Genomics WGS Risk Analysis Pipeline

Structured, reproducible local pipeline for personal WGS analysis with two stages:

• Monogenic triage from ClinVar-enriched VEP output.
• Polygenic risk scoring (PRS) via pgscatalog/pgsc_calc.

This repository is publish-safe by default:

• Real secrets and local machine paths are ignored by git.
• Example config files with fake values are tracked.

Project Layout

• workflow/run_pipeline.sh: single entrypoint orchestrating stages.
• workflow/monogenic/: monogenic analysis scripts.
• workflow/prs/: PRS prep and execution scripts.
• workflow/utils/: utility helpers.
• config/*.example*: tracked templates.
• docs/: architecture and runbooks.
• results/, logs/, work/, .nextflow/: generated artifacts (ignored).

Quick Start

1. Bootstrap local config files:

make bootstrap

2. Edit local files (ignored by git):

• config/pipeline.env
• config/secrets.env
• .env
• config/prs_samplesheet.csv (or set auto-build)
• config/prs_pgs_ids.txt

3. Run validation checks:

make validate
make prepublish

4. Run pipeline:

# full pipeline
make pipeline

# monogenic only
make monogenic

# PRS only
make prs

Pipeline Configuration

Primary runtime config: config/pipeline.env

Key variables:

• SAMPLE_ID: logical sample identifier for outputs.
• ANNOTATED_VCF_GZ: path to ClinVar-enriched VEP VCF (.vcf.gz).
• RUN_MONOGENIC / RUN_PRS: enable stages in --stage all mode.
• MONOGENIC_MODE, MONOGENIC_MAX_AF: triage strictness.
• PRS_AUTOBUILD_SAMPLESHEET: set 1 to build from config/paths.env.
• PRS_SAMPLESHEET, PRS_PGS_IDS_FILE: PRS inputs.
• PGSC_PROFILE, PGSC_MAX_MEMORY, PGSC_MIN_OVERLAP, PGSC_RESUME: pgsc_calc runtime controls.

Optional secret files:

• .env (from .env.example)
• config/secrets.env (from config/secrets.env.example)

Both are auto-loaded if present.

Security and Publishing

Ignored by default:

• Real env/secrets files (.env, config/secrets.env, config/pipeline.env, etc.)
• Local path configs (config/paths.env, config/prs_*.csv|txt|tsv local variants)
• Runtime/cache/output artifacts

Before publishing:

1. Confirm git status does not include private/local files.
2. Keep only *.example* templates for configuration.
3. Do not commit generated results/ or logs/.

CI

GitHub Actions workflow at .github/workflows/ci.yml runs:

• Python syntax checks
• Shell lint and syntax checks
• Pipeline help/entrypoint check

Disclaimer

This project is for research/hobby analysis and is not a medical diagnostic system.

License

MIT. See LICENSE.