixmhc2prediction(self, isoforms: List[str], potential_ligand_sequences: Li tmptxt, "-o", outtmp, + "-f", #add the full path of the folder + pwm_file, "--no_context" ] self.runner.run_command(cmd) @@ -187,10 +232,14 @@ def run(self, mhc: List[Mhc2], neoantigen: Neoantigen, uniprot): self.results = None potential_ligand_sequences = EpitopeHelper.generate_nmers( - neoantigen=neoantigen, lengths=[12,13, 14, 15, 16, 17, 18, 19, 20, 21], uniprot=uniprot) + neoantigen=neoantigen, lengths=[12, 13, 14, 15, 16, 17, 18, 19, 20, 21], uniprot=uniprot) if len(potential_ligand_sequences) > 0: - mhc2_alleles = self.transform_hla_ii_alleles_for_prediction(mhc) + if self.mhc_database.is_homo_sapiens(): + mhc2_alleles = self.transform_hla_ii_alleles_for_prediction(mhc) + else: + mhc2_alleles = self.transform_h2_alleles_for_prediction(mhc) + if len(mhc2_alleles) > 0: self.results = self._mixmhc2prediction( isoforms=mhc2_alleles, potential_ligand_sequences=potential_ligand_sequences) @@ -203,7 +252,10 @@ def run_peptide(self, peptide: str, isoform: Mhc2Isoform) -> PredictedEpitope: Performs MixMHC2pred prediction for desired hla allele and writes result to temporary file. """ result = None - isoform_representation = self._get_mixmhc2_isoform_representation(isoform) + if self.mhc_database.is_homo_sapiens(): + isoform_representation = self._get_mixmhc2_isoform_human_representation(isoform) + else: + isoform_representation = self._get_mixmhc2_isoform_mouse_representation(isoform) if isoform_representation in self.available_alleles: results = self._mixmhc2prediction( isoforms=[isoform_representation], diff --git a/neofox/annotator/neoantigen_mhc_binding_annotator.py b/neofox/annotator/neoantigen_mhc_binding_annotator.py index 327bf382..b2707e4e 100644 --- a/neofox/annotator/neoantigen_mhc_binding_annotator.py +++ b/neofox/annotator/neoantigen_mhc_binding_annotator.py @@ -8,7 +8,7 @@ from neofox.helpers.runner import Runner from neofox.model.mhc_parser import MhcParser from neofox.model.neoantigen import Neoantigen, Patient -from neofox.references.references import DependenciesConfiguration, AvailableAlleles, ReferenceFolder, \ +from neofox.references.references import DependenciesConfiguration, AvailableAlleles, ReferenceFolder, MhcDatabase, \ ORGANISM_HOMO_SAPIENS @@ -56,16 +56,20 @@ def get_mhc_binding_annotations(self, neoantigen: Neoantigen, patient: Patient): neoantigen, patient ) + + if self.configuration.mix_mhc2_pred is not None and has_mhc2: + mixmhc2pred = self._run_mixmhc2pred( + self.runner, + self.configuration, + self.mhc_parser, + neoantigen, + patient, + self.mhc_database + ) + # avoids running MixMHCpred and PRIME for non human organisms if self.organism == ORGANISM_HOMO_SAPIENS: - if self.configuration.mix_mhc2_pred is not None and has_mhc2: - mixmhc2pred = self._run_mixmhc2pred( - self.runner, - self.configuration, - self.mhc_parser, - neoantigen, - patient, - ) + if self.configuration.mix_mhc_pred is not None and has_mhc1: mixmhcpred = self._run_mixmhcpred( self.runner, @@ -155,7 +159,8 @@ def _run_mixmhc2pred( mhc_parser: MhcParser, neoantigen: Neoantigen, patient: Patient, + mhc_database: MhcDatabase ): - mixmhc2 = MixMHC2pred(runner, configuration, mhc_parser) + mixmhc2 = MixMHC2pred(runner, configuration, mhc_parser, mhc_database) mixmhc2.run(mhc=patient.mhc2, neoantigen=neoantigen, uniprot=self.uniprot) return mixmhc2 \ No newline at end of file diff --git a/neofox/model/mhc_parser.py b/neofox/model/mhc_parser.py index 10d963a3..3d02f98c 100644 --- a/neofox/model/mhc_parser.py +++ b/neofox/model/mhc_parser.py @@ -41,7 +41,7 @@ H2_ALLELE_PATTERN = re.compile(r"(H2-?[KDLAE])([a-z][0-9]?)") H2_NETMHCPAN_ALLELE_PATTERN = re.compile(r"H-2-I?(K|D|L|A|E)([a-z][0-9]?)") H2_MOLECULE_PATTERN = re.compile(r"(H2A|H2E)([a-z][0-9]?)") - +H2_ ALLELE_PATTERN_BY_ORGANISM = { ORGANISM_HOMO_SAPIENS: HLA_ALLELE_PATTERN, ORGANISM_MUS_MUSCULUS: H2_ALLELE_PATTERN, @@ -112,6 +112,9 @@ def parse_mhc_allele(self, allele: str, pattern=H2_ALLELE_PATTERN) -> MhcAllele: def parse_mhc2_isoform(self, allele: str) -> Mhc2Isoform: # MHC II molecules in H2 lab mouse are represented as single chain proteins # NOTE: by convention we represent this allele in both the alpha and beta chains + # format from current version of MixMHC2pred: H2_Aa_b__H2_Aa_b + # "H2_{gene}a_{protein}__H2_{gene}b_{protein}" + match = H2_NETMHCPAN_ALLELE_PATTERN.match(allele) if match: # this ensures that netmhcpan output is normalized diff --git a/neofox/references/references.py b/neofox/references/references.py index 74b40cf9..6261dd21 100755 --- a/neofox/references/references.py +++ b/neofox/references/references.py @@ -77,7 +77,10 @@ HLA_DATABASE_AVAILABLE_ALLELES_FILE = "hla_database_allele_list.csv" H2_DATABASE_AVAILABLE_ALLELES_FILE = "h2_database_allele_list.csv" MIXMHCPRED_AVAILABLE_ALLELES_FILE = "allele_list.txt" -MIXMHC2PRED_AVAILABLE_ALLELES_FILE = "PWMdef/Alleles_list_Human.txt" +MIXMHC2PRED_AVAILABLE_HUMAN_ALLELES_FILE = "PWMdef/PWMdef_total/Alleles_list_Human.txt" +MIXMHC2PRED_AVAILABLE_MOUSE_ALLELES_FILE = "PWMdef/PWMdef_total/Alleles_list_Mouse.txt" + + PRIME_AVAILABLE_ALLELES_FILE = "alleles.txt" RESOURCES_VERSIONS = "resources_versions.json" @@ -129,10 +132,14 @@ def __init__(self): neofox.NEOFOX_MIXMHC2PRED_ENV, default_value=DEFAULT_MIXMHC2PRED, optional=True, path_search=False) if self.mix_mhc2_pred is not None: - self.mix_mhc2_pred_alleles_list = os.path.join( - os.path.dirname(self.mix_mhc2_pred), MIXMHC2PRED_AVAILABLE_ALLELES_FILE) + self.mix_mhc2_pred_human_alleles_list = os.path.join( + os.path.dirname(self.mix_mhc2_pred), MIXMHC2PRED_AVAILABLE_HUMAN_ALLELES_FILE) + self.mix_mhc2_pred_mouse_alleles_list = os.path.join( + os.path.dirname(self.mix_mhc2_pred), MIXMHC2PRED_AVAILABLE_MOUSE_ALLELES_FILE + ) else: - self.mix_mhc2_pred_alleles_list = None + self.mix_mhc2_pred_human_alleles_list = None + self.mix_mhc2_pred_mouse_alleles_list = None self.mix_mhc_pred = self._check_and_load_binary( neofox.NEOFOX_MIXMHCPRED_ENV, default_value=DEFAULT_MIXMHCPRED, optional=True, path_search=False) From 783ed4dffb8094cd29e09bca85670526787638a0 Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Thu, 14 Sep 2023 13:30:48 +0200 Subject: [PATCH 58/83] fixing errors from parsing MixMHC2 allele --- neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py | 14 ++++++-------- neofox/__init__.py | 2 +- neofox/model/mhc_parser.py | 7 ++++++- 3 files changed, 13 insertions(+), 10 deletions(-) diff --git a/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py b/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py index b86a827a..bb1c766a 100755 --- a/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py +++ b/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py @@ -148,7 +148,7 @@ def transform_hla_ii_alleles_for_prediction(self, mhc: List[Mhc2]) -> List[str]: def _get_mixmhc2_allele_mouse_representation(h2_alleles: List[MhcAllele]): return list( map( - lambda x: "{gene}_{protein}".format( + lambda x: "H2_{gene}a_{protein}__H2_{gene}b_{protein}".format( gene=x.gene[-1], protein=x.protein ), h2_alleles, @@ -157,9 +157,7 @@ def _get_mixmhc2_allele_mouse_representation(h2_alleles: List[MhcAllele]): def _get_mixmhc2_isoform_mouse_representation(isoform: Mhc2Isoform): if isoform is not None: - return "H2_{gene}a_{protein}__H2_{gene}b_{protein}".format( - gene=isoform[-3], protein=isoform[-1] - ) + return "H2_{gene}a_{protein}__H2_{gene}b_{protein}".format(gene=isoform[-3], protein=isoform[-1]) def transform_h2_alleles_for_prediction(self, mhc:List[Mhc2]) -> List[str]: """ @@ -196,14 +194,14 @@ def _parse_mixmhc2pred_output(self, filename: str) -> List[PredictedEpitope]: return parsed_results def _mixmhc2prediction(self, isoforms: List[str], potential_ligand_sequences: List[str]) -> List[PredictedEpitope]: - + # TODO: define the pwm_path again because the mouse path is only defined by the config tmptxt = intermediate_files.create_temp_mixmhc2pred(potential_ligand_sequences, prefix="tmp_sequence_") outtmp = intermediate_files.create_temp_file(prefix="mixmhc2pred", suffix=".txt") if self.mhc_database.is_homo_sapiens(): - pwm_file = '/home/nguyenhv/code/MixMHC2pred/2.0/PWMdef/PWMdef_Human/' + pwm_path = '/home/nguyenhv/code/MixMHC2pred/2.0/PWMdef/PWMdef_Human/' else: - pwm_file = '/home/nguyenhv/code/MixMHC2pred/2.0/PWMdef/PWMdef_Mouse/' + pwm_path = '/home/nguyenhv/code/MixMHC2pred/2.0/PWMdef/PWMdef_Mouse/' cmd = [ self.configuration.mix_mhc2_pred, "-a", @@ -213,7 +211,7 @@ def _mixmhc2prediction(self, isoforms: List[str], potential_ligand_sequences: Li "-o", outtmp, "-f", #add the full path of the folder - pwm_file, + pwm_path, "--no_context" ] self.runner.run_command(cmd) diff --git a/neofox/__init__.py b/neofox/__init__.py index 4b281bfb..de59c270 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b27" +VERSION = "1.1.0b28" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" diff --git a/neofox/model/mhc_parser.py b/neofox/model/mhc_parser.py index 3d02f98c..056cedb6 100644 --- a/neofox/model/mhc_parser.py +++ b/neofox/model/mhc_parser.py @@ -41,7 +41,7 @@ H2_ALLELE_PATTERN = re.compile(r"(H2-?[KDLAE])([a-z][0-9]?)") H2_NETMHCPAN_ALLELE_PATTERN = re.compile(r"H-2-I?(K|D|L|A|E)([a-z][0-9]?)") H2_MOLECULE_PATTERN = re.compile(r"(H2A|H2E)([a-z][0-9]?)") -H2_ +H2_MIXMHC2PRED_ALLELE = re.compile(r"H2_(A|E)a_([a-z][0-9]?)__H2_(A|E)b_([a-z][0-9]?)") ALLELE_PATTERN_BY_ORGANISM = { ORGANISM_HOMO_SAPIENS: HLA_ALLELE_PATTERN, ORGANISM_MUS_MUSCULUS: H2_ALLELE_PATTERN, @@ -116,6 +116,11 @@ def parse_mhc2_isoform(self, allele: str) -> Mhc2Isoform: # "H2_{gene}a_{protein}__H2_{gene}b_{protein}" match = H2_NETMHCPAN_ALLELE_PATTERN.match(allele) + + # convert the allele format in MixMHC2pred to the normal format + # H2_Aa_b__H2_Aa_b to H2Ab + if len(allele) > 5: + match = H2_MIXMHC2PRED_ALLELE.match(allele) if match: # this ensures that netmhcpan output is normalized allele = "H2{gene}{protein}".format(gene=match.group(1), protein=match.group(2)) From 9b6f048a0ff50863b958279929c636cf2527cd4a Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Fri, 15 Sep 2023 14:40:20 +0200 Subject: [PATCH 59/83] some edits to adapt with instally.py --- .../MHC_predictors/MixMHCpred/mixmhc2pred.py | 23 +++++++++++-------- .../neoepitope_mhc_binding_annotator.py | 6 +---- neofox/references/references.py | 12 ++++++---- .../test_best_multiple_binder.py | 2 +- .../integration_tests/test_mixmhcpred.py | 4 ++-- neofox/tests/synthetic_data/data_generator.py | 2 +- 6 files changed, 25 insertions(+), 24 deletions(-) diff --git a/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py b/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py index bb1c766a..8ac8e613 100755 --- a/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py +++ b/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py @@ -23,8 +23,7 @@ from neofox.helpers.epitope_helper import EpitopeHelper from neofox.model.mhc_parser import MhcParser, get_alleles_by_gene -from neofox.references.references import DependenciesConfiguration, MhcDatabase, \ - ReferenceFolder, ORGANISM_HOMO_SAPIENS +from neofox.references.references import DependenciesConfiguration, MhcDatabase from neofox.helpers.runner import Runner @@ -55,8 +54,6 @@ def __init__(self, runner: Runner, configuration: DependenciesConfiguration, mhc self.mhc_parser = mhc_parser self.available_alleles = self._load_available_alleles(mhc_database) - #self.organism = references.organism - self.results = None def _load_available_alleles(self, mhc_database): @@ -68,10 +65,15 @@ def _load_available_alleles(self, mhc_database): alleles = pd.read_csv( self.configuration.mix_mhc2_pred_human_alleles_list, skiprows=2, sep="\t" ) + # run only else: - alleles = pd.read_csv( - self.configuration.mix_mhc2_pred_mouse_alleles_list, skiprows=2, sep="\t" - ) + # to test if the required PWMdef folder for mouse is downloaded + if self.configuration.mix_mhc2_pred_mouse_alleles_list is not None: + alleles = pd.read_csv( + self.configuration.mix_mhc2_pred_mouse_alleles_list, skiprows=2, sep="\t" + ) + else: + logger.warning("The PWMdef folder of mouse has not been downloaded.") return list(alleles["AlleleName"]) @@ -199,9 +201,10 @@ def _mixmhc2prediction(self, isoforms: List[str], potential_ligand_sequences: Li outtmp = intermediate_files.create_temp_file(prefix="mixmhc2pred", suffix=".txt") if self.mhc_database.is_homo_sapiens(): - pwm_path = '/home/nguyenhv/code/MixMHC2pred/2.0/PWMdef/PWMdef_Human/' + pwm_path = os.path.dirname(self.configuration.mix_mhc2_pred_human_alleles_list) else: - pwm_path = '/home/nguyenhv/code/MixMHC2pred/2.0/PWMdef/PWMdef_Mouse/' + #pwm_path = '/home/nguyenhv/code/MixMHC2pred/2.0/PWMdef/PWMdef_Mouse/' # reference folder + pwm_path = os.path.dirname(self.configuration.mix_mhc2_pred_mouse_alleles_list) cmd = [ self.configuration.mix_mhc2_pred, "-a", @@ -210,7 +213,7 @@ def _mixmhc2prediction(self, isoforms: List[str], potential_ligand_sequences: Li tmptxt, "-o", outtmp, - "-f", #add the full path of the folder + "-f", pwm_path, "--no_context" ] diff --git a/neofox/annotator/neoepitope_mhc_binding_annotator.py b/neofox/annotator/neoepitope_mhc_binding_annotator.py index 684484ef..c7dafe5f 100644 --- a/neofox/annotator/neoepitope_mhc_binding_annotator.py +++ b/neofox/annotator/neoepitope_mhc_binding_annotator.py @@ -40,7 +40,7 @@ def __init__(self, references: ReferenceFolder, configuration: DependenciesConfi runner=self.runner, configuration=configuration, mhc_parser=self.mhc_parser, blastp_runner=self.proteome_blastp_runner) self.mixmhcpred = MixMHCpred(self.runner, self.configuration, self.mhc_parser) - self.mixmhc2pred = MixMHC2pred(self.runner, self.configuration, self.mhc_parser) + self.mixmhc2pred = MixMHC2pred(self.runner, self.configuration, self.mhc_parser, self.mhc_database) self.prime = Prime(self.runner, self.configuration, self.mhc_parser) def get_mhc_binding_annotations(self, neoepitope: PredictedEpitope) -> PredictedEpitope: @@ -105,8 +105,6 @@ def _run_netmhcpan(self, neoepitope: PredictedEpitope) -> PredictedEpitope: sequence=neoepitope.mutated_peptide, alleles=netmhcpan_allele) annotated_neoepitope.affinity_mutated = mutated_epitope.affinity_mutated annotated_neoepitope.rank_mutated = mutated_epitope.rank_mutated - annotated_neoepitope.core = mutated_epitope.core - annotated_neoepitope.neofox_annotations = mutated_epitope.neofox_annotations wt_epitope = self.netmhcpan.mhc_prediction_peptide( sequence=neoepitope.wild_type_peptide, alleles=netmhcpan_allele) annotated_neoepitope.affinity_wild_type = wt_epitope.affinity_mutated @@ -123,8 +121,6 @@ def _run_netmhc2pan(self, neoepitope: PredictedEpitope) -> PredictedEpitope: mhc2_isoform=neoepitope.isoform_mhc_i_i) annotated_neoepitope.affinity_mutated = mutated_epitope.affinity_mutated annotated_neoepitope.rank_mutated = mutated_epitope.rank_mutated - annotated_neoepitope.core = mutated_epitope.core - annotated_neoepitope.neofox_annotations = mutated_epitope.neofox_annotations wt_epitope = self.netmhc2pan.mhc2_prediction_peptide( sequence=neoepitope.wild_type_peptide, mhc2_isoform=neoepitope.isoform_mhc_i_i) diff --git a/neofox/references/references.py b/neofox/references/references.py index 6261dd21..75bae363 100755 --- a/neofox/references/references.py +++ b/neofox/references/references.py @@ -77,8 +77,9 @@ HLA_DATABASE_AVAILABLE_ALLELES_FILE = "hla_database_allele_list.csv" H2_DATABASE_AVAILABLE_ALLELES_FILE = "h2_database_allele_list.csv" MIXMHCPRED_AVAILABLE_ALLELES_FILE = "allele_list.txt" -MIXMHC2PRED_AVAILABLE_HUMAN_ALLELES_FILE = "PWMdef/PWMdef_total/Alleles_list_Human.txt" -MIXMHC2PRED_AVAILABLE_MOUSE_ALLELES_FILE = "PWMdef/PWMdef_total/Alleles_list_Mouse.txt" +MIXMHC2PRED_AVAILABLE_HUMAN_ALLELES_FILE = "PWMdef/Alleles_list_Human.txt" +MIXMHC2PRED_PWM_MOUSE = "MixMHC2pred_PWMdef_Mouse" +MIXMHC2PRED_AVAILABLE_MOUSE_ALLELES_FILE = "PWMdef_Mouse/Alleles_list_Mouse.txt" PRIME_AVAILABLE_ALLELES_FILE = "alleles.txt" @@ -134,9 +135,10 @@ def __init__(self): if self.mix_mhc2_pred is not None: self.mix_mhc2_pred_human_alleles_list = os.path.join( os.path.dirname(self.mix_mhc2_pred), MIXMHC2PRED_AVAILABLE_HUMAN_ALLELES_FILE) - self.mix_mhc2_pred_mouse_alleles_list = os.path.join( - os.path.dirname(self.mix_mhc2_pred), MIXMHC2PRED_AVAILABLE_MOUSE_ALLELES_FILE - ) + # run this only when the PWMdef_Mouse was downloaded + if os.path.isdir(os.path.join(neofox.REFERENCE_FOLDER_ENV, MIXMHC2PRED_PWM_MOUSE)): + self.mix_mhc2_pred_mouse_alleles_list = os.path.join( + neofox.REFERENCE_FOLDER_ENV, MIXMHC2PRED_PWM_MOUSE, MIXMHC2PRED_AVAILABLE_MOUSE_ALLELES_FILE) else: self.mix_mhc2_pred_human_alleles_list = None self.mix_mhc2_pred_mouse_alleles_list = None diff --git a/neofox/tests/integration_tests/test_best_multiple_binder.py b/neofox/tests/integration_tests/test_best_multiple_binder.py index d9e6693b..83de9319 100755 --- a/neofox/tests/integration_tests/test_best_multiple_binder.py +++ b/neofox/tests/integration_tests/test_best_multiple_binder.py @@ -346,5 +346,5 @@ def test_generator_rate_mhcII(self): generator_rate_ADN = best_multiple.determine_number_of_alternative_binders(predictions=paired_predictions) generator_rate_CDN = best_multiple.determine_number_of_binders(predictions=paired_predictions) - self.assertEqual(generator_rate_ADN, 6) + self.assertEqual(generator_rate_ADN, 4) self.assertEqual(generator_rate_CDN, 0) diff --git a/neofox/tests/integration_tests/test_mixmhcpred.py b/neofox/tests/integration_tests/test_mixmhcpred.py index 3b147bfb..42181044 100755 --- a/neofox/tests/integration_tests/test_mixmhcpred.py +++ b/neofox/tests/integration_tests/test_mixmhcpred.py @@ -40,8 +40,8 @@ def setUp(self): runner=self.runner, configuration=self.configuration, mhc_parser=mhc_parser ) self.mixmhc2pred = MixMHC2pred( - runner=self.runner, configuration=self.configuration, mhc_parser=mhc_parser - ) + runner=self.runner, configuration=self.configuration, mhc_parser=mhc_parser, + mhc_database=self.references.get_mhc_database()) self.hla_database = self.references.get_mhc_database() self.test_mhc_one = integration_test_tools.get_hla_one_test(self.hla_database) self.test_mhc_two = integration_test_tools.get_hla_two_test(self.hla_database) diff --git a/neofox/tests/synthetic_data/data_generator.py b/neofox/tests/synthetic_data/data_generator.py index 1adb677a..caba2110 100644 --- a/neofox/tests/synthetic_data/data_generator.py +++ b/neofox/tests/synthetic_data/data_generator.py @@ -23,7 +23,7 @@ def __init__(self, reference_folder: ReferenceFolder, configuration: Dependencie mhc1_alleles = mixmhcpred_alleles.union(netmhcpan_alleles) mixmhc2pred_alleles = set(self.load_mhc2_alleles( - MixMHC2pred(runner=None, configuration=configuration, mhc_parser=None).available_alleles)) + MixMHC2pred(runner=None, configuration=configuration, mhc_parser=None, mhc_database=self.hla_database).available_alleles)) netmhc2pan_alleles = set(self.load_mhc2_alleles( reference_folder.get_available_alleles().get_available_mhc_ii())) mhc2_isoforms = mixmhc2pred_alleles.union(netmhc2pan_alleles) From 7d5416fe91ffd5e849e63baf178b4d92f6f921fd Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Fri, 15 Sep 2023 14:57:34 +0200 Subject: [PATCH 60/83] config for download PWMdef mouse --- neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py | 9 ++++++--- neofox/references/references.py | 11 +++++++---- 2 files changed, 13 insertions(+), 7 deletions(-) diff --git a/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py b/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py index bb1c766a..1e1b082d 100755 --- a/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py +++ b/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py @@ -69,9 +69,12 @@ def _load_available_alleles(self, mhc_database): self.configuration.mix_mhc2_pred_human_alleles_list, skiprows=2, sep="\t" ) else: - alleles = pd.read_csv( - self.configuration.mix_mhc2_pred_mouse_alleles_list, skiprows=2, sep="\t" - ) + if self.configuration.mix_mhc2_pred_mouse_alleles_list is not None: + alleles = pd.read_csv( + self.configuration.mix_mhc2_pred_mouse_alleles_list, skiprows=2, sep="\t" + ) + else: + logger.error("The PWMdef for Mouse was not downloaded.") return list(alleles["AlleleName"]) diff --git a/neofox/references/references.py b/neofox/references/references.py index 6261dd21..dcbf5e27 100755 --- a/neofox/references/references.py +++ b/neofox/references/references.py @@ -77,8 +77,9 @@ HLA_DATABASE_AVAILABLE_ALLELES_FILE = "hla_database_allele_list.csv" H2_DATABASE_AVAILABLE_ALLELES_FILE = "h2_database_allele_list.csv" MIXMHCPRED_AVAILABLE_ALLELES_FILE = "allele_list.txt" -MIXMHC2PRED_AVAILABLE_HUMAN_ALLELES_FILE = "PWMdef/PWMdef_total/Alleles_list_Human.txt" -MIXMHC2PRED_AVAILABLE_MOUSE_ALLELES_FILE = "PWMdef/PWMdef_total/Alleles_list_Mouse.txt" +MIXMHC2PRED_AVAILABLE_HUMAN_ALLELES_FILE = "Alleles_list_Human.txt" +MIXMHC2PRED_PWM="MixMHC2pred" +MIXMHC2PRED_AVAILABLE_MOUSE_ALLELES_FILE = "PWMdef_Mouse/Alleles_list_Mouse.txt" PRIME_AVAILABLE_ALLELES_FILE = "alleles.txt" @@ -134,8 +135,10 @@ def __init__(self): if self.mix_mhc2_pred is not None: self.mix_mhc2_pred_human_alleles_list = os.path.join( os.path.dirname(self.mix_mhc2_pred), MIXMHC2PRED_AVAILABLE_HUMAN_ALLELES_FILE) - self.mix_mhc2_pred_mouse_alleles_list = os.path.join( - os.path.dirname(self.mix_mhc2_pred), MIXMHC2PRED_AVAILABLE_MOUSE_ALLELES_FILE + # make sure that the PWMdef for Mouse was downloaded + if os.listdir(os.path.join(os.path.dirname(self.mix_mhc2_pred), MIXMHC2PRED_AVAILABLE_MOUSE_ALLELES_FILE)): + self.mix_mhc2_pred_mouse_alleles_list = os.path.join( + os.path.dirname(self.mix_mhc2_pred), MIXMHC2PRED_AVAILABLE_MOUSE_ALLELES_FILE ) else: self.mix_mhc2_pred_human_alleles_list = None From 46fc8261bd2dcf8a158e4672ddaf0d4d1ae38169 Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Sat, 16 Sep 2023 09:03:18 +0200 Subject: [PATCH 61/83] MixMHC2pred allele PWM download for mouse in installer.py --- neofox/__init__.py | 2 +- neofox/command_line.py | 10 +++++++- neofox/references/installer.py | 45 +++++++++++++++++++++++++++++++--- 3 files changed, 51 insertions(+), 6 deletions(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index de59c270..fd361f58 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b28" +VERSION = "1.1.0b29" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" diff --git a/neofox/command_line.py b/neofox/command_line.py index 765ef1a5..f18f6665 100755 --- a/neofox/command_line.py +++ b/neofox/command_line.py @@ -51,17 +51,25 @@ def neofox_configure(): action="store_true", help="install the R dependencies automatically", ) + parser.add_argument( + "--install-mouse-mixmhc2pred", + dest="install_mouse_mixmhc2pred", + action="store_true", + help="get the mouse allele PWMs required to run MixMHC2pred for mouse", + ) args = parser.parse_args() reference_folder = args.reference_folder install_r_dependencies = args.install_r_dependencies + install_mouse_mixmhc2pred = args.install_mouse_mixmhc2pred # makes sure that the output folder exists os.makedirs(reference_folder, exist_ok=True) logger.info("Starting the installation of references") NeofoxReferenceInstaller( - reference_folder=reference_folder, install_r_dependencies=install_r_dependencies + reference_folder=reference_folder, install_r_dependencies=install_r_dependencies, + install_mouse_mixmhc2pred=install_mouse_mixmhc2pred ).install() logger.info("Finished the installation succesfully!") diff --git a/neofox/references/installer.py b/neofox/references/installer.py index 769f0ac3..cd97fbc1 100644 --- a/neofox/references/installer.py +++ b/neofox/references/installer.py @@ -26,6 +26,7 @@ NETMHCPAN_AVAILABLE_ALLELES_MICE_FILE, NETMHC2PAN_AVAILABLE_ALLELES_MICE_FILE, MUS_MUSCULUS_FASTA, PREFIX_MUS_MUSCULUS, MUS_MUSCULUS_PICKLE, IEDB_FASTA_MUS_MUSCULUS, IEDB_BLAST_PREFIX_HOMO_SAPIENS, IEDB_BLAST_PREFIX_MUS_MUSCULUS, H2_DATABASE_AVAILABLE_ALLELES_FILE, RESOURCES_VERSIONS, + MIXMHC2PRED_PWM ) from logzero import logger @@ -41,13 +42,16 @@ IEDB_URL = 'http://www.iedb.org/downloader.php?file_name=doc/tcell_full_v3.zip' +MIXMHC2PRED_PWM_MOUSE_URL = "ec2-18-188-210-66.us-east-2.compute.amazonaws.com:4000/data/PWMdef/PWMdef_Mouse.zip" + class NeofoxReferenceInstaller(object): - def __init__(self, reference_folder, install_r_dependencies=False): + def __init__(self, reference_folder, install_r_dependencies=False, install_mouse_mixmhc2pred=False): self.config = DependenciesConfigurationForInstaller() self.runner = Runner() self.reference_folder = reference_folder self.install_r_dependencies = install_r_dependencies + self.install_mouse_mixmhc2pred = install_mouse_mixmhc2pred def install(self): # ensures the reference folder exists @@ -65,14 +69,19 @@ def install(self): self._install_r_dependencies() else: logger.warning("R dependencies will need to be installed manually") + if self.install_mouse_mixmhc2pred: + mixmhc2pred_resources = self._set_mixmhc2pred_pwms() + else: + logger.warning("MixMHC2pred mouse alleles have to be installed manually") self._save_resources_versions( iedb_resource=iedb_resource, hla_resource=hla_resource, - proteome_resources=proteome_resources + proteome_resources=proteome_resources, + mixmhc2pred_resources=mixmhc2pred_resources ) def _save_resources_versions( - self, iedb_resource, hla_resource, proteome_resources): + self, iedb_resource, hla_resource, proteome_resources, mixmhc2pred_resources): download_timestamp = datetime.today().strftime('%Y%m%d%H%M%S') resources_version_file = os.path.join(self.reference_folder, RESOURCES_VERSIONS) @@ -81,6 +90,8 @@ def _save_resources_versions( hla_resource.download_timestamp = download_timestamp for r in proteome_resources: r.download_timestamp = download_timestamp + for r in mixmhc2pred_resources: + r.download_timestamp = download_timestamp resources_version = [ Resource(name="netMHCpan", version="4.1"), @@ -89,7 +100,7 @@ def _save_resources_versions( Resource(name="mixMHC2pred", version="1.2"), iedb_resource, hla_resource - ] + proteome_resources + ] + proteome_resources + mixmhc2pred_resources json.dump([r.to_dict() for r in resources_version], open(resources_version_file, "w"), indent=4) @@ -347,6 +358,32 @@ def _install_r_dependencies(self): ) self._run_command(cmd) + def _set_mixmhc2pred_pwms(self): + # Downloads PWMs of other species than human from http://mixmhc2pred.gfellerlab.org/PWMdef + # Currently only mouse is supported and downloaded + logger.info("Installing MixMHC2pred for mouse...") + + # reference folder path where the MixMHC2pred PWM directories are downloaded into + mixmhc2pred_pwm_path = os.path.join(self.reference_folder, MIXMHC2PRED_PWM) + os.makedirs(mixmhc2pred_pwm_path, exist_ok=True) + # the name of the zip file that will be downloaded + zip_file = os.path.basename(MIXMHC2PRED_PWM_MOUSE_URL) + pwm_zip_file = os.path.join(mixmhc2pred_pwm_path, zip_file) + + url = MIXMHC2PRED_PWM_MOUSE_URL + + # download the allele PWMs + cmd = f"wget {url} -O {pwm_zip_file}" + self._run_command(cmd) + hash = self._get_md5_hash(pwm_zip_file) + # unzip the downloaded PWMs + cmd = f"unzip -o {pwm_zip_file} -d {mixmhc2pred_pwm_path}" + self._run_command(cmd) + + return [ + Resource(name="MixMHC2pred_PWM_Mouse", url=MIXMHC2PRED_PWM_MOUSE_URL, hash=hash), + ] + def _run_command(self, cmd): logger.info(cmd) process = subprocess.Popen( From e1b89a69789c75165d64d2340e37781d0305c22f Mon Sep 17 00:00:00 2001 From: Franziska Lang Date: Mon, 18 Sep 2023 09:04:01 +0200 Subject: [PATCH 62/83] adapt usage of vaf in expression.py --- neofox/published_features/expression.py | 29 +++++++++++----------- neofox/tests/unit_tests/test_expression.py | 24 ++++++++++-------- 2 files changed, 29 insertions(+), 24 deletions(-) diff --git a/neofox/published_features/expression.py b/neofox/published_features/expression.py index 07f4d7a3..d7d0c6d9 100755 --- a/neofox/published_features/expression.py +++ b/neofox/published_features/expression.py @@ -18,8 +18,7 @@ # You should have received a copy of the GNU General Public License # along with this program. If not, see .# from typing import List -from logzero import logger -from neofox.model.neoantigen import Annotation, Neoantigen, Patient +from neofox.model.neoantigen import Annotation, Neoantigen from neofox.model.factories import AnnotationFactory @@ -27,17 +26,17 @@ class Expression: @staticmethod def _get_expression_annotation( - transcript_gene_expression: float, vaf_rna: float + transcript_gene_expression: float, vaf: float ) -> float: """ - This function calculates the product of VAF in RNA and transcript expression + This function calculates the product of VAF and transcript expression to reflect the expression of the mutated transcript """ expression_mut = None try: expression_mut = ( - transcript_gene_expression * vaf_rna - if vaf_rna is not None and vaf_rna >= 0.0 + transcript_gene_expression * vaf + if vaf is not None and vaf >= 0.0 else None ) except (TypeError, ValueError): @@ -46,15 +45,17 @@ def _get_expression_annotation( def get_annotations(self, neoantigen: Neoantigen) -> List[Annotation]: - vaf = neoantigen.rna_variant_allele_frequency - if vaf is None or vaf == -1: - vaf = neoantigen.dna_variant_allele_frequency - return [ AnnotationFactory.build_annotation( - name="Mutated_rnaExpression", value=self._get_expression_annotation( - transcript_gene_expression=neoantigen.rna_expression, vaf_rna=vaf)), + name="Mutated_rnaExpression_fromRNA", value=self._get_expression_annotation( + transcript_gene_expression=neoantigen.rna_expression, vaf=neoantigen.rna_variant_allele_frequency)), + AnnotationFactory.build_annotation( + name="Mutated_rnaExpression_fromDNA", value=self._get_expression_annotation( + transcript_gene_expression=neoantigen.rna_expression, vaf=neoantigen.dna_variant_allele_frequency)), + AnnotationFactory.build_annotation( + name="Mutated_imputedGeneExpression_fromRNA", value=self._get_expression_annotation( + transcript_gene_expression=neoantigen.imputed_gene_expression, vaf=neoantigen.rna_variant_allele_frequency)), AnnotationFactory.build_annotation( - name="Mutated_imputedGeneExpression", value=self._get_expression_annotation( - transcript_gene_expression=neoantigen.imputed_gene_expression, vaf_rna=vaf)) + name="Mutated_imputedGeneExpression_fromDNA", value=self._get_expression_annotation( + transcript_gene_expression=neoantigen.imputed_gene_expression, vaf=neoantigen.dna_variant_allele_frequency)) ] diff --git a/neofox/tests/unit_tests/test_expression.py b/neofox/tests/unit_tests/test_expression.py index dcd54f63..ba1e382b 100755 --- a/neofox/tests/unit_tests/test_expression.py +++ b/neofox/tests/unit_tests/test_expression.py @@ -20,7 +20,6 @@ from unittest import TestCase from neofox.model.factories import NOT_AVAILABLE_VALUE, NeoantigenFactory -from neofox.model.neoantigen import Neoantigen from neofox.published_features.expression import Expression @@ -33,15 +32,22 @@ def test_calculate_expression_mutation(self): neoantigen = NeoantigenFactory.build_neoantigen( rna_expression=12.0, dna_variant_allele_frequency=0.2, patient_identifier="patient1", mutated_xmer="DDDDD") - result = self.expression.get_annotations(neoantigen=neoantigen)[0] - self.assertGreater(float(result.value), 0.0) + results = self.expression.get_annotations(neoantigen=neoantigen) + val = [e.value for e in results if e.name == "Mutated_rnaExpression_fromRNA"] + print(val[0]) + result_rna = self.expression.get_annotations(neoantigen=neoantigen)[0] + result_dna = self.expression.get_annotations(neoantigen=neoantigen)[1] + self.assertEqual(result_rna.value, NOT_AVAILABLE_VALUE) + self.assertEqual(float(result_dna.value), 2.4) # no reads for mut neoantigen = NeoantigenFactory.build_neoantigen( rna_expression=12.0, dna_variant_allele_frequency=0.0, patient_identifier="patient1", mutated_xmer="DDDDD") - result = self.expression.get_annotations(neoantigen=neoantigen)[0] - self.assertEqual(result.value, "0") + result_rna = self.expression.get_annotations(neoantigen=neoantigen)[0] + result_dna = self.expression.get_annotations(neoantigen=neoantigen)[1] + self.assertEqual(float(result_dna.value), 0) + self.assertEqual(result_rna.value, NOT_AVAILABLE_VALUE) # no reads for mut/wt neoantigen = NeoantigenFactory.build_neoantigen( @@ -49,9 +55,7 @@ def test_calculate_expression_mutation(self): mutated_xmer="DDDDD") result = self.expression.get_annotations(neoantigen=neoantigen)[0] self.assertEqual(result.value, NOT_AVAILABLE_VALUE) - - neoantigen = NeoantigenFactory.build_neoantigen( - rna_expression=None, dna_variant_allele_frequency=-1, rna_variant_allele_frequency=-1, - patient_identifier="patient1", mutated_xmer="DDDDD") - result = self.expression.get_annotations(neoantigen=neoantigen)[0] + result = self.expression.get_annotations(neoantigen=neoantigen)[1] self.assertEqual(result.value, NOT_AVAILABLE_VALUE) + + From 6ee65794d610a7f99aea3c046b8aae77618a9805 Mon Sep 17 00:00:00 2001 From: Franziska Lang Date: Mon, 18 Sep 2023 09:04:33 +0200 Subject: [PATCH 63/83] adapt usage of vaf in priority score --- neofox/published_features/priority_score.py | 101 ++++++++++++------ .../tests/unit_tests/test_priority_score.py | 34 ++---- 2 files changed, 79 insertions(+), 56 deletions(-) diff --git a/neofox/published_features/priority_score.py b/neofox/published_features/priority_score.py index 49a120dc..02d4dac0 100755 --- a/neofox/published_features/priority_score.py +++ b/neofox/published_features/priority_score.py @@ -21,9 +21,8 @@ # import modules import math from typing import List - from neofox.helpers.epitope_helper import EpitopeHelper -from neofox.model.neoantigen import Annotation, PredictedEpitope, Neoantigen, Patient +from neofox.model.neoantigen import Annotation, PredictedEpitope, Neoantigen from neofox.model.factories import AnnotationFactory from neofox.MHC_predictors.netmhcpan.combine_netmhcpan_pred_multiple_binders import ( BestAndMultipleBinder, @@ -43,8 +42,7 @@ def calc_logistic_function(self, mhc_score): def calc_priority_score( self, - vaf_dna, - vaf_rna, + vaf, transcript_gene_expr, no_mismatch, score_mut, @@ -53,15 +51,12 @@ def calc_priority_score( ): """ This function calculates the Priority Score using parameters for mhc I. + Bjerregard, 2017, Cancer Immunol Immunother + https://doi.org/10.1007/s00262-017-2001-3 """ priority_score = None - vaf = None try: - if vaf_dna is not None and vaf_dna != -1: - vaf = vaf_dna - elif vaf_rna is not None and vaf_rna != -1: - vaf = vaf_rna - if vaf: + if vaf is not None and vaf != -1: l_mut = self.calc_logistic_function(score_mut) l_wt = self.calc_logistic_function(score_wt) priority_score = self.mupexi( @@ -94,29 +89,42 @@ def get_annotations( returns number of mismatches between best MHCI / MHC II epitopes (rank) and their corresponding WTs """ num_mismatches_mhc1 = None - priority_score = None - priority_score_imputed = None + priority_score_dna = None + priority_score_rna = None + priority_score_imputed_dna = None + priority_score_imputed_rna = None if netmhcpan.best_epitope_by_rank.wild_type_peptide and netmhcpan.best_epitope_by_rank.mutated_peptide: num_mismatches_mhc1 = EpitopeHelper.number_of_mismatches( epitope_wild_type=netmhcpan.best_epitope_by_rank.wild_type_peptide, epitope_mutation=netmhcpan.best_epitope_by_rank.mutated_peptide, ) - vaf_rna = neoantigen.dna_variant_allele_frequency - if vaf_rna is None: - vaf_rna = neoantigen.rna_variant_allele_frequency - priority_score = self.calc_priority_score( - vaf_dna=neoantigen.dna_variant_allele_frequency, - vaf_rna=vaf_rna, + priority_score_dna = self.calc_priority_score( + vaf=neoantigen.dna_variant_allele_frequency, + transcript_gene_expr=neoantigen.rna_expression, + no_mismatch=num_mismatches_mhc1, + score_mut=netmhcpan.best_epitope_by_rank.rank_mutated, + score_wt=netmhcpan.best_epitope_by_rank.rank_wild_type, + mut_not_in_prot=mut_not_in_prot, + ) + priority_score_rna = self.calc_priority_score( + vaf=neoantigen.rna_variant_allele_frequency, transcript_gene_expr=neoantigen.rna_expression, no_mismatch=num_mismatches_mhc1, score_mut=netmhcpan.best_epitope_by_rank.rank_mutated, score_wt=netmhcpan.best_epitope_by_rank.rank_wild_type, mut_not_in_prot=mut_not_in_prot, ) - priority_score_imputed = self.calc_priority_score( - vaf_dna=neoantigen.dna_variant_allele_frequency, - vaf_rna=vaf_rna, + priority_score_imputed_dna = self.calc_priority_score( + vaf=neoantigen.dna_variant_allele_frequency, + transcript_gene_expr=neoantigen.imputed_gene_expression, + no_mismatch=num_mismatches_mhc1, + score_mut=netmhcpan.best_epitope_by_rank.rank_mutated, + score_wt=netmhcpan.best_epitope_by_rank.rank_wild_type, + mut_not_in_prot=mut_not_in_prot, + ) + priority_score_imputed_rna = self.calc_priority_score( + vaf=neoantigen.rna_variant_allele_frequency, transcript_gene_expr=neoantigen.imputed_gene_expression, no_mismatch=num_mismatches_mhc1, score_mut=netmhcpan.best_epitope_by_rank.rank_mutated, @@ -129,13 +137,23 @@ def get_annotations( ), # priority score with rank score AnnotationFactory.build_annotation( - value=priority_score, - name="Priority_score", + value=priority_score_dna, + name="Priority_score_fromDNA", + ), + # imputed priority score with rank score + AnnotationFactory.build_annotation( + value=priority_score_imputed_rna, + name="Priority_score_imputed_fromRNA" + ), + # priority score with rank score f + AnnotationFactory.build_annotation( + value=priority_score_rna, + name="Priority_score_fromRNA", ), # imputed priority score with rank score AnnotationFactory.build_annotation( - value=priority_score_imputed, - name="Priority_score_imputed" + value=priority_score_imputed_dna, + name="Priority_score_imputed_fromDNA" ) ] return annotations @@ -145,8 +163,7 @@ def get_annotations_epitope_mhci(self, epitope: PredictedEpitope, vaf_tumor, tra return [ AnnotationFactory.build_annotation( value=self.calc_priority_score( - vaf_dna=vaf_tumor, - vaf_rna=vaf_rna, + vaf=vaf_tumor, transcript_gene_expr=transcript_exp, no_mismatch=int(EpitopeHelper.get_annotation_by_name( epitope.neofox_annotations.annotations, name='number_of_mismatches')), @@ -154,11 +171,10 @@ def get_annotations_epitope_mhci(self, epitope: PredictedEpitope, vaf_tumor, tra score_wt=epitope.rank_wild_type, mut_not_in_prot=bool(EpitopeHelper.get_annotation_by_name( epitope.neofox_annotations.annotations, name='mutation_not_found_in_proteome'))), - name='Priority_score'), + name='Priority_score_fromDNA'), AnnotationFactory.build_annotation( value=self.calc_priority_score( - vaf_dna=vaf_tumor, - vaf_rna=vaf_rna, + vaf=vaf_tumor, transcript_gene_expr=gene_exp, no_mismatch=int(EpitopeHelper.get_annotation_by_name( epitope.neofox_annotations.annotations, name='number_of_mismatches')), @@ -166,5 +182,28 @@ def get_annotations_epitope_mhci(self, epitope: PredictedEpitope, vaf_tumor, tra score_wt=epitope.rank_wild_type, mut_not_in_prot=bool(EpitopeHelper.get_annotation_by_name( epitope.neofox_annotations.annotations, name='mutation_not_found_in_proteome'))), - name='Priority_score_imputed'), + name='Priority_score_imputed_fromDNA'), + AnnotationFactory.build_annotation( + value=self.calc_priority_score( + vaf=vaf_rna, + transcript_gene_expr=transcript_exp, + no_mismatch=int(EpitopeHelper.get_annotation_by_name( + epitope.neofox_annotations.annotations, name='number_of_mismatches')), + score_mut=epitope.rank_mutated, + score_wt=epitope.rank_wild_type, + mut_not_in_prot=bool(EpitopeHelper.get_annotation_by_name( + epitope.neofox_annotations.annotations, name='mutation_not_found_in_proteome'))), + name='Priority_score_fromRNA'), + AnnotationFactory.build_annotation( + value=self.calc_priority_score( + vaf=vaf_rna, + transcript_gene_expr=gene_exp, + no_mismatch=int(EpitopeHelper.get_annotation_by_name( + epitope.neofox_annotations.annotations, name='number_of_mismatches')), + score_mut=epitope.rank_mutated, + score_wt=epitope.rank_wild_type, + mut_not_in_prot=bool(EpitopeHelper.get_annotation_by_name( + epitope.neofox_annotations.annotations, name='mutation_not_found_in_proteome'))), + name='Priority_score_imputed_fromDNA'), + ] diff --git a/neofox/tests/unit_tests/test_priority_score.py b/neofox/tests/unit_tests/test_priority_score.py index a9e87dbc..c28530bf 100755 --- a/neofox/tests/unit_tests/test_priority_score.py +++ b/neofox/tests/unit_tests/test_priority_score.py @@ -19,15 +19,13 @@ from unittest import TestCase from neofox.published_features.priority_score import PriorityScore - class TestPriorityScore(TestCase): def setUp(self): self.priority_calculator = PriorityScore() def test_priority(self): result = self.priority_calculator.calc_priority_score( - vaf_dna=0.35, - vaf_rna=0.33, + vaf=0.35, transcript_gene_expr=12, no_mismatch=1, score_mut=1.1, @@ -37,28 +35,16 @@ def test_priority(self): self.assertGreater(result, 0) result = self.priority_calculator.calc_priority_score( - vaf_dna=None, - vaf_rna=0.33, - transcript_gene_expr=12, - no_mismatch=1, - score_mut=1.1, - score_wt=10, - mut_not_in_prot=True, - ) - self.assertGreater(result, 0) - result = self.priority_calculator.calc_priority_score( - vaf_dna=0.35, - vaf_rna=None, + vaf=None, transcript_gene_expr=12, no_mismatch=1, score_mut=1.1, score_wt=10, mut_not_in_prot=True, ) - self.assertGreater(result, 0) + self.assertEqual(result, None) result = self.priority_calculator.calc_priority_score( - vaf_dna=None, - vaf_rna=-1, + vaf=-1, transcript_gene_expr=12, no_mismatch=1, score_mut=1.1, @@ -67,8 +53,7 @@ def test_priority(self): ) self.assertEqual(result, None) result = self.priority_calculator.calc_priority_score( - vaf_dna=0.35, - vaf_rna=0.33, + vaf=0.35, transcript_gene_expr=None, no_mismatch=1, score_mut=1.1, @@ -77,12 +62,11 @@ def test_priority(self): ) self.assertEqual(result, None) result = self.priority_calculator.calc_priority_score( - vaf_dna=0.35, - vaf_rna=0.33, - transcript_gene_expr=None, + vaf=0.35, + transcript_gene_expr=500, no_mismatch=1, - score_mut=1.1, + score_mut=0.5, score_wt=10, mut_not_in_prot=True, ) - self.assertEqual(result, None) + self.assertEqual(result, 0.34980652747707675) From 35ed4eb9c6e2873c522ad376800de8cb8b753369 Mon Sep 17 00:00:00 2001 From: Franziska Lang Date: Mon, 18 Sep 2023 09:05:12 +0200 Subject: [PATCH 64/83] adapt usage of vaf in vaxrank --- neofox/annotator/neoantigen_annotator.py | 5 +++-- neofox/published_features/vaxrank/vaxrank.py | 2 ++ 2 files changed, 5 insertions(+), 2 deletions(-) diff --git a/neofox/annotator/neoantigen_annotator.py b/neofox/annotator/neoantigen_annotator.py index ea0be963..7325a0a6 100755 --- a/neofox/annotator/neoantigen_annotator.py +++ b/neofox/annotator/neoantigen_annotator.py @@ -218,11 +218,12 @@ def get_annotated_neoantigen(self, neoantigen: Neoantigen, patient: Patient, wit ) # vaxrank + # TODO: consider to calculate vaxrank with DNA VAF aswell if netmhcpan and netmhcpan.predictions: neoantigen.neofox_annotations.annotations.extend(VaxRank().get_annotations( epitope_predictions=netmhcpan.predictions, - expression_score=expression_annotation[0].value, - imputed_score=expression_annotation[1].value + expression_score=[e.value for e in expression_annotation if e.name == "Mutated_rnaExpression_fromRNA"][0], + imputed_score=[e.value for e in expression_annotation if e.name == "Mutated_imputedGeneExpression_fromRNA"][0] )) # hex diff --git a/neofox/published_features/vaxrank/vaxrank.py b/neofox/published_features/vaxrank/vaxrank.py index 30efb399..ce163124 100755 --- a/neofox/published_features/vaxrank/vaxrank.py +++ b/neofox/published_features/vaxrank/vaxrank.py @@ -43,6 +43,8 @@ def logistic_epitope_score( "The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes. adapted from: https://github.com/openvax/vaxrank/blob/master/vaxrank/epitope_prediction.py + Rubinsteyn, 2017, Front Immunol + https://doi.org/10.3389/fimmu.2017.01807 """ if ic50 >= ic50_cutoff: return 0.0 From b1daeb16a1a5bcdcf388257eecb039d3c0bfd832 Mon Sep 17 00:00:00 2001 From: Franziska Lang Date: Mon, 18 Sep 2023 09:19:08 +0200 Subject: [PATCH 65/83] adapt neofox test --- neofox/tests/integration_tests/test_neofox.py | 9 +++++---- 1 file changed, 5 insertions(+), 4 deletions(-) diff --git a/neofox/tests/integration_tests/test_neofox.py b/neofox/tests/integration_tests/test_neofox.py index 392c438b..e8b9921b 100755 --- a/neofox/tests/integration_tests/test_neofox.py +++ b/neofox/tests/integration_tests/test_neofox.py @@ -204,7 +204,7 @@ def test_neofox_model_input(self): ).get_annotations() self.assertEqual(5, len(annotations)) self.assertIsInstance(annotations[0], Neoantigen) - self.assertEqual(len(annotations[0].neofox_annotations.annotations),101) + self.assertEqual(len(annotations[0].neofox_annotations.annotations), 105) def test_neofox_without_mixmhcpreds(self): """ @@ -317,7 +317,7 @@ def test_neofox_with_config(self): assert False def test_neofox_without_mhc2(self): - """""" + neoantigens, patients = self._get_test_data() for p in patients: p.mhc2 = [] @@ -328,7 +328,7 @@ def test_neofox_without_mhc2(self): ).get_annotations() self.assertEqual(5, len(annotations)) self.assertIsInstance(annotations[0], Neoantigen) - self.assertEqual(len(annotations[0].neofox_annotations.annotations), 76) + self.assertEqual(len(annotations[0].neofox_annotations.annotations), 80) def test_neofox_without_mhc1(self): neoantigens, patients = self._get_test_data() @@ -341,7 +341,8 @@ def test_neofox_without_mhc1(self): ).get_annotations() self.assertEqual(5, len(annotations)) self.assertIsInstance(annotations[0], Neoantigen) - self.assertEqual(len(annotations[0].neofox_annotations.annotations), 46) + print(annotations[0].neofox_annotations.annotations) + self.assertEqual(len(annotations[0].neofox_annotations.annotations), 48) def test_gene_expression_imputation(self): neoantigens, patients = self._get_test_data() From cacdb03416af158acc7d6108926d30c5421f986c Mon Sep 17 00:00:00 2001 From: Franziska Lang Date: Mon, 18 Sep 2023 09:31:55 +0200 Subject: [PATCH 66/83] rm unncess code --- neofox/tests/unit_tests/test_expression.py | 2 -- 1 file changed, 2 deletions(-) diff --git a/neofox/tests/unit_tests/test_expression.py b/neofox/tests/unit_tests/test_expression.py index ba1e382b..19e9f2e4 100755 --- a/neofox/tests/unit_tests/test_expression.py +++ b/neofox/tests/unit_tests/test_expression.py @@ -33,8 +33,6 @@ def test_calculate_expression_mutation(self): rna_expression=12.0, dna_variant_allele_frequency=0.2, patient_identifier="patient1", mutated_xmer="DDDDD") results = self.expression.get_annotations(neoantigen=neoantigen) - val = [e.value for e in results if e.name == "Mutated_rnaExpression_fromRNA"] - print(val[0]) result_rna = self.expression.get_annotations(neoantigen=neoantigen)[0] result_dna = self.expression.get_annotations(neoantigen=neoantigen)[1] self.assertEqual(result_rna.value, NOT_AVAILABLE_VALUE) From 7b8644d1c61c7e6059599ec5530514b7bb9d69c1 Mon Sep 17 00:00:00 2001 From: Franziska Lang Date: Mon, 18 Sep 2023 09:32:23 +0200 Subject: [PATCH 67/83] increase version --- neofox/__init__.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index 4b281bfb..de59c270 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b27" +VERSION = "1.1.0b28" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" From 37e3403f893a550e3e3d1c0a2b422056ae83ba6a Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Mon, 18 Sep 2023 10:14:49 +0200 Subject: [PATCH 68/83] Moved mouse allele definition and PWM to ReferenceFolder class --- .../MHC_predictors/MixMHCpred/mixmhc2pred.py | 39 ++++++++++--------- .../neoantigen_mhc_binding_annotator.py | 9 +++-- neofox/references/references.py | 35 ++++++++++++----- 3 files changed, 51 insertions(+), 32 deletions(-) diff --git a/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py b/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py index 1e1b082d..70532d59 100755 --- a/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py +++ b/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py @@ -24,7 +24,8 @@ from neofox.model.mhc_parser import MhcParser, get_alleles_by_gene from neofox.references.references import DependenciesConfiguration, MhcDatabase, \ - ReferenceFolder, ORGANISM_HOMO_SAPIENS + ReferenceFolder, ORGANISM_HOMO_SAPIENS, \ + ORGANISM_MUS_MUSCULUS from neofox.helpers.runner import Runner @@ -48,33 +49,33 @@ class MixMHC2pred: ANNOTATION_PREFIX_WT = 'MixMHC2pred_WT' def __init__(self, runner: Runner, configuration: DependenciesConfiguration, mhc_parser: MhcParser, - mhc_database: MhcDatabase): + references: ReferenceFolder): self.runner = runner self.configuration = configuration - self.mhc_database = mhc_database self.mhc_parser = mhc_parser - self.available_alleles = self._load_available_alleles(mhc_database) - - #self.organism = references.organism + self.references = references + self.organism = references.organism + self.available_alleles = self._load_available_alleles() self.results = None - def _load_available_alleles(self, mhc_database): + def _load_available_alleles(self): """ - loads file with available HLA II alllels for MixMHC2pred prediction, returns set + loads file with available HLA II allels for MixMHC2pred prediction, returns set :return: """ - if mhc_database.is_homo_sapiens(): + if self.organism == ORGANISM_HOMO_SAPIENS: alleles = pd.read_csv( self.configuration.mix_mhc2_pred_human_alleles_list, skiprows=2, sep="\t" ) - else: - if self.configuration.mix_mhc2_pred_mouse_alleles_list is not None: + elif self.organism == ORGANISM_MUS_MUSCULUS: + if self.references.mixmhc2pred_alleles_list is not None: alleles = pd.read_csv( - self.configuration.mix_mhc2_pred_mouse_alleles_list, skiprows=2, sep="\t" + self.references.mixmhc2pred_alleles_list, skiprows=2, sep="\t" ) else: logger.error("The PWMdef for Mouse was not downloaded.") + return list(alleles["AlleleName"]) @@ -201,10 +202,11 @@ def _mixmhc2prediction(self, isoforms: List[str], potential_ligand_sequences: Li tmptxt = intermediate_files.create_temp_mixmhc2pred(potential_ligand_sequences, prefix="tmp_sequence_") outtmp = intermediate_files.create_temp_file(prefix="mixmhc2pred", suffix=".txt") - if self.mhc_database.is_homo_sapiens(): - pwm_path = '/home/nguyenhv/code/MixMHC2pred/2.0/PWMdef/PWMdef_Human/' + if self.organism == ORGANISM_HOMO_SAPIENS: + pwm_argument = "" else: - pwm_path = '/home/nguyenhv/code/MixMHC2pred/2.0/PWMdef/PWMdef_Mouse/' + pwm_dir = self.references.mixmhc2pred_pwm_dir + pwm_argument = f"-f {pwm_dir}" cmd = [ self.configuration.mix_mhc2_pred, "-a", @@ -213,8 +215,7 @@ def _mixmhc2prediction(self, isoforms: List[str], potential_ligand_sequences: Li tmptxt, "-o", outtmp, - "-f", #add the full path of the folder - pwm_path, + pwm_argument, "--no_context" ] self.runner.run_command(cmd) @@ -236,7 +237,7 @@ def run(self, mhc: List[Mhc2], neoantigen: Neoantigen, uniprot): neoantigen=neoantigen, lengths=[12, 13, 14, 15, 16, 17, 18, 19, 20, 21], uniprot=uniprot) if len(potential_ligand_sequences) > 0: - if self.mhc_database.is_homo_sapiens(): + if self.organism == ORGANISM_HOMO_SAPIENS: mhc2_alleles = self.transform_hla_ii_alleles_for_prediction(mhc) else: mhc2_alleles = self.transform_h2_alleles_for_prediction(mhc) @@ -253,7 +254,7 @@ def run_peptide(self, peptide: str, isoform: Mhc2Isoform) -> PredictedEpitope: Performs MixMHC2pred prediction for desired hla allele and writes result to temporary file. """ result = None - if self.mhc_database.is_homo_sapiens(): + if self.organism == ORGANISM_HOMO_SAPIENS: isoform_representation = self._get_mixmhc2_isoform_human_representation(isoform) else: isoform_representation = self._get_mixmhc2_isoform_mouse_representation(isoform) diff --git a/neofox/annotator/neoantigen_mhc_binding_annotator.py b/neofox/annotator/neoantigen_mhc_binding_annotator.py index b2707e4e..9394a2aa 100644 --- a/neofox/annotator/neoantigen_mhc_binding_annotator.py +++ b/neofox/annotator/neoantigen_mhc_binding_annotator.py @@ -24,6 +24,7 @@ def __init__(self, references: ReferenceFolder, configuration: DependenciesConfi self.organism = references.organism self.uniprot = uniprot self.proteome_blastp_runner = proteome_blastp_runner + self.references = references self.mhc_database = references.get_mhc_database() self.mhc_parser = MhcParser.get_mhc_parser(self.mhc_database) @@ -64,7 +65,8 @@ def get_mhc_binding_annotations(self, neoantigen: Neoantigen, patient: Patient): self.mhc_parser, neoantigen, patient, - self.mhc_database + self.mhc_database, + self.references ) # avoids running MixMHCpred and PRIME for non human organisms @@ -159,8 +161,9 @@ def _run_mixmhc2pred( mhc_parser: MhcParser, neoantigen: Neoantigen, patient: Patient, - mhc_database: MhcDatabase + mhc_database: MhcDatabase, + references: ReferenceFolder ): - mixmhc2 = MixMHC2pred(runner, configuration, mhc_parser, mhc_database) + mixmhc2 = MixMHC2pred(runner, configuration, mhc_parser, references) mixmhc2.run(mhc=patient.mhc2, neoantigen=neoantigen, uniprot=self.uniprot) return mixmhc2 \ No newline at end of file diff --git a/neofox/references/references.py b/neofox/references/references.py index dcbf5e27..20922716 100755 --- a/neofox/references/references.py +++ b/neofox/references/references.py @@ -77,9 +77,10 @@ HLA_DATABASE_AVAILABLE_ALLELES_FILE = "hla_database_allele_list.csv" H2_DATABASE_AVAILABLE_ALLELES_FILE = "h2_database_allele_list.csv" MIXMHCPRED_AVAILABLE_ALLELES_FILE = "allele_list.txt" -MIXMHC2PRED_AVAILABLE_HUMAN_ALLELES_FILE = "Alleles_list_Human.txt" +MIXMHC2PRED_AVAILABLE_HUMAN_ALLELES_FILE = "PWMdef/Alleles_list_Human.txt" MIXMHC2PRED_PWM="MixMHC2pred" -MIXMHC2PRED_AVAILABLE_MOUSE_ALLELES_FILE = "PWMdef_Mouse/Alleles_list_Mouse.txt" +MIXMHC2PRED_AVAILABLE_MOUSE_PWM_DIR = "PWMdef_Mouse" +MIXMHC2PRED_AVAILABLE_MOUSE_ALLELES_FILE = "Alleles_list_Mouse.txt" PRIME_AVAILABLE_ALLELES_FILE = "alleles.txt" @@ -132,17 +133,10 @@ def __init__(self): self.mix_mhc2_pred = self._check_and_load_binary( neofox.NEOFOX_MIXMHC2PRED_ENV, default_value=DEFAULT_MIXMHC2PRED, optional=True, path_search=False) + # set the available alleles for MixMHCpred if self.mix_mhc2_pred is not None: self.mix_mhc2_pred_human_alleles_list = os.path.join( os.path.dirname(self.mix_mhc2_pred), MIXMHC2PRED_AVAILABLE_HUMAN_ALLELES_FILE) - # make sure that the PWMdef for Mouse was downloaded - if os.listdir(os.path.join(os.path.dirname(self.mix_mhc2_pred), MIXMHC2PRED_AVAILABLE_MOUSE_ALLELES_FILE)): - self.mix_mhc2_pred_mouse_alleles_list = os.path.join( - os.path.dirname(self.mix_mhc2_pred), MIXMHC2PRED_AVAILABLE_MOUSE_ALLELES_FILE - ) - else: - self.mix_mhc2_pred_human_alleles_list = None - self.mix_mhc2_pred_mouse_alleles_list = None self.mix_mhc_pred = self._check_and_load_binary( neofox.NEOFOX_MIXMHCPRED_ENV, default_value=DEFAULT_MIXMHCPRED, optional=True, path_search=False) @@ -292,6 +286,16 @@ def __init__(self, organism=ORGANISM_HOMO_SAPIENS, verbose=False): self.mhc_database_filename, self.resources_versions_file ] + # set MixMHC2pred specific paths for non human mode + if not organism == ORGANISM_HOMO_SAPIENS: + self.mixmhc2pred_pwm = self._get_reference_file_name(MIXMHC2PRED_PWM) + self.mixmhc2pred_alleles_list = self._get_mixmhc2pred_alleles_list() + self.mixmhc2pred_pwm_dir = self._get_mixmhc2pred_pwm_dir() + self.resources.extend([self.mixmhc2pred_alleles_list, self.mixmhc2pred_pwm_dir]) + else: + self.mixmhc2pred_alleles_list = None + self.mixmhc2pred_pwm_dir = None + self._check_resources() self.resources_versions = self.get_resources_versions() if verbose: @@ -396,6 +400,17 @@ def _log_configuration(self): def _get_reference_file_name(self, file_name_suffix): return os.path.join(self.reference_genome_folder, file_name_suffix) + def _get_mixmhc2pred_alleles_list(self): + if self.organism == ORGANISM_MUS_MUSCULUS: + return os.path.join(self.mixmhc2pred_pwm, + MIXMHC2PRED_AVAILABLE_MOUSE_PWM_DIR, + MIXMHC2PRED_AVAILABLE_MOUSE_ALLELES_FILE) + + def _get_mixmhc2pred_pwm_dir(self): + if self.organism == ORGANISM_MUS_MUSCULUS: + return os.path.join(self.mixmhc2pred_pwm, + MIXMHC2PRED_AVAILABLE_MOUSE_PWM_DIR) + class AvailableAlleles(object): def __init__(self, references): From 25060a74dc54ef657d4f0084c8f2059092e2a58f Mon Sep 17 00:00:00 2001 From: Franziska Lang Date: Mon, 18 Sep 2023 11:31:48 +0200 Subject: [PATCH 69/83] rm unncessary code + fix tests --- neofox/neofox.py | 15 ++++----------- neofox/published_features/priority_score.py | 2 +- neofox/tests/integration_tests/test_neofox.py | 1 + 3 files changed, 6 insertions(+), 12 deletions(-) diff --git a/neofox/neofox.py b/neofox/neofox.py index 7fb7e614..0c8b0761 100755 --- a/neofox/neofox.py +++ b/neofox/neofox.py @@ -105,16 +105,9 @@ def __init__( self._validate_input_data() - # retrieve from the data, if RNA-seq was available - # add this information to patient model - expression_per_patient = {self.patients[patient].identifier: [] for patient in self.patients} - for neoantigen in self.neoantigens: - expression_per_patient[neoantigen.patient_identifier].append(neoantigen.rna_expression) - # only performs the expression imputation for humans + # annotate TCGA gene expression if self.reference_folder.organism == ORGANISM_HOMO_SAPIENS: - # impute expresssion from TCGA, ONLY if isRNAavailable = False for given patient, - # otherwise original values is reported # NOTE: this must happen after validation to avoid uncaptured errors due to missing patients # NOTE: add gene expression to neoantigen candidate model self.neoantigens = self._conditional_expression_imputation() @@ -128,15 +121,15 @@ def _conditional_expression_imputation(self) -> List[Neoantigen]: neoantigens_transformed = [] for neoantigen in self.neoantigens: - expression_value = neoantigen.rna_expression + patient = self.patients[neoantigen.patient_identifier] neoantigen_transformed = neoantigen + gene_expression = expression_annotator.get_gene_expression_annotation( gene_name=neoantigen.gene, tcga_cohort=patient.tumor_type ) - neoantigen_transformed.rna_expression = expression_value - neoantigen.imputed_gene_expression = gene_expression + neoantigen_transformed.imputed_gene_expression = gene_expression neoantigens_transformed.append(neoantigen_transformed) return neoantigens_transformed diff --git a/neofox/published_features/priority_score.py b/neofox/published_features/priority_score.py index 02d4dac0..e849e174 100755 --- a/neofox/published_features/priority_score.py +++ b/neofox/published_features/priority_score.py @@ -204,6 +204,6 @@ def get_annotations_epitope_mhci(self, epitope: PredictedEpitope, vaf_tumor, tra score_wt=epitope.rank_wild_type, mut_not_in_prot=bool(EpitopeHelper.get_annotation_by_name( epitope.neofox_annotations.annotations, name='mutation_not_found_in_proteome'))), - name='Priority_score_imputed_fromDNA'), + name='Priority_score_imputed_fromRNA'), ] diff --git a/neofox/tests/integration_tests/test_neofox.py b/neofox/tests/integration_tests/test_neofox.py index e8b9921b..531430e8 100755 --- a/neofox/tests/integration_tests/test_neofox.py +++ b/neofox/tests/integration_tests/test_neofox.py @@ -630,6 +630,7 @@ def test_with_all_neoepitopes(self): self.assertTrue(found_recognition_potential) + df_epitopes_mhci = ModelConverter.annotations2epitopes_table(annotations, mhc=neofox.MHC_I) self.assertFalse(any(c.startswith('isoformMhcII') for c in df_epitopes_mhci.columns)) From 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z|4>g}Lpz^)`uB1091Iiur}eqk#g!mIPx;>>{(lKz-e*axBL(q86D3}w84CWR?f(F< C-a|G3 diff --git a/docs/source/03_01_input_data.md b/docs/source/03_01_input_data.md index e84ee991..9457da92 100644 --- a/docs/source/03_01_input_data.md +++ b/docs/source/03_01_input_data.md @@ -36,9 +36,8 @@ where: **NOTE:** -- If rnaExpression is not provided and the tumor type is given in the patient data, expression will be estimated by gene expression in TCGA cohort indicated in the `tumorType` in the patient data (see below). Please, not that this does not work for mouse data. Here, expression imputation is currently not supported. -- If `dnaVariantAlleleFrequency` is given while `rnaVariantAlleleFrequency` is not given, the VAF in RNA will be estimated by the VAF in DNA. -This means that feature scores that rely on the VAF in RNA will be calulated with the VAF in DNA. +- Neofox annotates gene expression in TCGA cohort indicated in the `tumorType` in the patient data (see below) which might be helpful if rnaExpression is unknown. Please, not that this does not work for mouse data. + #### Neoepitope candidates @@ -67,9 +66,7 @@ where: - Neoepitopes with a value for `alleleMhcI` are considered MHC-I neoepitopes, likewise neoepitopes with a value for `isoformMhcII` are considered MHC-II neoepitopes. Both fields cannot be provided for the same neoepitope. - If none of `alleleMhcI` and `isoformMhcII` are provided then the `patientIdentifier` is required and one neoepitope sharing the same sequence will be annotated for each MHC-I allele and MHC-II isoform according to the patient HLA type. -- If the tumor type is given in the patient data (see below), gene expression in the matching TCGA cohort is annotated and expression-related are calculated based on imputated gene expression additionally (see [description of output data](03_02_output_data.md)). Please, note that this does not work for mouse data. Here, expression imputation is currently not supported. -- If `dnaVariantAlleleFrequency` is given while `rnaVariantAlleleFrequency` is not given, the VAF in RNA will be estimated by the VAF in DNA. -This means that feature scores that rely on the VAF in RNA will be calulated with the VAF in DNA. +- Neofox annotates gene expression in TCGA cohort indicated in the `tumorType` in the patient data (see below) which might be helpful if rnaExpression is unknown. Please, not that this does not work for mouse data. ### JSON file format @@ -106,7 +103,7 @@ where: - `identifier`: the patient identifier - `mhcIAlleles`: comma separated MHC I alleles of the patient for HLA-A, HLA-B and HLA-C. If homozygous, the allele should be added twice. - `mhcIIAlleles`: comma separated MHC II alleles of the patient for HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-DPA1 and HLA-DPB1. If homozygous, the allele should be added twice. -- `tumorType`: tumour entity in TCGA study abbreviation format (https://gdc.cancer.gov/resources-tcga-users/tcga-code-tables/tcga-study-abbreviations). This field is required for expression imputation and at the moment the following tumor types are supported: +- `tumorType`: tumour entity in TCGA study abbreviation format (https://gdc.cancer.gov/resources-tcga-users/tcga-code-tables/tcga-study-abbreviations). This field is required for imputation with gene expression and at the moment the following tumor types are supported: | Study Name | Abbreviation | |--------------------------------------------------------------------|-------------------| diff --git a/docs/source/03_02_output_data.md b/docs/source/03_02_output_data.md index 5ec3f023..b90e4e60 100755 --- a/docs/source/03_02_output_data.md +++ b/docs/source/03_02_output_data.md @@ -22,8 +22,10 @@ The following table describes each of the annotations in the output: | imputedGeneExpression | median gene expression in the TCGA cohort of the tumor entity provided in the patient file. | expression | | rnaVariantAlleleFrequency | the variant allele frequency calculated from the RNA | - | | gene | the HGNC gene symbol | - | -| Mutated_rnaExpression | transcript expression normalized by the variant allele frequency of the mutation | expression | -| Mutated_imputedGeneExpression | imputed gene expression normalized by the variant allele frequency of the mutation | | +| Mutated_rnaExpression_fromRNA | transcript expression normalized by the variant allele frequency in RNA of the mutation | expression | +| Mutated_rnaExpression_fromDNA | transcript expression normalized by the variant allele frequency in DNA of the mutation | | +| Mutated_imputedGeneExpression_fromRNA | imputeted gene expression normalized by the variant allele frequency in RNA of the mutation | expression | +| Mutated_imputedGeneExpression_fromDNA | imputed gene expression normalized by the variant allele frequency in RNA of the mutation | | | mutation_not_found_in_proteome | indicates if mutated amino acid sequence was not found in the WT proteome by exact search | Priority score | | NetMHCpan_bestRank_rank | minimal MHC I binding rank score over all neoepitope candidates (8-11mers) and MHC I alleles | MHC I binding with netMHCpan | | NetMHCpan_bestRank_peptide | neoepitope candidate sequence with minimal MHC I binding rank score | MHC I binding with netMHCpan | @@ -98,8 +100,10 @@ The following table describes each of the annotations in the output: | Selfsimilarity_MHCI | score representing the similarity between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptide` | self-similarity | | Selfsimilarity_MHCII | score representing the similarity between `NetMHCIIpan_bestAffinity_peptide` and `NetMHCIIpan_bestAffinity_peptide` | self-similarity | | Number_of_mismatches_MCHI | number of amino acids that do no match between `NetMHCpan_bestRank_peptide` and `NetMHCpan_bestRank_peptideWT` | Priority score | -| Priority_score | combinatorial score of several features such as MHC binding, transcription expression and VAF | Priority score | -| Priority_score_imputed | combinatorial score of several features such as MHC binding, imputed gene expression and VAF | Priority score | +| Priority_score_fromDNA | combinatorial score of several features such as MHC binding, transcription expression and VAF in DNA | Priority score | +| Priority_score_fromRNA | combinatorial score of several features such as MHC binding, transcription expression and VAF in RNA | Priority score | +| Priority_score_imputed_fromDNA | combinatorial score of several features such as MHC binding, imputed gene expression and VAF in DNA | Priority score | +| Priority_score_imputed_fromRNA | combinatorial score of several features such as MHC binding, imputed gene expression and VAF in RNA | Priority score | | Neoag_immunogenicity | output score of neoag model | neoag | | IEDB_Immunogenicity_MHCI | IEDB Immunogenicity score for `NetMHCpan_bestAffinity_peptide` | IEDB Immunogenicity | | IEDB_Immunogenicity_MHCII | IEDB Immunogenicity score for `NetMHCIIpan_bestAffinity_peptide` | IEDB Immunogenicity | @@ -113,8 +117,8 @@ The following table describes each of the annotations in the output: | Dissimilarity_MHCI | score reflecting the dissimilarity of `NetMHCpan_bestAffinity_peptide` to the self-proteome | dissimilarity | | Dissimilarity_MHCII | score reflecting the dissimilarity of `NetMHCIIpan_bestAffinity_peptide` to the self-proteome | dissimilarity | | Vaxrank_bindingScore | total binding score of vaxrank | vaxrank | -| Vaxrank_totalScore | product of total binding score and transcription expression score. Originally, the root of the number of reads supporting the mutation are used in the original implementation. To simplify, the expression normalised to VAF is used. | vaxrank | -| Vaxrank_totalScore_imputed | product of total binding score and imputed gene expression score. Originally, the root of the number of reads supporting the mutation are used in the original implementation. To simplify, the expression normalised to VAF is used. | vaxrank | +| Vaxrank_totalScore | product of total binding score and transcription expression score. Originally, the root of the number of reads supporting the mutation are used in the original implementation. To simplify, the transcript expression normalised to VAF is used. | vaxrank | +| Vaxrank_totalScore_imputed | product of total binding score and imputed gene expression score. Originally, the root of the number of reads supporting the mutation are used in the original implementation. To simplify, the imputed gene expression normalised to VAF is used. | vaxrank | | PRIME_bestScore_allele | best predicted MHC allele by PRIME model | PRIME | | PRIME_bestScore_peptide | best predicted neoepitope candidate by PRIME model | PRIME | | PRIME_bestScore_rank | output rank score of PRIME model | PRIME | @@ -282,7 +286,7 @@ the MHC-II neoepitope candidates. Two output files with the suffix "*_mhcI_epitope_candidates_annotated.tsv" and ""*_mhcII_epitope_candidates_annotated.tsv"" are created. -The following table describes each of the annotations in the output: +The following table describes each of the annotations in the output. MHC-I or MHC-II specific features will be only available in the respective table: **TABLE 2** @@ -298,6 +302,10 @@ The following table describes each of the annotations in the output: | imputedGeneExpression | median gene expression in the TCGA cohort of the tumor entity provided in the patient file. | expression | | rnaVariantAlleleFrequency | the variant allele frequency calculated from the RNA | - | | gene | the HGNC gene symbol | - | +| Mutated_rnaExpression_fromRNA | transcript expression normalized by the variant allele frequency in RNA of the mutation | expression | +| Mutated_rnaExpression_fromDNA | transcript expression normalized by the variant allele frequency in DNA of the mutation | | +| Mutated_imputedGeneExpression_fromRNA | imputeted gene expression normalized by the variant allele frequency in RNA of the mutation | expression | +| Mutated_imputedGeneExpression_fromDNA | imputed gene expression normalized by the variant allele frequency in RNA of the mutation | | | affinityMutated | NetMHCpan / NetMHCIIpan affinity score of the mutated peptide for MHC-I or MHC-II neoepitopes respectively | MHC-I / MHC-II binding with netMHCpan / netMHCIIpan | | affinityWildType | NetMHCpan / NetMHCIIpan affinity score of the wild type peptide for MHC-I or MHC-II neoepitopes respectively | MHC-I / MHC-II binding with netMHCpan / netMHCIIpan | | rankMutated | NetMHCpan / NetMHCIIpan rank of the mutated peptide for MHC-I or MHC-II neoepitopes respectively | MHC-I / MHC-II binding with netMHCpan / netMHCIIpan | @@ -315,14 +323,17 @@ The following table describes each of the annotations in the output: | PRIME_WT_score | PRIME score of the wild type peptide for MHC-I neoepitopes | MHC-I binding with PRIME | | PRIME_WT_rank | PRIME rank of the wild type peptide for MHC-I neoepitopes | MHC-I binding with PRIME | | DAI | difference of `affinityWildType` and `affinityMutated` | DAI (only availble for MHC-I) | -| Gl | | Length of the deletion (in the core), if any. | MHC-I / MHC-II binding with netMHCpan / netMHCIIpan -| Gp | | Position of the deletion (in the core), if any. | MHC-I / MHC-II binding with netMHCpan / netMHCIIpan -| Icore | | Interaction core. This is the sequence of the binding core including eventual insertions of deletions. | MHC-I / MHC-II binding with netMHCpan / netMHCIIpan -| Of | | The starting position of the Core within the predicted peptide | MHC-I / MHC-II binding with netMHCpan / netMHCIIpan -| Core_Rel | | Reliability of the (MHCII) binding core, expressed as the fraction of networks in the ensemble selecting the optimal core | MHC-I / MHC-II binding with netMHCpan / netMHCIIpan +| Gl | Length of the deletion (in the core), if any. | MHC-I / MHC-II binding with netMHCpan / netMHCIIpan +| Gp | Position of the deletion (in the core), if any. | MHC-I / MHC-II binding with netMHCpan / netMHCIIpan +| Icore | Interaction core. This is the sequence of the binding core including eventual insertions of deletions. | MHC-I / MHC-II binding with netMHCpan / netMHCIIpan +| Of | The starting position of the Core within the predicted peptide | MHC-I / MHC-II binding with netMHCpan / netMHCIIpan +| Core_Rel | Reliability of the (MHCII) binding core, expressed as the fraction of networks in the ensemble selecting the optimal core | MHC-I / MHC-II binding with netMHCpan / netMHCIIpan | IEDB_Immunogenicity | IEDB Immunogenicity score for `affinityMutated` | IEDB immunogenicity | | Improved_Binder_MHCI | ratio of `affinityWildType` and `affinityMutated` > 1.2 | self-similarity (only available for MHC-I) | -| Priority_score | combinatorial score of several features such as MHC binding, expression and VAF | Priority score | +| Priority_score_fromDNA | combinatorial score of several features such as MHC binding, transcription expression and VAF in DNA | Priority score | +| Priority_score_fromRNA | combinatorial score of several features such as MHC binding, transcription expression and VAF in RNA | Priority score | +| Priority_score_imputed_fromDNA | combinatorial score of several features such as MHC binding, imputed gene expression and VAF in DNA | Priority score | +| Priority_score_imputed_fromRNA | combinatorial score of several features such as MHC binding, imputed gene expression and VAF in RNA | Priority score | | mutation_not_found_in_proteome | indicates if mutated amino acid sequence was not found in the WT proteome by exact search | Priority score | | Selfsimilarity | score representing the similarity between `rankMutated` and `rankWildType` | self-similarity | | Selfsimilarity_conserved_binder | score representing the similarity between `rankMutated` and `rankWildType` for conserved binder only | self-similarity (only available for MHC-I) | diff --git a/docs/source/03_03_usage.md b/docs/source/03_03_usage.md index c749d875..6f4a4a4a 100755 --- a/docs/source/03_03_usage.md +++ b/docs/source/03_03_usage.md @@ -54,12 +54,12 @@ The optional **config** file with the paths to the dependencies can look like th ````commandline NEOFOX_REFERENCE_FOLDER=path/to/reference/folder NEOFOX_RSCRIPT=`which Rscript` -NEOFOX_BLASTP=path/to/ncbi-blast-2.10.1+/bin/blastp -NEOFOX_NETMHCPAN=path/to/netMHCpan-4.1/netMHCpan -NEOFOX_NETMHC2PAN=path/to/netMHCIIpan-4.0/netMHCIIpan -NEOFOX_MIXMHCPRED=path/to/MixMHCpred-2.1/MixMHCpred -NEOFOX_MIXMHC2PRED=path/to/MixMHC2pred-1.2/MixMHC2pred_unix -NEOFOX_MAKEBLASTDB=path/to/ncbi-blast-2.8.1+/bin/makeblastdb +NEOFOX_BLASTP=path/to/blast/bin/blastp +NEOFOX_NETMHCPAN=path/to/netMHCpan/netMHCpan +NEOFOX_NETMHC2PAN=path/to/netMHCIIpan/netMHCIIpan +NEOFOX_MIXMHCPRED=path/to/MixMHCpred/MixMHCpred +NEOFOX_MIXMHC2PRED=path/to/MixMHC2pred/MixMHC2pred_unix +NEOFOX_MAKEBLASTDB=path/to/ncbi-blast/bin/makeblastdb NEOFOX_PRIME=/path/to/PRIME/PRIME ```` @@ -89,6 +89,9 @@ where: ## Running from docker +**NOTE: The provided docker recipe is not adapted to Neofox-v1.1.0. Please, use a previous version at the moment if running from docker is required. +The docker recipe will be updated soon.** + In order to run the command line in a docker image, all of the above applies but some additional steps are required. From 1f61315fc73a9a77ff14b4b31f118ba62410f338 Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Fri, 22 Sep 2023 10:38:39 +0200 Subject: [PATCH 71/83] Added protocol to mouse MixMHC2pred PWMdef URL --- neofox/references/installer.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/neofox/references/installer.py b/neofox/references/installer.py index cd97fbc1..e63ccd71 100644 --- a/neofox/references/installer.py +++ b/neofox/references/installer.py @@ -42,7 +42,7 @@ IEDB_URL = 'http://www.iedb.org/downloader.php?file_name=doc/tcell_full_v3.zip' -MIXMHC2PRED_PWM_MOUSE_URL = "ec2-18-188-210-66.us-east-2.compute.amazonaws.com:4000/data/PWMdef/PWMdef_Mouse.zip" +MIXMHC2PRED_PWM_MOUSE_URL = "http://ec2-18-188-210-66.us-east-2.compute.amazonaws.com:4000/data/PWMdef/PWMdef_Mouse.zip" class NeofoxReferenceInstaller(object): From 99daa7f4782f9273a78049be11f65bc5dc7068a8 Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Fri, 22 Sep 2023 14:40:51 +0200 Subject: [PATCH 72/83] Added and adapted MixMHC2pred tests for mouse --- .../integration_test_tools.py | 7 + .../integration_tests/test_mixmhcpred.py | 3 +- .../test_mixmhcpred_mouse.py | 121 ++++++++++++++++++ 3 files changed, 130 insertions(+), 1 deletion(-) create mode 100755 neofox/tests/integration_tests/test_mixmhcpred_mouse.py diff --git a/neofox/tests/integration_tests/integration_test_tools.py b/neofox/tests/integration_tests/integration_test_tools.py index 3d44baf5..801ee53a 100755 --- a/neofox/tests/integration_tests/integration_test_tools.py +++ b/neofox/tests/integration_tests/integration_test_tools.py @@ -99,6 +99,13 @@ def get_h2_two_test(h2_database): ], h2_database ) +def get_h2_two_test_b(h2_database): + return MhcFactory.build_mhc2_alleles( + [ + "H2Ab", + "H2Ab", + ], h2_database + ) mutations_with_rare_aminoacids = [ ("UTTDSDGKF", "UTTDSWGKF"), # this is an epitope from IEDB of length 9 diff --git a/neofox/tests/integration_tests/test_mixmhcpred.py b/neofox/tests/integration_tests/test_mixmhcpred.py index 3b147bfb..7a3cabd5 100755 --- a/neofox/tests/integration_tests/test_mixmhcpred.py +++ b/neofox/tests/integration_tests/test_mixmhcpred.py @@ -40,7 +40,8 @@ def setUp(self): runner=self.runner, configuration=self.configuration, mhc_parser=mhc_parser ) self.mixmhc2pred = MixMHC2pred( - runner=self.runner, configuration=self.configuration, mhc_parser=mhc_parser + runner=self.runner, configuration=self.configuration, mhc_parser=mhc_parser, + references=self.references ) self.hla_database = self.references.get_mhc_database() self.test_mhc_one = integration_test_tools.get_hla_one_test(self.hla_database) diff --git a/neofox/tests/integration_tests/test_mixmhcpred_mouse.py b/neofox/tests/integration_tests/test_mixmhcpred_mouse.py new file mode 100755 index 00000000..7cbf7620 --- /dev/null +++ b/neofox/tests/integration_tests/test_mixmhcpred_mouse.py @@ -0,0 +1,121 @@ +# +# Copyright (c) 2020-2030 Translational Oncology at the Medical Center of the Johannes Gutenberg-University Mainz gGmbH. +# +# This file is part of Neofox +# (see https://github.com/tron-bioinformatics/neofox). +# +# This program is free software: you can redistribute it and/or modify +# it under the terms of the GNU General Public License as published by +# the Free Software Foundation, either version 3 of the License, or +# (at your option) any later version. +# +# This program is distributed in the hope that it will be useful, +# but WITHOUT ANY WARRANTY; without even the implied warranty of +# MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the +# GNU General Public License for more details. +# +# You should have received a copy of the GNU General Public License +# along with this program. If not, see .# +from unittest import TestCase +from logzero import logger + +from neofox.model.factories import MhcFactory +from neofox.model.mhc_parser import MhcParser +from neofox.model.neoantigen import Mhc2Name +from neofox.helpers.epitope_helper import EpitopeHelper +import neofox.tests.integration_tests.integration_test_tools as integration_test_tools +from neofox.MHC_predictors.MixMHCpred.mixmhc2pred import MixMHC2pred +from neofox.helpers.runner import Runner +from neofox.annotation_resources.uniprot.uniprot import Uniprot +from neofox.tests.tools import get_neoantigen +from neofox.references.references import ReferenceFolder, DependenciesConfiguration, ORGANISM_HOMO_SAPIENS, \ + ORGANISM_MUS_MUSCULUS + + +class TestMixMHCPredMouse(TestCase): + def setUp(self): + self.references, self.configuration = integration_test_tools.load_references(organism=ORGANISM_MUS_MUSCULUS) + self.runner = Runner() + mhc_parser = MhcParser.get_mhc_parser(self.references.get_mhc_database()) + #self.mixmhcpred = MixMHCpred( + # runner=self.runner, configuration=self.configuration, mhc_parser=mhc_parser + #) + self.mixmhc2pred = MixMHC2pred( + runner=self.runner, configuration=self.configuration, mhc_parser=mhc_parser, + references=self.references + ) + self.hla_database = self.references.get_mhc_database() + #self.test_mhc_one = integration_test_tools.get_hla_one_test(self.hla_database) + self.test_mhc_two = integration_test_tools.get_h2_two_test(self.hla_database) + self.test_mhc_two_b = integration_test_tools.get_h2_two_test_b(self.hla_database) + self.uniprot = Uniprot(self.references.uniprot_pickle) + + def test_mixmhcpred2_epitope_iedb_b_haplotype(self): + # Test mixmhc2pred with H2Ab allele (C57BL/6 setting) + # this is an antigen from IEDB of length 27 + neoantigen = get_neoantigen( + mutated_xmer="RQHSIKEGLQFIQPPLSYPGTQEQYAV", + wild_type_xmer= "RQHSIKEGLQFIQSPLSYPGTQEQYAV") + self.mixmhc2pred.run( + neoantigen=neoantigen, mhc=self.test_mhc_two_b, + uniprot=self.uniprot + ) + + best_result = EpitopeHelper.select_best_by_rank(predictions=self.mixmhc2pred.results) + + self.assertEquals("QPPLSYPGTQEQYAV", best_result.mutated_peptide) + self.assertEquals(9.43, best_result.rank_mutated) + self.assertEquals("H2Ab", best_result.isoform_mhc_i_i.name) + + def test_mixmhcpred2_epitope_iedb(self): + # Test mixmhc2pred with H2Ad and H2Ed allele (BALB/c setting) + # this is an antigen from IEDB of length 27 + neoantigen = get_neoantigen( + mutated_xmer="RQHSIKEGLQFIQPPLSYPGTQEQYAV", + wild_type_xmer= "RQHSIKEGLQFIQSPLSYPGTQEQYAV") + self.mixmhc2pred.run( + neoantigen=neoantigen, mhc=self.test_mhc_two, + uniprot=self.uniprot + ) + + best_result = EpitopeHelper.select_best_by_rank(predictions=self.mixmhc2pred.results) + + self.assertEquals("KEGLQFIQPPLSYPG", best_result.mutated_peptide) + self.assertEquals(11.9, best_result.rank_mutated) + self.assertEquals("H2Ad", best_result.isoform_mhc_i_i.name) + + def test_mixmhcpred2_no_mutation(self): + neoantigen = get_neoantigen( + mutated_xmer="RQHSIKEGLQFIQSPLSYPGTQEQYAV", + wild_type_xmer= "RQHSIKEGLQFIQSPLSYPGTQEQYAV") + self.mixmhc2pred.run( + neoantigen=neoantigen, mhc=self.test_mhc_two, + uniprot=self.uniprot + ) + + best_result = EpitopeHelper.select_best_by_rank(predictions=self.mixmhc2pred.results) + + self.assertIsNone(best_result.mutated_peptide) + self.assertIsNone(best_result.rank_mutated) + self.assertIsNone(best_result.isoform_mhc_i_i.name) + + def test_mixmhc2pred_allele(self): + + neoantigen = get_neoantigen(mutated_xmer="RQHSIKEGLQFIQPPLSYPGTQEQYAV", wild_type_xmer="RQHSIKEGLQFIQSPLSYPGTQEQYAV") + # this is a MHC II genotype which results in no available alleles for MixMHC2pred + MHC_TWO_NEW = MhcFactory.build_mhc2_alleles( + [ + "H2Ab", + "H2Ad", + "H2Ed" + ], + self.hla_database + ) + alleles = self.mixmhc2pred.transform_h2_alleles_for_prediction(MHC_TWO_NEW) + logger.info(alleles) + self.assertListEqual(alleles, ['H2_Aa_b__H2_Ab_b', 'H2_Aa_d__H2_Ab_d', 'H2_Ea_d__H2_Eb_d']) + self.mixmhc2pred.run(neoantigen=neoantigen, mhc=MHC_TWO_NEW, uniprot=self.uniprot) + best_result = EpitopeHelper.select_best_by_rank(predictions=self.mixmhc2pred.results) + self.assertIsNotNone(best_result.mutated_peptide) + self.assertIsNotNone(best_result.rank_mutated) + self.assertIsNotNone(best_result.isoform_mhc_i_i.name) From 7a83b7ebb0829e2b076b80f8b0199433ca291efb Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Fri, 22 Sep 2023 17:49:29 +0200 Subject: [PATCH 73/83] Adapted mixmhc2pred command line list to work also in human mode. Adapted mixmhc2mouse pred to the supported alleles --- neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py | 11 ++++------- .../tests/integration_tests/test_mixmhcpred_mouse.py | 7 ++++--- 2 files changed, 8 insertions(+), 10 deletions(-) diff --git a/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py b/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py index 70532d59..15feadaf 100755 --- a/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py +++ b/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py @@ -198,15 +198,9 @@ def _parse_mixmhc2pred_output(self, filename: str) -> List[PredictedEpitope]: return parsed_results def _mixmhc2prediction(self, isoforms: List[str], potential_ligand_sequences: List[str]) -> List[PredictedEpitope]: - # TODO: define the pwm_path again because the mouse path is only defined by the config tmptxt = intermediate_files.create_temp_mixmhc2pred(potential_ligand_sequences, prefix="tmp_sequence_") outtmp = intermediate_files.create_temp_file(prefix="mixmhc2pred", suffix=".txt") - if self.organism == ORGANISM_HOMO_SAPIENS: - pwm_argument = "" - else: - pwm_dir = self.references.mixmhc2pred_pwm_dir - pwm_argument = f"-f {pwm_dir}" cmd = [ self.configuration.mix_mhc2_pred, "-a", @@ -215,9 +209,12 @@ def _mixmhc2prediction(self, isoforms: List[str], potential_ligand_sequences: Li tmptxt, "-o", outtmp, - pwm_argument, "--no_context" ] + if self.organism != ORGANISM_HOMO_SAPIENS: + pwm_dir = self.references.mixmhc2pred_pwm_dir + cmd.extend(["-f", pwm_dir]) + self.runner.run_command(cmd) results = self._parse_mixmhc2pred_output(filename=outtmp) os.remove(outtmp) diff --git a/neofox/tests/integration_tests/test_mixmhcpred_mouse.py b/neofox/tests/integration_tests/test_mixmhcpred_mouse.py index 7cbf7620..8f9bd029 100755 --- a/neofox/tests/integration_tests/test_mixmhcpred_mouse.py +++ b/neofox/tests/integration_tests/test_mixmhcpred_mouse.py @@ -50,7 +50,7 @@ def setUp(self): self.test_mhc_two_b = integration_test_tools.get_h2_two_test_b(self.hla_database) self.uniprot = Uniprot(self.references.uniprot_pickle) - def test_mixmhcpred2_epitope_iedb_b_haplotype(self): + def test_mixmhcpred2_antigen_iedb_b_haplotype(self): # Test mixmhc2pred with H2Ab allele (C57BL/6 setting) # this is an antigen from IEDB of length 27 neoantigen = get_neoantigen( @@ -67,7 +67,7 @@ def test_mixmhcpred2_epitope_iedb_b_haplotype(self): self.assertEquals(9.43, best_result.rank_mutated) self.assertEquals("H2Ab", best_result.isoform_mhc_i_i.name) - def test_mixmhcpred2_epitope_iedb(self): + def test_mixmhcpred2_antigen_iedb(self): # Test mixmhc2pred with H2Ad and H2Ed allele (BALB/c setting) # this is an antigen from IEDB of length 27 neoantigen = get_neoantigen( @@ -100,7 +100,6 @@ def test_mixmhcpred2_no_mutation(self): self.assertIsNone(best_result.isoform_mhc_i_i.name) def test_mixmhc2pred_allele(self): - neoantigen = get_neoantigen(mutated_xmer="RQHSIKEGLQFIQPPLSYPGTQEQYAV", wild_type_xmer="RQHSIKEGLQFIQSPLSYPGTQEQYAV") # this is a MHC II genotype which results in no available alleles for MixMHC2pred MHC_TWO_NEW = MhcFactory.build_mhc2_alleles( @@ -108,6 +107,8 @@ def test_mixmhc2pred_allele(self): "H2Ab", "H2Ad", "H2Ed" + # this mouse allele is supported by MixMHC2pred but does not exist in H2 database + #"H2Anb1" ], self.hla_database ) From 269fa854be1e4076c8eaf319158773b217e78b8f Mon Sep 17 00:00:00 2001 From: Franziska Lang Date: Mon, 25 Sep 2023 09:39:25 +0200 Subject: [PATCH 74/83] fix installer --- neofox/references/installer.py | 7 +++---- 1 file changed, 3 insertions(+), 4 deletions(-) diff --git a/neofox/references/installer.py b/neofox/references/installer.py index e63ccd71..77a90c87 100644 --- a/neofox/references/installer.py +++ b/neofox/references/installer.py @@ -69,6 +69,7 @@ def install(self): self._install_r_dependencies() else: logger.warning("R dependencies will need to be installed manually") + mixmhc2pred_resources = [] if self.install_mouse_mixmhc2pred: mixmhc2pred_resources = self._set_mixmhc2pred_pwms() else: @@ -96,8 +97,8 @@ def _save_resources_versions( resources_version = [ Resource(name="netMHCpan", version="4.1"), Resource(name="netMHCIIpan", version="4.0"), - Resource(name="mixMHCpred", version="2.1"), - Resource(name="mixMHC2pred", version="1.2"), + Resource(name="mixMHCpred", version="2.2"), + Resource(name="mixMHC2pred", version="2.0.2"), iedb_resource, hla_resource ] + proteome_resources + mixmhc2pred_resources @@ -253,8 +254,6 @@ def _set_proteome(self): url=MOUSE_PROTEOME_ISOFORMS, hash=hash_isoforms_mouse), ] - return hash_human, hash_isoforms_human, version_human, hash_mouse, hash_isoforms_mouse, version_mouse - def _prepare_proteome(self, url, url_isoforms, version_url, proteome_file_name, proteome_prefix, proteome_pickle_file_name): # download proteome hash = self._download_and_unzip(proteome_file_name, url) From 3111942999e0820e775ae2de62347dca1650e794 Mon Sep 17 00:00:00 2001 From: Franziska Lang Date: Mon, 25 Sep 2023 10:39:01 +0200 Subject: [PATCH 75/83] fix mixmhc2pred --- .../annotator/neoepitope_mhc_binding_annotator.py | 2 +- .../integration_tests/integration_test_tools.py | 9 +-------- .../integration_tests/test_neoepitope_annotator.py | 13 +++++++++---- 3 files changed, 11 insertions(+), 13 deletions(-) diff --git a/neofox/annotator/neoepitope_mhc_binding_annotator.py b/neofox/annotator/neoepitope_mhc_binding_annotator.py index 684484ef..dcbfd273 100644 --- a/neofox/annotator/neoepitope_mhc_binding_annotator.py +++ b/neofox/annotator/neoepitope_mhc_binding_annotator.py @@ -40,7 +40,7 @@ def __init__(self, references: ReferenceFolder, configuration: DependenciesConfi runner=self.runner, configuration=configuration, mhc_parser=self.mhc_parser, blastp_runner=self.proteome_blastp_runner) self.mixmhcpred = MixMHCpred(self.runner, self.configuration, self.mhc_parser) - self.mixmhc2pred = MixMHC2pred(self.runner, self.configuration, self.mhc_parser) + self.mixmhc2pred = MixMHC2pred(self.runner, self.configuration, self.mhc_parser, references) self.prime = Prime(self.runner, self.configuration, self.mhc_parser) def get_mhc_binding_annotations(self, neoepitope: PredictedEpitope) -> PredictedEpitope: diff --git a/neofox/tests/integration_tests/integration_test_tools.py b/neofox/tests/integration_tests/integration_test_tools.py index 801ee53a..49762e7c 100755 --- a/neofox/tests/integration_tests/integration_test_tools.py +++ b/neofox/tests/integration_tests/integration_test_tools.py @@ -99,13 +99,6 @@ def get_h2_two_test(h2_database): ], h2_database ) -def get_h2_two_test_b(h2_database): - return MhcFactory.build_mhc2_alleles( - [ - "H2Ab", - "H2Ab", - ], h2_database - ) mutations_with_rare_aminoacids = [ ("UTTDSDGKF", "UTTDSWGKF"), # this is an epitope from IEDB of length 9 @@ -203,7 +196,7 @@ def assert_neoepitope_mhci(self, original_neoepitope: PredictedEpitope, annotate self.assert_annotation(annotated_neoepitope, annotation_name="hex_alignment_score") # others to comes - self.assert_annotation(annotated_neoepitope, annotation_name="Priority_score") + self.assert_annotation(annotated_neoepitope, annotation_name="Priority_score_fromDNA") self.assert_annotation(annotated_neoepitope, annotation_name="Tcell_predictor") def assert_neoepitope_mhcii(self, original_neoepitope: PredictedEpitope, annotated_neoepitope: PredictedEpitope): diff --git a/neofox/tests/integration_tests/test_neoepitope_annotator.py b/neofox/tests/integration_tests/test_neoepitope_annotator.py index f5954344..01f0c10e 100644 --- a/neofox/tests/integration_tests/test_neoepitope_annotator.py +++ b/neofox/tests/integration_tests/test_neoepitope_annotator.py @@ -61,7 +61,7 @@ def test_neoepitope_mhci_9mer_with_frequencies_and_gene(self): annotated_neoepitope = self.annotator.get_annotated_neoepitope(neoepitope=neoepitope) self.assert_neoepitope_mhci(original_neoepitope=neoepitope, annotated_neoepitope=annotated_neoepitope) - self.assert_float_annotation(annotated_neoepitope, annotation_name="Priority_score") + self.assert_float_annotation(annotated_neoepitope, annotation_name="Priority_score_fromDNA") self.assert_float_annotation(annotated_neoepitope, annotation_name="Tcell_predictor") def test_neoepitope_mhci_10mer_no_tcell_predictor(self): @@ -98,6 +98,7 @@ def test_neoepitope_mhci_without_dna_vaf(self): mutated_peptide="DILVTDQTR", wild_type_peptide="DILVIDQTR", allele_mhc_i=self._get_test_mhci_allele('HLA-A*01:01'), + dna_variant_allele_frequency=None, rna_variant_allele_frequency=0.1, rna_expression=125, gene='BRCA2' @@ -107,15 +108,19 @@ def test_neoepitope_mhci_without_dna_vaf(self): self.assert_neoepitope_mhci(original_neoepitope=neoepitope_with_dna_vaf, annotated_neoepitope=annotated_neoepitope1) + print(neoepitope_with_dna_vaf) + annotated_neoepitope2 = self.annotator.get_annotated_neoepitope(neoepitope=neoepitope_without_dna_vaf) self.assert_neoepitope_mhci(original_neoepitope=neoepitope_without_dna_vaf, annotated_neoepitope=annotated_neoepitope2) + print(annotated_neoepitope2) + self.assertNotEqual( EpitopeHelper.get_annotation_by_name( - annotated_neoepitope1.neofox_annotations.annotations, "Priority_score"), + annotated_neoepitope1.neofox_annotations.annotations, "Priority_score_fromDNA"), EpitopeHelper.get_annotation_by_name( - annotated_neoepitope2.neofox_annotations.annotations, "Priority_score") + annotated_neoepitope2.neofox_annotations.annotations, "Priority_score_fromDNA") ) def test_neoepitope_mhci_without_vaf(self): @@ -137,7 +142,7 @@ def test_neoepitope_mhci_without_vaf(self): self.assertEqual( EpitopeHelper.get_annotation_by_name( - annotated_neoepitope.neofox_annotations.annotations, "Priority_score"), "NA") + annotated_neoepitope.neofox_annotations.annotations, "Priority_score_fromDNA"), "NA") def test_neoepitope_mhcii_annotation(self): From 57ef83c6cc4f9f6bc5e4d4a9cefb9c6e88af4276 Mon Sep 17 00:00:00 2001 From: Franziska Lang Date: Mon, 25 Sep 2023 10:47:09 +0200 Subject: [PATCH 76/83] update docs --- docs/source/02_installation.md | 6 ++++-- 1 file changed, 4 insertions(+), 2 deletions(-) diff --git a/docs/source/02_installation.md b/docs/source/02_installation.md index b63063c5..35f48982 100755 --- a/docs/source/02_installation.md +++ b/docs/source/02_installation.md @@ -56,7 +56,7 @@ conda install bioconda::neofox ### Install third-party dependencies -Please, check the licences of third-party dependencies. +**NOTE**: Please, check the licences of third-party dependencies. #### Install R @@ -191,7 +191,7 @@ export NEOFOX_HLA_DATABASE=https://raw.githubusercontent.com/ANHIG/IMGTHLA/Lates Run the following to configure the NeoFox reference folder: ``` -neofox-configure --reference-folder /your/neofox/folder [--install-r-dependencies] +neofox-configure --reference-folder /your/neofox/folder [--install-r-dependencies --install_mouse_mixmhc2pred] ``` **NOTE**: when installing from conda `--install-r-dependencies` is not needed. @@ -199,6 +199,8 @@ neofox-configure --reference-folder /your/neofox/folder [--install-r-dependencie The above command will install several resources and store in the annotations metadata their version, MD5 checksum and download timestamp. +To run NeoFox on data from mouse with MixMHC2pred, mouse-specific PMWs are required. For such use cases the reference folder needs to be configured with `--install_mouse_mixmhc2pred` (see also ) + Unless indicated to the installer by flag `--install-r-dependencies` you will need to install manually some R packages. These packages are the following: ``` lattice From e35075ac703a3e1ae343d2306de881641f793b6d Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Mon, 25 Sep 2023 13:26:37 +0200 Subject: [PATCH 77/83] Removed print command --- neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py | 1 - 1 file changed, 1 deletion(-) diff --git a/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py b/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py index 15feadaf..dbcca511 100755 --- a/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py +++ b/neofox/MHC_predictors/MixMHCpred/mixmhc2pred.py @@ -244,7 +244,6 @@ def run(self, mhc: List[Mhc2], neoantigen: Neoantigen, uniprot): isoforms=mhc2_alleles, potential_ligand_sequences=potential_ligand_sequences) else: logger.warning("None of the MHC II alleles are supported by MixMHC2pred") - print(mhc2_alleles) def run_peptide(self, peptide: str, isoform: Mhc2Isoform) -> PredictedEpitope: """ From 3cdb11690920bc6f1efa27576da515a8ff3cf6bf Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Mon, 25 Sep 2023 13:34:27 +0200 Subject: [PATCH 78/83] Added get_h2_two_test_b function for testing mixmhc2pred --- neofox/tests/integration_tests/integration_test_tools.py | 7 +++++++ 1 file changed, 7 insertions(+) diff --git a/neofox/tests/integration_tests/integration_test_tools.py b/neofox/tests/integration_tests/integration_test_tools.py index 49762e7c..53c60695 100755 --- a/neofox/tests/integration_tests/integration_test_tools.py +++ b/neofox/tests/integration_tests/integration_test_tools.py @@ -99,6 +99,13 @@ def get_h2_two_test(h2_database): ], h2_database ) +def get_h2_two_test_b(h2_database): + return MhcFactory.build_mhc2_alleles( + [ + "H2Ab", + "H2Ab", + ], h2_database + ) mutations_with_rare_aminoacids = [ ("UTTDSDGKF", "UTTDSWGKF"), # this is an epitope from IEDB of length 9 From 737a0d0edd9f2acef68b2b2a86226fb7bc98e563 Mon Sep 17 00:00:00 2001 From: Luis Kress Date: Tue, 26 Sep 2023 14:24:33 +0200 Subject: [PATCH 79/83] Fixed bug in test_generator_rate where pair predictions for mhci was used instead of mhcii. --- neofox/tests/integration_tests/test_best_multiple_binder.py | 4 ++-- 1 file changed, 2 insertions(+), 2 deletions(-) diff --git a/neofox/tests/integration_tests/test_best_multiple_binder.py b/neofox/tests/integration_tests/test_best_multiple_binder.py index d9e6693b..99c0b235 100755 --- a/neofox/tests/integration_tests/test_best_multiple_binder.py +++ b/neofox/tests/integration_tests/test_best_multiple_binder.py @@ -341,10 +341,10 @@ def test_generator_rate_mhcII(self): position_of_mutation=mutation.position, predictions=predictions_wt ) - paired_predictions = EpitopeHelper.pair_predictions( + paired_predictions = EpitopeHelper.pair_mhcii_predictions( predictions=predicted_neoepitopes, predictions_wt=filtered_predictions_wt) generator_rate_ADN = best_multiple.determine_number_of_alternative_binders(predictions=paired_predictions) generator_rate_CDN = best_multiple.determine_number_of_binders(predictions=paired_predictions) - self.assertEqual(generator_rate_ADN, 6) + self.assertEqual(generator_rate_ADN, 0) self.assertEqual(generator_rate_CDN, 0) From ed5cd0fd626e9bf176e820aae5f763c8c74f92ca Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Thu, 5 Oct 2023 16:09:43 +0200 Subject: [PATCH 80/83] remove NeoAg in annotator and integration_tests --- MANIFEST.in | 1 - neofox/__init__.py | 2 +- neofox/annotator/neoantigen_annotator.py | 11 +- neofox/annotator/neoepitope_annotator.py | 2 - neofox/published_features/neoag/__init__.py | 18 ---- .../neoag/neoag-master/Final_gbm_model.rds | Bin 1859034 -> 0 bytes .../neoag/neoag-master/LICENSE.txt | 16 --- .../NeoAg_immunogenicity_predicition_GBM.R | 75 -------------- .../neoag/neoag_gbm_model.py | 98 ------------------ neofox/tests/integration_tests/test_neoag.py | 66 ------------ neofox/tests/integration_tests/test_neofox.py | 4 +- 11 files changed, 4 insertions(+), 289 deletions(-) delete mode 100755 neofox/published_features/neoag/__init__.py delete mode 100755 neofox/published_features/neoag/neoag-master/Final_gbm_model.rds delete mode 100755 neofox/published_features/neoag/neoag-master/LICENSE.txt delete mode 100755 neofox/published_features/neoag/neoag-master/NeoAg_immunogenicity_predicition_GBM.R delete mode 100755 neofox/published_features/neoag/neoag_gbm_model.py delete mode 100755 neofox/tests/integration_tests/test_neoag.py diff --git a/MANIFEST.in b/MANIFEST.in index 0da8967c..c010435d 100755 --- a/MANIFEST.in +++ b/MANIFEST.in @@ -1,4 +1,3 @@ -include neofox/published_features/neoag/neoag-master/* include neofox/published_features/self_similarity/BLOSUM62-2.matrix.txt include neofox/published_features/Tcell_predictor/amino-acids-features.pickle include neofox/published_features/Tcell_predictor/genes-expression.pickle diff --git a/neofox/__init__.py b/neofox/__init__.py index de59c270..fd361f58 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b28" +VERSION = "1.1.0b29" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP" diff --git a/neofox/annotator/neoantigen_annotator.py b/neofox/annotator/neoantigen_annotator.py index 7325a0a6..d63fa6d5 100755 --- a/neofox/annotator/neoantigen_annotator.py +++ b/neofox/annotator/neoantigen_annotator.py @@ -31,7 +31,6 @@ from neofox.model.factories import AnnotationFactory from neofox.model.mhc_parser import MhcParser from neofox.published_features.Tcell_predictor.tcellpredictor_wrapper import TcellPrediction -from neofox.published_features.neoag.neoag_gbm_model import NeoagCalculator from neofox.published_features.self_similarity.self_similarity import SelfSimilarityCalculator from neofox.published_features.expression import Expression from neofox.model.neoantigen import Patient, Neoantigen, Annotations, PredictedEpitope @@ -57,7 +56,7 @@ def __init__(self, references: ReferenceFolder, configuration: DependenciesConfi self.rank_mhcii_threshold = rank_mhcii_threshold # NOTE: these resources do not read any file thus can be initialised fast - self.neoag_calculator = NeoagCalculator(runner=self.runner, configuration=configuration) + #self.neoag_calculator = NeoagCalculator(runner=self.runner, configuration=configuration) self.expression_calculator = Expression() self.mhc_database = references.get_mhc_database() self.mhc_parser = MhcParser.get_mhc_parser(self.mhc_database) @@ -193,14 +192,6 @@ def get_annotated_neoantigen(self, neoantigen: Neoantigen, patient: Patient, wit ) ) - # neoag immunogenicity model - if netmhcpan and netmhcpan.best_epitope_by_affinity: - neoantigen.neofox_annotations.annotations.append( - self.neoag_calculator.get_annotation( - epitope_mhci=netmhcpan.best_epitope_by_affinity, - neoantigen=neoantigen) - ) - # IEDB immunogenicity if self.organism == ORGANISM_HOMO_SAPIENS: neoantigen.neofox_annotations.annotations.extend( diff --git a/neofox/annotator/neoepitope_annotator.py b/neofox/annotator/neoepitope_annotator.py index 32f7602c..091c113e 100755 --- a/neofox/annotator/neoepitope_annotator.py +++ b/neofox/annotator/neoepitope_annotator.py @@ -32,7 +32,6 @@ from neofox.model.factories import AnnotationFactory from neofox.model.mhc_parser import MhcParser from neofox.published_features.Tcell_predictor.tcellpredictor_wrapper import TcellPrediction -from neofox.published_features.neoag.neoag_gbm_model import NeoagCalculator from neofox.published_features.self_similarity.self_similarity import SelfSimilarityCalculator from neofox.published_features.expression import Expression from neofox.model.neoantigen import Patient, Neoantigen, Annotations, PredictedEpitope @@ -54,7 +53,6 @@ def __init__(self, references: ReferenceFolder, configuration: DependenciesConfi self.available_alleles = references.get_available_alleles() # NOTE: these resources do not read any file thus can be initialised fast - self.neoag_calculator = NeoagCalculator(runner=self.runner, configuration=configuration) self.mhc_database = references.get_mhc_database() self.mhc_parser = MhcParser.get_mhc_parser(self.mhc_database) diff --git a/neofox/published_features/neoag/__init__.py b/neofox/published_features/neoag/__init__.py deleted file mode 100755 index 4a64d329..00000000 --- a/neofox/published_features/neoag/__init__.py +++ /dev/null @@ -1,18 +0,0 @@ -# -# Copyright (c) 2020-2030 Translational Oncology at the Medical Center of the Johannes Gutenberg-University Mainz gGmbH. -# -# This file is part of Neofox -# (see https://github.com/tron-bioinformatics/neofox). -# -# This program is free software: you can redistribute it and/or modify -# it under the terms of the GNU General Public License as published by -# the Free Software Foundation, either version 3 of the License, or -# (at your option) any later version. -# -# This program is distributed in the hope that it will be useful, -# but WITHOUT ANY WARRANTY; without even the implied warranty of -# MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. 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at Chapel Hill (UNC). UNC grants to -RECIPIENT a royalty-free, nonexclusive, and nontransferable license to use the -Program for non-commercial research purposes only. Title and copyright to the -Program and any associated documentation shall at all times remain with UNC. -RECIPIENT acknowledges that the Program is a research tool still in the -development stage and that it is being supplied "as is," without any -accompanying services or improvements from UNC. RECIPIENT agrees to use the -Program solely for internal purposes and shall not distribute or transfer it -to another location or to any other person without prior written permission -from UNC. diff --git a/neofox/published_features/neoag/neoag-master/NeoAg_immunogenicity_predicition_GBM.R b/neofox/published_features/neoag/neoag-master/NeoAg_immunogenicity_predicition_GBM.R deleted file mode 100755 index 4a98c969..00000000 --- a/neofox/published_features/neoag/neoag-master/NeoAg_immunogenicity_predicition_GBM.R +++ /dev/null @@ -1,75 +0,0 @@ -############################################################# -##################TCGA NeoAg analysis######################## -############################################################# - -#Original analysis run in R v3.5.2 - -library(caret) #Original analysis run in v6.0-84 -library(Peptides) #Original analysis run in v2.4 -library(data.table) #Original analysis run in v1.12.0 -library(doParallel) #Original analysis run in v1.0.14 -registerDoParallel(1) #Can change to suitable number of threads - -args = commandArgs(trailingOnly=TRUE) - -path_to_file <- args[1] -neo_tab_path <- args[2] -outifle <- args[3] - - -#Input paths -# neo_tab_path = "./TCGA_neoAg_example.txt" -# GBM_model_path = "./NeoAg_immunogenicity/Final_gbm_model.rds" -#neo_tab_path = paste(path_to_file, "TCGA_neoAg_example.txt", sep = "") -GBM_model_path = paste(path_to_file, "Final_gbm_model.rds", sep = "/") -#neo_tab_path = "/projects/SUMMIT/WP1.2/input/development/neoag/tmp_neoag_kZe31d.txt" -#neo_tab_path = "/projects/SUMMIT/WP1.2/input/development/neoag/neoag-master/TCGA_neoAg_example.txt" - - -#Example input -neo_tab = fread(neo_tab_path) - -#Function for generating independent variables for the GBM model -model_process = function(n){ - c( - ifelse(substr(neo_tab$mut_peptide[n],1,1) == "V",1,0), - - ifelse(substr(neo_tab$mut_peptide[n],nchar(neo_tab$mut_peptide[n]),nchar(neo_tab$mut_peptide[n])) == "V",1,0), - - ifelse(aaComp(substr(neo_tab$mut_peptide[n],nchar(neo_tab$mut_peptide[n]),nchar(neo_tab$mut_peptide[n])))[[1]][2] == 1,1,0), - - ifelse(aaComp(substr(neo_tab$Reference[n],neo_tab$peptide_variant_position[n],neo_tab$peptide_variant_position[n]))[[1]][8] == 1,1,0), - - (aaComp(substr(neo_tab$mut_peptide[n],neo_tab$peptide_variant_position[n],neo_tab$peptide_variant_position[n]))[[1]][2] - - aaComp(substr(neo_tab$Reference[n],neo_tab$peptide_variant_position[n],neo_tab$peptide_variant_position[n]))[[1]][2]), - - ifelse("K" %in% unlist(strsplit(substr(neo_tab$mut_peptide[n],1,nchar(neo_tab$mut_peptide[n])-7),"|")),1,0), - - ifelse("V" %in% unlist(strsplit(substr(neo_tab$mut_peptide[n],1,3),"|")),1,0) - ) -} - -#Multi-thread derivation of features -model_mat = foreach(n = 1:nrow(neo_tab), .combine = rbind) %dopar% model_process(n) - -# only one epitope-df -if(is(model_mat, "numeric")){ - model_mat <- as.data.frame(t(model_mat)) -} - -colnames(model_mat) = c("Absolute_position_1_V", "Last_position_V", "Last_position_Small", "Reference_AA_at_mutated_position_Basic", - "Mutated_position_change_of_Small_feature", "Relative_site_1_K", "First_three_AA_V" ) -############################################################## - -#Formatting, binding input matrix with feature sset -neo_tab_final = cbind(neo_tab, model_mat) - -#Read in the GBM R object, run on the matrix generated above -Final_model = readRDS(GBM_model_path) - -#Predicting neoantigen immunogenicity scores from above GBM model -TCGA_predict = predict(Final_model, newdata = model_mat, type = "raw") - -TCGA_predict <- ifelse(length(TCGA_predict) == 0, NA, TCGA_predict ) - -cat(TCGA_predict) diff --git a/neofox/published_features/neoag/neoag_gbm_model.py b/neofox/published_features/neoag/neoag_gbm_model.py deleted file mode 100755 index 4f1633bc..00000000 --- a/neofox/published_features/neoag/neoag_gbm_model.py +++ /dev/null @@ -1,98 +0,0 @@ -#!/usr/bin/env python -# -# Copyright (c) 2020-2030 Translational Oncology at the Medical Center of the Johannes Gutenberg-University Mainz gGmbH. -# -# This file is part of Neofox -# (see https://github.com/tron-bioinformatics/neofox). -# -# This program is free software: you can redistribute it and/or modify -# it under the terms of the GNU General Public License as published by -# the Free Software Foundation, either version 3 of the License, or -# (at your option) any later version. -# -# This program is distributed in the hope that it will be useful, -# but WITHOUT ANY WARRANTY; without even the implied warranty of -# MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the -# GNU General Public License for more details. -# -# You should have received a copy of the GNU General Public License -# along with this program. If not, see .# - -import os -from neofox.helpers import intermediate_files -from neofox.helpers.epitope_helper import EpitopeHelper -from neofox.model.neoantigen import Annotation, PredictedEpitope, Neoantigen -from neofox.model.factories import AnnotationFactory - - -class NeoagCalculator(object): - - def __init__(self, runner, configuration): - """ - :type runner: neofox.helpers.runner.Runner - :type configuration: neofox.references.DependenciesConfiguration - """ - self.runner = runner - self.configuration = configuration - - def _apply_gbm(self, tmp_in): - """this function calls NeoAg tool. this tool applys a gradient boosting machine based on biochemical features - to epitopes (predicted seqs) - """ - my_path = os.path.abspath(os.path.dirname(__file__)) - model_path = os.path.join(my_path, "neoag-master") - tool_path = os.path.join( - my_path, "neoag-master/NeoAg_immunogenicity_predicition_GBM.R" - ) - cmd = [self.configuration.rscript, tool_path, model_path, tmp_in] - output, _ = self.runner.run_command(cmd) - return output - - def _prepare_tmp_for_neoag( - self, - sample_id, - mut_peptide, - score_mut, - ref_peptide, - peptide_variant_position, - tmp_file_name, - ): - """writes necessary epitope information into temporary file for neoag tool; only for epitopes with - affinity < 500 nM - """ - header = ["Sample_ID", "mut_peptide", "Reference", "peptide_variant_position"] - try: - epi_row = "\t".join( - [sample_id, mut_peptide, ref_peptide, str(peptide_variant_position)] - ) - except ValueError: - epi_row = "\t".join(["NA", "NA", "NA", "NA"]) - with open(tmp_file_name, "w") as f: - f.write("\t".join(header) + "\n") - f.write(epi_row + "\n") - - def calculate_neoag_score(self, epitope: PredictedEpitope): - tmp_file_name = intermediate_files.create_temp_file( - prefix="tmp_neoag_", suffix=".txt" - ) - self._prepare_tmp_for_neoag( - "*****", - epitope.mutated_peptide, - epitope.affinity_mutated, - epitope.wild_type_peptide, - EpitopeHelper.position_of_mutation_epitope(epitope=epitope), - tmp_file_name, - ) - neoag_score = self._apply_gbm(tmp_file_name) - os.remove(tmp_file_name) - return neoag_score - - def get_annotation(self, epitope_mhci: PredictedEpitope, neoantigen: Neoantigen) -> Annotation: - """wrapper function to determine neoag immunogenicity score for a mutated peptide sequence""" - - neoag_score = None - if neoantigen.wild_type_xmer and epitope_mhci.mutated_peptide and epitope_mhci.wild_type_peptide: - neoag_score = self.calculate_neoag_score(epitope=epitope_mhci) - - annotation = AnnotationFactory.build_annotation(value=neoag_score, name="Neoag_immunogenicity") - return annotation diff --git a/neofox/tests/integration_tests/test_neoag.py b/neofox/tests/integration_tests/test_neoag.py deleted file mode 100755 index 35caf85d..00000000 --- a/neofox/tests/integration_tests/test_neoag.py +++ /dev/null @@ -1,66 +0,0 @@ -# -# Copyright (c) 2020-2030 Translational Oncology at the Medical Center of the Johannes Gutenberg-University Mainz gGmbH. -# -# This file is part of Neofox -# (see https://github.com/tron-bioinformatics/neofox). -# -# This program is free software: you can redistribute it and/or modify -# it under the terms of the GNU General Public License as published by -# the Free Software Foundation, either version 3 of the License, or -# (at your option) any later version. -# -# This program is distributed in the hope that it will be useful, -# but WITHOUT ANY WARRANTY; without even the implied warranty of -# MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the -# GNU General Public License for more details. -# -# You should have received a copy of the GNU General Public License -# along with this program. If not, see .# -from unittest import TestCase - -from neofox.model.neoantigen import Annotation, PredictedEpitope, MhcAllele -from neofox.published_features.neoag.neoag_gbm_model import NeoagCalculator -from neofox.helpers.runner import Runner -import neofox.tests.integration_tests.integration_test_tools as integration_test_tools -from neofox.tests.tools import get_neoantigen - - -class TestNeoantigenFitness(TestCase): - def setUp(self): - self.references, self.configuration = integration_test_tools.load_references() - self.fastafile = integration_test_tools.create_temp_aminoacid_fasta_file() - self.runner = Runner() - - def test_neoag(self): - - mutation = get_neoantigen( - mutated_xmer= "DEVLGEPSQDILVTDQTRLEATISPET", - wild_type_xmer="DEVLGEPSQDILVIDQTRLEATISPET" - ) - result = NeoagCalculator( - runner=self.runner, configuration=self.configuration - ).get_annotation( - epitope_mhci=PredictedEpitope( - mutated_peptide="ILVTDQTRL", wild_type_peptide="ILVIDQTRL", - affinity_mutated=0, position=0, allele_mhc_i=MhcAllele(name="hla"), rank_mutated=0 - ), - neoantigen=mutation, - ) - self.assertTrue(isinstance(result, Annotation)) - self.assertTrue(float(result.value) > 0) - - def test_affinity_threshold(self): - mutation = get_neoantigen( - mutated_xmer="DEVLGEPSQDILVTDQTRLEATISPET", - wild_type_xmer="DEVLGEPSQDILVIDQTRLEATISPET", - ) - result = NeoagCalculator( - runner=self.runner, configuration=self.configuration - ).get_annotation( - epitope_mhci=PredictedEpitope( - mutated_peptide="DDDDDV", affinity_mutated=10, position=0, allele_mhc_i=MhcAllele(name="hla"), - rank_mutated=0 - ), - neoantigen=mutation - ) - self.assertEqual(result.value, "NA") diff --git a/neofox/tests/integration_tests/test_neofox.py b/neofox/tests/integration_tests/test_neofox.py index 531430e8..76a18bb9 100755 --- a/neofox/tests/integration_tests/test_neofox.py +++ b/neofox/tests/integration_tests/test_neofox.py @@ -204,7 +204,7 @@ def test_neofox_model_input(self): ).get_annotations() self.assertEqual(5, len(annotations)) self.assertIsInstance(annotations[0], Neoantigen) - self.assertEqual(len(annotations[0].neofox_annotations.annotations), 105) + self.assertEqual(len(annotations[0].neofox_annotations.annotations), 104) def test_neofox_without_mixmhcpreds(self): """ @@ -328,7 +328,7 @@ def test_neofox_without_mhc2(self): ).get_annotations() self.assertEqual(5, len(annotations)) self.assertIsInstance(annotations[0], Neoantigen) - self.assertEqual(len(annotations[0].neofox_annotations.annotations), 80) + self.assertEqual(len(annotations[0].neofox_annotations.annotations), 79) def test_neofox_without_mhc1(self): neoantigens, patients = self._get_test_data() From 9e9ce464b96879e9747b5f56ee77b381faf728ab Mon Sep 17 00:00:00 2001 From: nguyenhv Date: Thu, 19 Oct 2023 09:57:07 +0200 Subject: [PATCH 81/83] Update docu after removing NeoAg --- README.md | 1 - docs/source/01_overview.md | 1 - docs/source/03_02_output_data.md | 1 - neofox/annotator/neoantigen_annotator.py | 1 - 4 files changed, 4 deletions(-) diff --git a/README.md b/README.md index 488752d0..eb426c40 100755 --- a/README.md +++ b/README.md @@ -42,7 +42,6 @@ NeoFox covers the following neoantigen features and prediction algorithms: | Vaxrank | Rubinsteyn, 2017, Front Immunol | https://doi.org/10.3389/fimmu.2017.01807 | | Priority score | Bjerregaard et al, 2017, Cancer Immunol Immunother. | https://doi.org/10.1007/s00262-017-2001-3 | | Tcell predictor | Besser et al, 2019, Journal for ImmunoTherapy of Cancer | https://doi.org/10.1186/s40425-019-0595-z | -| neoag | Smith et al, 2019, Cancer Immunology Research | https://doi.org/10.1158/2326-6066.CIR-19-0155 | | PRIME § | Schmidt et al., 2021, Cell Reports Medicine | https://doi.org/10.1016/j.xcrm.2021.100194 | | HEX § | Chiaro et al., 2021, Cancer Immunology Research | https://doi.org/10.1158/2326-6066.CIR-20-0814 | diff --git a/docs/source/01_overview.md b/docs/source/01_overview.md index a8f57019..3188acc6 100644 --- a/docs/source/01_overview.md +++ b/docs/source/01_overview.md @@ -43,7 +43,6 @@ A list of implemented features and their references are given in Table 1. Please | Vaxrank | Rubinsteyn, 2017, Front Immunol | https://doi.org/10.3389/fimmu.2017.01807 | | Priority score | Bjerregaard et al., 2017, Cancer Immunol Immunother. | https://doi.org/10.1007/s00262-017-2001-3 | | Tcell predictor | Besser et al., 2019, Journal for ImmunoTherapy of Cancer | https://doi.org/10.1186/s40425-019-0595-z | -| neoag | Smith et al., 2019, Cancer Immunology Research | https://doi.org/10.1158/2326-6066.CIR-19-0155 | | PRIME v2.0 § | Schmidt et al., 2021, Cell Reports Medicine | https://doi.org/10.1016/j.xcrm.2021.100194 | | HEX § | Chiaro et al., 2021, Cancer Immunology Research | https://doi.org/10.1158/2326-6066.CIR-20-0814 | diff --git a/docs/source/03_02_output_data.md b/docs/source/03_02_output_data.md index b90e4e60..fce7159f 100755 --- a/docs/source/03_02_output_data.md +++ b/docs/source/03_02_output_data.md @@ -104,7 +104,6 @@ The following table describes each of the annotations in the output: | Priority_score_fromRNA | combinatorial score of several features such as MHC binding, transcription expression and VAF in RNA | Priority score | | Priority_score_imputed_fromDNA | combinatorial score of several features such as MHC binding, imputed gene expression and VAF in DNA | Priority score | | Priority_score_imputed_fromRNA | combinatorial score of several features such as MHC binding, imputed gene expression and VAF in RNA | Priority score | -| Neoag_immunogenicity | output score of neoag model | neoag | | IEDB_Immunogenicity_MHCI | IEDB Immunogenicity score for `NetMHCpan_bestAffinity_peptide` | IEDB Immunogenicity | | IEDB_Immunogenicity_MHCII | IEDB Immunogenicity score for `NetMHCIIpan_bestAffinity_peptide` | IEDB Immunogenicity | | MixMHCpred_bestScore_peptide | MHC class I neoepitope candidate sequence with maximum MixMHCpred score over all neoepitope canidates (8-11mers) and MHC I alleles | MixMHCpred | diff --git a/neofox/annotator/neoantigen_annotator.py b/neofox/annotator/neoantigen_annotator.py index d63fa6d5..fd2d6d86 100755 --- a/neofox/annotator/neoantigen_annotator.py +++ b/neofox/annotator/neoantigen_annotator.py @@ -56,7 +56,6 @@ def __init__(self, references: ReferenceFolder, configuration: DependenciesConfi self.rank_mhcii_threshold = rank_mhcii_threshold # NOTE: these resources do not read any file thus can be initialised fast - #self.neoag_calculator = NeoagCalculator(runner=self.runner, configuration=configuration) self.expression_calculator = Expression() self.mhc_database = references.get_mhc_database() self.mhc_parser = MhcParser.get_mhc_parser(self.mhc_database) From fe6de89682015f760dcaf8b72eb924e045f7af74 Mon Sep 17 00:00:00 2001 From: Franziska Lang Date: Thu, 26 Oct 2023 08:22:05 +0200 Subject: [PATCH 82/83] update documentation --- README.md | 6 +++--- docs/figures/figure1_v3b.png | Bin 0 -> 1604279 bytes docs/source/01_overview.md | 2 +- docs/source/02_installation.md | 7 +++++-- docs/source/03_02_output_data.md | 8 ++++---- 5 files changed, 13 insertions(+), 10 deletions(-) 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zMpzkeWAe@jJcc*0{poxfautb2)NB!whzy!);NGU9Ai73B+N`KhTu@BhE*62C9=5J- zF`7=qpI-+R7o7Yph$H)004gfu{|SnJHep~B0sr{x${x`4ATo=CBNt&XaOl;nYW@0r z2do5GicGu=D&PMk7@tp4vl~`7!gwpZj$mW6Oor`Vuo(4rZ$V1fQnXT5pZlu=wnaULoyie{Pzx$#&#~-1vLVYA&7Yf)`wZo2ybxPq{NbmvP7Fl z&y-IL{te|3K*bb10_&GXOVcnF-ZKfN5Kmf_sv3u%k3MBoz{%G>1-%@kr&*^7!TBh~ z$0NQqv_3hSkaGMlI6E?jsIzg}DN_%SXe9 zGz|(FVuOwppy}L~i_u>wV6%dWHdS0J)Q~wf<**z{UCTx+{Cz_(xpiMrlp#HeS+u8r zdJ#|0q6cfH(9J+t!G8<`EvToo)X&oB0dxV{yuBy6skfVXvpY3&D1^bGKScwFnh?B@ zF;*i9OKQZE% Date: Thu, 26 Oct 2023 15:18:18 +0200 Subject: [PATCH 83/83] increase vers --- neofox/__init__.py | 2 +- 1 file changed, 1 insertion(+), 1 deletion(-) diff --git a/neofox/__init__.py b/neofox/__init__.py index 687c4d4d..8d99b4a7 100755 --- a/neofox/__init__.py +++ b/neofox/__init__.py @@ -18,7 +18,7 @@ # along with this program. If not, see .# -VERSION = "1.1.0b30" +VERSION = "1.1.0" REFERENCE_FOLDER_ENV = "NEOFOX_REFERENCE_FOLDER" NEOFOX_BLASTP_ENV = "NEOFOX_BLASTP"

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