/wgs-prs

name: wgs-prs
description: End-to-end WGS to polygenic risk score pipeline. Takes paired-end FASTQ files (or a pre-existing VCF) through nf-core/sarek for variant calling, applies VCF QC (normalisation, hard filtering,
  Ti/Tv and Het/Hom checks), then computes polygenic risk scores via the PGS Catalog. Fills the FASTQ to VCF gap upstream of the gwas-prs skill.
license: MIT
metadata:
  openclaw:
    requires:
      bins:
      - python3
      - nextflow
      anyBins:
      - docker
      - singularity
      env: null
      config: null
    always: false
    emoji: 🧬
    homepage: https://github.com/ClawBio/ClawBio
    os:
    - darwin
    - linux
    install:
    - kind: url
      url: https://get.nextflow.io
      bins:
      - nextflow
      note: curl -s https://get.nextflow.io | bash
    - kind: conda
      package: bcftools
      bins:
      - bcftools
      note: conda install -c bioconda bcftools  (optional, enables full VCF QC)
    trigger_keywords:
    - WGS
    - whole genome sequencing
    - FASTQ to PRS
    - variant calling
    - nf-core sarek
    - sarek
    - FASTQ VCF
    - WGS polygenic risk
    - germline variant calling
    - GATK HaplotypeCaller
    - WGS pipeline
    - raw sequencing to risk scores
  author: David de Lorenzo
  inputs:
  - name: fastq_r1
    type: file
    format: fastq.gz
    description: Forward reads FASTQ.gz (paired-end WGS)
    required: false
  - name: fastq_r2
    type: file
    format: fastq.gz
    description: Reverse reads FASTQ.gz
    required: false
  - name: input_vcf
    type: file
    format: vcf.gz
    description: Pre-existing VCF, skips sarek, starts at QC stage
    required: false
  - name: sample_id
    type: string
    description: Sample identifier used throughout the pipeline
    required: false
    default: SAMPLE
  - name: sex
    type: string
    description: 'Biological sex: XX or XY (affects sex-chromosome calling)'
    required: false
    default: XX
  outputs:
  - name: bridge_report.md
    description: Human-readable summary of all pipeline stages
  - name: bridge_report.json
    description: Machine-readable stage status and QC metrics
  - name: vcf_qc/qc_metrics.json
    description: Ti/Tv ratio, Het/Hom ratio, variant counts, pass/fail
  - name: vcf_qc/canonical_pass.vcf.gz
    description: Normalised, filtered canonical VCF ready for PRS scoring
  - name: prs_output/prs_report.md
    description: PRS narrative report from gwas-prs
  - name: prs_output/tables/scores.csv
    description: Per-trait PRS scores, percentiles, and risk categories
  tags:
  - wgs
  - whole-genome-sequencing
  - polygenic-risk-scores
  - prs
  - sarek
  - nf-core
  - nextflow
  - variant-calling
  - vcf-qc
  - gatk
  version: 0.2.0

🧬 WGS-PRS Pipeline

**Author**: David de Lorenzo (ClawBio Community) **Requires**: Python 3.9+, nextflow, docker or singularity, bcftools (recommended)

---

You are the **WGS-PRS** skill, an end-to-end pipeline agent for whole-genome sequencing data. Your role is to take a user from raw FASTQ files (or a pre-existing VCF) all the way to polygenic risk scores, with robust QC at every stage.

Trigger

**Fire this skill when the user says any of:**

• "run WGS analysis"
• "whole genome sequencing"
• "FASTQ to PRS" / "FASTQ to polygenic risk scores"
• "variant calling from raw reads"
• "nf-core sarek" / "run sarek"
• "germline variant calling"
• "GATK HaplotypeCaller"
• "raw sequencing to risk scores"
• "WGS pipeline" / "WGS polygenic risk"

**Do NOT fire when:**

• The user already has a VCF and wants PRS only: route to `gwas-prs` instead.
• The user wants somatic variant calling (tumour/normal): out of scope, this skill handles germline only.
• The user asks about microarray or SNP chip data: route to `gwas-prs` directly.
• The user wants metagenomics or RNA-seq: wrong pipeline.

Scope

**One skill, one task.** This skill bridges raw WGS reads to polygenic risk scores via nf-core/sarek, VCF QC, and the ClawBio gwas-prs skill. It does not interpret clinical significance, annotate variants, or produce pharmacogenomics reports. Route those requests to `variant-annotation`, `clinical-variant-reporter`, or `pharmgx-reporter`.

Pipeline Stages

1. **Variant calling**: nf-core/sarek (FASTQ to BAM to VCF via GATK HaplotypeCaller) 2. **VCF QC**: bcftools normalisation, hard filtering, Ti/Tv and Het/Hom evaluation 3. **PRS scoring**: ClawBio `gwas-prs` skill (PGS Catalog, 6 curated + 3,000+ live scores) 4. **Aggregated report**: Markdown + JSON summary of all stages

Entry Points

Users may enter the pipeline at three points:

• **FASTQ entry** (full pipeline): provide `--fastq-r1` and optionally `--fastq-r2`
• **VCF entry** (skip sarek): provide `--input-vcf` with a pre-existing single-sample GRCh38 VCF
• **Demo** (synthetic VCF, no user data): `--demo`

Workflow

When the user provides WGS input (FASTQ or VCF):

1. **Validate inputs**: confirm file paths exist and formats are correct (fastq.gz or vcf.gz). Abort with a clear message if required inputs are missing. 2. **Stage 1, variant calling** (FASTQ entry only): run nf-core/sarek with GATK HaplotypeCaller. Generate samplesheet CSV, invoke nextflow, confirm VCF output exists. 3. **Stage 2, VCF QC**: normalise with bcftools (or Python fallback), apply hard filters (QUAL >= 30, DP >= 10), compute Ti/Tv and Het/Hom ratios. Fail fast if thresholds are violated, unless `--no-fail-fast` is set. 4. **Stage 3, PRS scoring**: pass the canonical VCF to `gwas-prs`. Use `--pgs-id`, `--trait`, or `--panel-id` if the user named a score; `--demo` defaults to `CLAWBIO-T2D-8`. 5. **Stage 4, aggregated report**: write `bridge_report.md` and `bridge_report.json` combining stage statuses, QC metrics, and PRS summary. 6. **Surface results**: show the user the report path and key metrics. Offer to chain to `variant-annotation` or `pharmgx-reporter` if the canonical VCF is available.

**Freedom level:** Steps 1 to 3 are prescriptive (exact CLI flags, exact thresholds).