Genome Nexus VEP

Genome Nexus VEP is a small REST wrapper around the Ensembl Variant Effect Predictor (VEP) command line interface. It exposes the following endpoints to interface with VEP:

GET /vep/human/hgvs/{variant}
POST /vep/human/hgvs

Each endpoint expects variant(s) to be in HGVS format. See the implementation here.

Software Requirements

Make sure you fave the following installed

• Java version: 21
• Maven version: >= 3.6.3
• Docker

Download the Ensembl Data

Download the core database (Required)

1. Download the core database for the ensembl data version you wish to install. The URL containing the data files should be of the format https://ftp.ensembl.org/pub/release-112/mysql/homo_sapiens_core_XXX_<ASSEMBLY_VERSION>/.
2. Follow the installation instructions to set up your database.
3. Point the VEP at your database in your application properties.

Supporting Polyphen & Sift Predictions (Optional)

1. Download the SQLite database corresponding to the data version pointed to by your application properties. The URL containing the database should be of the format https://ftp.ensembl.org/pub/release-XXX/.
2. Download the PolyPhen_SIFT Perl Module corresponding to the data version pointed to by your application properties. The URL containing the file should be of the format https://github.com/Ensembl/VEP_plugins/blob/release/XXX/PolyPhen_SIFT.pm.
3. Place both your installed database and the PolyPhen_SIFT Perl Module in the plugin-data directory.
4. Set the polyphen-sift-filename property in your application properties to the name of the installed database file.

Supporting AlphaMissense Pathogenicity Scores (Optional)

1. Download the prediction score file corresponding to your assembly version (AlphaMissense_hg19.tsv.gz for GRCh37 or AlphaMissense_hg38.tsv.gz for GRCh38).
2. Place the file in the plugin-data directory.
3. Run tabix -s 1 -b 2 -e 2 -f <PREDICTION_SCORE_FILE>.
4. Set the alpha-missense-filename property in your application properties to the name of the installed file (not the generated tabix file).

Development

1. Run ./scripts/init_vep.sh <ensemblorg/ensembl-vep:tag> to install and run a VEP docker image, specifying the tag you wish to use. This will also generate a script to be used by the application, ./scripts/vep, which should not be modified.
2. Set your VEP configuration in application-dev.yaml.
3. Run mvn spring-boot:run -Dspring-boot.run.profiles=dev

Building for Production

1. Make sure the VEP version is correct in the Dockerfile.
2. Set your VEP configuration in application-prod.yaml.
   IMPORTANT: Make sure vep.version is the same as the version used in the Dockerfile. This version will be attached to all responses from the server.
3. Run docker build <DOCKER_ARGS> . to build the production image.