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[package.dependencies] @@ -2480,4 +2499,4 @@ type = ["pytest-mypy"] [metadata] lock-version = "2.0" python-versions = "^3.11" -content-hash = "e39023febff49a0294816d627b40b30b8838e33be0e55651998d749ba2ec6e06" +content-hash = "1bb5c5158bcc6044747d5fa751ebe05a160d00215d869aa60322ef984cffb2bc" diff --git a/prymer/api/oligo.py b/prymer/api/oligo.py index b8ea01c..6de5902 100644 --- a/prymer/api/oligo.py +++ b/prymer/api/oligo.py @@ -208,7 +208,7 @@ def __str__(self) -> str: """ # If the bases field is None, replace with MISSING_BASES_STRING bases: str = self.bases if self.bases is not None else MISSING_BASES_STRING - return f"{bases}\t{self.tm}\t{self.penalty}\t{self.span}" + return f"{bases}\t{self.tm:.2f}\t{self.penalty:.2f}\t{self.span}" @classmethod def _parsers(cls) -> Dict[type, Callable[[str], Any]]: diff --git a/prymer/api/picking.py b/prymer/api/picking.py index ce65059..020571e 100644 --- a/prymer/api/picking.py +++ b/prymer/api/picking.py @@ -165,13 +165,13 @@ def build_primer_pairs( # noqa: C901 # If the right primer isn't "to the right" of the left primer, move on if rp.span.start < lp.span.start or lp.span.end > rp.span.end: - first_right_primer_idx = max(first_right_primer_idx, j+1) + first_right_primer_idx = max(first_right_primer_idx, j + 1) continue amp_span = PrimerPair.calculate_amplicon_span(lp, rp) if amp_span.length < amplicon_sizes.min: - first_right_primer_idx = max(first_right_primer_idx, j+1) + first_right_primer_idx = max(first_right_primer_idx, j + 1) continue if amp_span.length > amplicon_sizes.max: diff --git a/prymer/primer3/primer3.py b/prymer/primer3/primer3.py index 7dd2b92..544a80c 100644 --- a/prymer/primer3/primer3.py +++ b/prymer/primer3/primer3.py @@ -4,13 +4,6 @@ This module contains the [`Primer3`][prymer.primer3.primer3.Primer3] class, a class to facilitate exchange of input and output data with Primer3, a command line tool. -Similar to the [`NtThermoAlign`][prymer.ntthal.NtThermoAlign] and -[`BwaAlnInteractive`][prymer.offtarget.bwa.BwaAlnInteractive] classes in the `prymer` -library, the Primer3 class extends the -[`ExecutableRunner`][prymer.util.executable_runner.ExecutableRunner] base class to -initiate an underlying subprocess, read and write input and output data, and gracefully terminate -any remaining subprocesses. - ## Examples The genome FASTA must be provided to the `Primer3` constructor, such that design and target @@ -93,19 +86,18 @@ ```python >>> for primer in left_result.primers(): \ print(primer) -TCTGAACAGGACGAACTGGATTTCCTCAT 65.686 1.953897 chr1:163-191:+ -CTCTGAACAGGACGAACTGGATTTCCTCAT 66.152 2.293213 chr1:162-191:+ -TCTGAACAGGACGAACTGGATTTCCTCATG 66.33 2.514048 chr1:163-192:+ -AACAGGACGAACTGGATTTCCTCATGGAA 66.099 2.524986 chr1:167-195:+ -CTGAACAGGACGAACTGGATTTCCTCATG 65.47 2.556859 chr1:164-192:+ +TCTGAACAGGACGAACTGGATTTCCTCAT 65.69 1.95 chr1:163-191:+ +CTCTGAACAGGACGAACTGGATTTCCTCAT 66.15 2.29 chr1:162-191:+ +TCTGAACAGGACGAACTGGATTTCCTCATG 66.33 2.51 chr1:163-192:+ +AACAGGACGAACTGGATTTCCTCATGGAA 66.10 2.52 chr1:167-195:+ +CTGAACAGGACGAACTGGATTTCCTCATG 65.47 2.56 chr1:164-192:+ ``` -Finally, the designer should be closed to terminate the sub-process: +Finally, the designer should be closed to close access to the FASTA: ```python >>> designer.close() -True ``` @@ -119,19 +111,22 @@ """ # noqa: E501 -import logging -import subprocess import typing from collections import Counter +from contextlib import AbstractContextManager from dataclasses import dataclass from dataclasses import replace from pathlib import Path +from types import TracebackType +from typing import Any from typing import Generic from typing import Optional +from typing import Self from typing import TypeVar from typing import Union from typing import assert_never +import primer3 import pysam from fgpyo import sam from fgpyo.fasta.sequence_dictionary import SequenceDictionary @@ -153,7 +148,6 @@ from prymer.primer3.primer3_task import DesignPrimerPairsTask from prymer.primer3.primer3_task import DesignRightPrimersTask from prymer.primer3.primer3_task import PickHybProbeOnly -from prymer.util.executable_runner import ExecutableRunner @dataclass(init=True, slots=True, frozen=True) @@ -216,7 +210,7 @@ def primer_pairs(self) -> list[PrimerPair]: raise ValueError("Cannot call `primer_pairs` on `Oligo` results") from ex -class Primer3(ExecutableRunner): +class Primer3(AbstractContextManager): """ Enables interaction with command line tool, primer3. @@ -228,24 +222,17 @@ class Primer3(ExecutableRunner): def __init__( self, genome_fasta: Path, - executable: Optional[str] = None, variant_lookup: Optional[VariantLookup] = None, ) -> None: """ Args: genome_fasta: Path to reference genome .fasta file - executable: string representation of the path to primer3_core variant_lookup: VariantLookup object to facilitate hard-masking variants Assumes the sequence dictionary is located adjacent to the .fasta file and has the same base name with a .dict suffix. """ - executable_path = ExecutableRunner.validate_executable_path( - executable="primer3_core" if executable is None else executable - ) - command: list[str] = [f"{executable_path}"] - self.variant_lookup = variant_lookup self._fasta = pysam.FastaFile(filename=f"{genome_fasta}") @@ -255,21 +242,22 @@ def __init__( with reader(dict_path, file_type=sam.SamFileType.SAM) as fh: self._dict: SequenceDictionary = SequenceDictionary.from_sam(header=fh.header) - super().__init__(command=command, stderr=subprocess.STDOUT) + def __enter__(self) -> Self: + return self - def close(self) -> bool: - """Closes fasta file regardless of underlying subprocess status. - Logs an error if the underlying subprocess is not successfully closed. + def __exit__( + self, + exc_type: Optional[type[BaseException]], + exc_value: Optional[BaseException], + traceback: Optional[TracebackType], + ) -> None: + """Gracefully terminates any running subprocesses.""" + super().__exit__(exc_type, exc_value, traceback) + self.close() - Returns: - True: if the subprocess was terminated successfully - False: if the subprocess failed to terminate or was not already running - """ + def close(self) -> None: + """Closes fasta file.""" self._fasta.close() - subprocess_close = super().close() - if not subprocess_close: - logging.getLogger(__name__).debug("Did not successfully close underlying subprocess") - return subprocess_close def get_design_sequences(self, region: Span) -> tuple[str, str]: """Extracts the reference sequence that corresponds to the design region. @@ -354,17 +342,10 @@ def design(self, design_input: Primer3Input) -> Primer3Result: # noqa: C901 Primer3Result containing both the valid and failed designs emitted by Primer3 Raises: - RuntimeError: if underlying subprocess is not alive ValueError: if Primer3 returns errors or does not return output ValueError: if Primer3 output is malformed ValueError: if an unknown design task is given """ - - if not self.is_alive: - raise RuntimeError( - f"Error, trying to use a subprocess that has already been " - f"terminated, return code {self._subprocess.returncode}" - ) design_region: Span match design_input.task: case PickHybProbeOnly(): @@ -399,55 +380,33 @@ def design(self, design_input: Primer3Input) -> Primer3Result: # noqa: C901 **global_primer3_params, **design_input.to_input_tags(design_region=design_region), } - # Submit inputs to primer3 + + # split the tags into sequence and non-sequence tags + seq_args = {} + global_args = {} for tag, value in assembled_primer3_tags.items(): - self._subprocess.stdin.write(f"{tag}={value}") - self._subprocess.stdin.write("\n") - self._subprocess.stdin.write("=\n") - self._subprocess.stdin.flush() - - error_lines: list[str] = [] # list of errors as reported by primer3 - primer3_results: dict[str, str] = {} # key-value pairs of results reported by Primer3 - - def primer3_error(message: str) -> None: - """Formats the Primer3 error and raises a ValueError.""" - error_message = f"{message}: " - # add in any reported PRIMER_ERROR - if "PRIMER_ERROR" in primer3_results: - error_message += primer3_results["PRIMER_ERROR"] - # add in any error lines - if len(error_lines) > 0: - error_message += "\n".join(f"\t\t{e}" for e in error_lines) - # raise the exception now - raise ValueError(error_message) - - while True: - # Get the next line. Since we want to distinguish between empty lines, which we ignore, - # and the end-of-file, which is just an empty string, check for an empty string before - # stripping the line of any trailing newline or carriage return characters. - line: str = self._subprocess.stdout.readline() - if line == "": # EOF - primer3_error("Primer3 exited prematurely") - line = line.rstrip("\r\n") - - if line == "=": # stop when we find the line just "=" - break - elif line == "": # ignore empty lines - continue - elif "=" not in line: # error lines do not have the equals character in them, usually - error_lines.append(line) - else: # parse and store the result - key, value = line.split("=", maxsplit=1) - # Because Primer3 will emit both the input given and the output generated, we - # discard the input that is echo'ed back by looking for tags (keys) - # that do not match any Primer3InputTag - if not any(key == item.value for item in Primer3InputTag): - primer3_results[key] = value + if tag.is_sequence_arg: + seq_args[tag] = value + else: + global_args[tag] = value + design_primers_retval = primer3.design_primers(seq_args=seq_args, global_args=global_args) + primer3_results: dict[str, Any] = {} # key-value pairs of results reported by Primer3 + + for key, value in design_primers_retval.items(): + # Because Primer3 will emit both the input given and the output generated, we + # discard the input that is echo'ed back by looking for tags (keys) + # that do not match any Primer3InputTag + # NB:`key not in Primer3InputTag` is supported in python 3.12+, but not in 3.11, + # so we handle a KeyError + try: + Primer3InputTag[key] # checks if key is in the input tags + except KeyError: # the key is **not** in the input tags, so add it to the results + primer3_results[key] = value # Check for any errors. Typically, these are in error_lines, but also the results can # contain the PRIMER_ERROR key. - if "PRIMER_ERROR" in primer3_results or len(error_lines) > 0: - primer3_error("Primer3 failed") + if "PRIMER_ERROR" in primer3_results: + raise ValueError("Primer3 failed: " + primer3_results["PRIMER_ERROR"]) match design_input.task: case DesignPrimerPairsTask(): # Primer pair design @@ -484,7 +443,7 @@ def primer3_error(message: str) -> None: @staticmethod def _build_oligos( design_input: Primer3Input, - design_results: dict[str, str], + design_results: dict[str, Any], design_region: Span, design_task: Union[DesignLeftPrimersTask, DesignRightPrimersTask, PickHybProbeOnly], unmasked_design_seq: str, @@ -510,7 +469,7 @@ def _build_oligos( primers: list[Oligo] = [] for idx in range(count): key = f"PRIMER_{design_task.task_type}_{idx}" - str_position, str_length = design_results[key].split(",", maxsplit=1) + str_position, str_length = design_results[key] position, length = int(str_position), int(str_length) # position is 1-based match design_task: @@ -589,7 +548,7 @@ def _assemble_single_designs( @staticmethod def _build_primer_pairs( design_input: Primer3Input, - design_results: dict[str, str], + design_results: dict[str, Any], design_region: Span, unmasked_design_seq: str, ) -> list[PrimerPair]: @@ -652,7 +611,7 @@ def _build_primer_pair(num: int, primer_pair: tuple[Oligo, Oligo]) -> PrimerPair @staticmethod def _assemble_primer_pairs( design_input: Primer3Input, - design_results: dict[str, str], + design_results: dict[str, Any], unfiltered_designs: list[PrimerPair], ) -> Primer3Result: """Helper function to organize primer pairs into valid and failed designs. diff --git a/prymer/primer3/primer3_input_tag.py b/prymer/primer3/primer3_input_tag.py index 109614c..ac3c6b6 100644 --- a/prymer/primer3/primer3_input_tag.py +++ b/prymer/primer3/primer3_input_tag.py @@ -29,6 +29,18 @@ class Primer3InputTag(UppercaseStrEnum): Errors in these "global" input tags are fatal. """ + # Developer note: sequence-specific tags must be specified prior to global tags + + @property + def is_sequence_arg(self) -> bool: + """True if this is a sequence input tag (query-specific)""" + return self.name.startswith("SEQUENCE") + + @property + def is_global_arg(self) -> bool: + """True if this is a global input tags (will persist across primer3 queries)""" + return not self.is_sequence_arg + # Sequence input tags; query-specific SEQUENCE_EXCLUDED_REGION = auto() SEQUENCE_INCLUDED_REGION = auto() diff --git a/pyproject.toml b/pyproject.toml index 7e7bec1..86d10a0 100644 --- a/pyproject.toml +++ b/pyproject.toml @@ -40,6 +40,7 @@ strenum = "^0.4.15" fgpyo = "^0.8.0" pysam = "^0.22.1" ordered-set = "^4.1.0" +primer3-py = "^2.0.3" [tool.poetry.group.dev.dependencies] poetry = "^1.8.2" @@ -118,7 +119,7 @@ warn_unused_ignores = true exclude = ["site/", "docs/"] [[tool.mypy.overrides]] -module = "defopt" +module = ["defopt", "primer3"] ignore_missing_imports = true [tool.pytest.ini_options] diff --git a/tests/api/test_oligo.py b/tests/api/test_oligo.py index 09e9984..ec24337 100644 --- a/tests/api/test_oligo.py +++ b/tests/api/test_oligo.py @@ -94,7 +94,7 @@ def build_primer_test_cases() -> list[OligoTestCase]: gc_pct=0.0, longest_hp=1, longest_dinuc=4, - str_fields=["ATAT", "1.0", "2.0", "chr1:1-4:+"], + str_fields=["ATAT", "1.00", "2.00", "chr1:1-4:+"], ), OligoTestCase( primer=Oligo( @@ -106,7 +106,7 @@ def build_primer_test_cases() -> list[OligoTestCase]: gc_pct=16.667, longest_hp=6, longest_dinuc=6, - str_fields=["ACGTAAAAAATT", "1.0", "2.0", "chr1:1-12:+"], + str_fields=["ACGTAAAAAATT", "1.00", "2.00", "chr1:1-12:+"], ), OligoTestCase( primer=Oligo( @@ -118,7 +118,7 @@ def build_primer_test_cases() -> list[OligoTestCase]: gc_pct=25.0, longest_hp=1, longest_dinuc=2, - str_fields=["ATAC", "1.0", "2.0", "chr1:1-4:+"], + str_fields=["ATAC", "1.00", "2.00", "chr1:1-4:+"], ), OligoTestCase( primer=Oligo( @@ -130,7 +130,7 @@ def build_primer_test_cases() -> list[OligoTestCase]: gc_pct=33.333, longest_hp=2, longest_dinuc=4, - str_fields=["ATATCC", "1.0", "2.0", "chr1:1-6:+"], + str_fields=["ATATCC", "1.00", "2.00", "chr1:1-6:+"], ), OligoTestCase( primer=Oligo( @@ -142,7 +142,7 @@ def build_primer_test_cases() -> list[OligoTestCase]: gc_pct=50.0, longest_hp=1, longest_dinuc=2, - str_fields=["AGCT", "1.0", "2.0", "chr1:1-4:+"], + str_fields=["AGCT", "1.00", "2.00", "chr1:1-4:+"], ), OligoTestCase( primer=Oligo( @@ -154,7 +154,7 @@ def build_primer_test_cases() -> list[OligoTestCase]: gc_pct=100.0, longest_hp=5, longest_dinuc=4, - str_fields=["GGGGG", "1.0", "2.0", "chr1:1-5:+"], + str_fields=["GGGGG", "1.00", "2.00", "chr1:1-5:+"], ), OligoTestCase( primer=Oligo( @@ -166,7 +166,7 @@ def build_primer_test_cases() -> list[OligoTestCase]: gc_pct=62.5, longest_hp=2, longest_dinuc=2, - str_fields=["ccgTATGC", "1.0", "2.0", "chr1:1-8:+"], + str_fields=["ccgTATGC", "1.00", "2.00", "chr1:1-8:+"], ), OligoTestCase( primer=Oligo( @@ -178,7 +178,7 @@ def build_primer_test_cases() -> list[OligoTestCase]: gc_pct=50.0, longest_hp=1, longest_dinuc=0, - str_fields=["ACGT", "1.0", "2.0", "chr1:1-4:+"], + str_fields=["ACGT", "1.00", "2.00", "chr1:1-4:+"], ), OligoTestCase( primer=Oligo( @@ -190,7 +190,7 @@ def build_primer_test_cases() -> list[OligoTestCase]: gc_pct=46.154, longest_hp=1, longest_dinuc=8, - str_fields=["ACACACTCTCTCT", "1.0", "2.0", "chr1:1-13:+"], + str_fields=["ACACACTCTCTCT", "1.00", "2.00", "chr1:1-13:+"], ), ] diff --git a/tests/primer3/test_primer3.py b/tests/primer3/test_primer3.py index c74cb13..1c7e2ea 100644 --- a/tests/primer3/test_primer3.py +++ b/tests/primer3/test_primer3.py @@ -159,7 +159,7 @@ def test_design_raises( primer_and_amplicon_params=illegal_primer3_params, task=DesignLeftPrimersTask(), ) - with pytest.raises(ValueError, match="Primer3 failed"): + with pytest.raises(ValueError, match="Illegal PRIMER_NUM_RETURN value: invalid"): Primer3(genome_fasta=genome_ref).design(design_input=invalid_design_input) # TODO: add other Value Errors @@ -213,7 +213,6 @@ def test_left_primer_valid_designs( end=actual_design.span.end, ) assert actual_design.bases == underlying_ref_seq - assert designer.is_alive def test_right_primer_valid_designs( @@ -262,7 +261,6 @@ def test_right_primer_valid_designs( end=actual_design.span.end, ) assert actual_design.bases == reverse_complement(underlying_ref_seq) - assert designer.is_alive def test_primer_pair_design( @@ -356,7 +354,6 @@ def test_fasta_close_valid( assert designer._fasta.is_open() designer.close() assert designer._fasta.closed - assert not designer.is_alive target = Span(refname="chr1", start=201, end=250, strand=Strand.POSITIVE) design_input = Primer3Input( target=target, @@ -364,9 +361,7 @@ def test_fasta_close_valid( task=DesignLeftPrimersTask(), ) - with pytest.raises( - RuntimeError, match="Error, trying to use a subprocess that has already been terminated" - ): + with pytest.raises(ValueError, match="I/O operation on closed file"): designer.design(design_input=design_input) diff --git a/tests/primer3/test_primer3_input_tag.py b/tests/primer3/test_primer3_input_tag.py new file mode 100644 index 0000000..4d90c68 --- /dev/null +++ b/tests/primer3/test_primer3_input_tag.py @@ -0,0 +1,11 @@ +from prymer.primer3 import Primer3InputTag + + +def test_primer3_input_tag() -> None: + for tag in Primer3InputTag: + assert tag.is_sequence_arg == tag.startswith("S") + assert tag.is_global_arg == tag.startswith("P") + assert tag.is_global_arg != tag.is_sequence_arg + assert isinstance(Primer3InputTag[tag], Primer3InputTag) + # This is supported in python 3.12+, but not in 3.11 + # assert f"{tag}" in Primer3InputTag