cpg-flow exomiser

An extraction and reimplementation of the Exomiser workflow implemented at The Centre for Population Genomics.

Original source in Production-Pipelines Here

This repository contains a workflow built using the CPG-Flow framework, which is a Hail Batch based workflow executor.

Purpose

This workflow generates Exomiser results for families.

It does this by identifying families which have not previously received an analysis, creating a pseudo-joint-call from all members of the family, pulling all the family members' metadata into a phenopacket, and running Exomiser.

Multiple single-family analyses are stacked into a single VM and executed in parallel, to make best use of the localised annotation resources (large files).

Once analysis is complete, the resulting Gene- and Variant-level result TSVs are aggregated.

• The Gene-level results are placed into a Seqr-ready format to be used in enhanced gene searches
• The Variant-level results are placed into a Talos-ready format to be used in variant prioritisation

This workflow is built into a single-pipeline docker container, but Exomiser itself is available as a secondary container, with a build file defined in the CPG images repository here. The code from this workflow, and workflow setup itself is handled in the container derived from this workflow's Dockerfile. The Exomiser process is handled by the dedicated Exomiser container.

Structure

src
├── cpg_exomiser
│   ├── __init__.py
│   ├── config_template.toml
│   ├── jobs
│   │   ├── CreateFamilyVcfs.py
│   │   ├── MakePedExtracts.py
│   │   ├── MakePhenopackets.py
│   │   └── RunExomiser.py
│   ├── run_workflow.py
│   ├── scripts
│   │   ├── combine_exomiser_gene_tsvs.py
│   │   └── combine_exomiser_variant_tsvs.py
│   ├── stages.py
│   ├── utils.py

• cpg_exomiser/config_template.toml - A template config file for the workflow, showing all the fields specific to this workflow. This is derived from the production-pipelines default config for this workflow
• cpg_exomiser/run_workflow.py is the main entrypoint for the workflow, and is aliased to the command run_workflow when this pipeline is installed as a package
• cpg_exomiser/jobs contains a separate file per Stage in the workflow, containing all the logic to carry out a given Stage's operations
• cpg_exomiser/scripts contains a separate file per standalone script used in the workflow, containing all the logic to carry out a given script's operations. These scripts are aliased within pyproject.toml to be available as commands in the container