/nfcore-sarek-wrapper

name: nfcore-sarek-wrapper
description: ClawBio wrapper around nf-core/sarek 3.8.1 covering mapping through annotation for germline, tumor-only, and somatic paired analyses.
license: MIT
metadata:
  version: "0.1.0"
  author: ClawBio
  domain: genomics
  tags:
    - sarek
    - variant-calling
    - germline
    - somatic
    - tumor-only
    - wes
    - wgs
    - nextflow
    - nf-core
  inputs:
    - name: samplesheet
      type: file
      format:
        - csv
        - tsv
        - yaml
        - yml
        - json
      description: >
        nf-core/sarek samplesheet. Accepted formats: .csv, .tsv, .yaml, .yml,
        .json. Always-required columns: patient, sample. Step-dependent columns:
        for mapping, lane plus one input mode — fastq_1 + fastq_2,
        OR spring_1 (+ optional spring_2), OR bam (uBAM); for markduplicates/
        prepare_recalibration/variant_calling, bam+bai or cram+crai; for
        recalibrate, additionally table; for annotate, vcf (+ optional
        variantcaller). Optional metadata columns: sex (XX/XY/NA), status
        (0=normal, 1=tumor), contamination (varlociraptor). A row may not mix
        FASTQ, BAM/CRAM, and VCF input modes.
      required: true
  outputs:
    - name: report
      type: file
      format:
        - md
      description: Wrapper run summary, per-tool VCF inventory, and downstream handoff recommendations
    - name: result
      type: file
      format:
        - json
      description: Structured result payload with detected CRAMs, per-tool VCFs, MultiQC HTML, and provenance
  dependencies:
    python: ">=3.11"
    packages:
  demo_data:
    - path: demo/README.md
      description: Demo mode uses the upstream nf-core/sarek -profile test dataset rather than bundled FASTQs
  endpoints:
    cli: python clawbio.py run sarek-pipeline --input {samplesheet} --output {output_dir}
  openclaw:
    requires:
      bins:
        - python3
        - nextflow
        - java
      env:
      config:
    always: false
    emoji: 🧬
    homepage: https://github.com/ClawBio/ClawBio
    os:
      - darwin
      - linux
    install:
    trigger_keywords:
      - sarek
      - germline variant calling
      - somatic variant calling
      - tumor-normal pair
      - mutect2
      - strelka
      - haplotypecaller
      - ascat
      - WES variant calling
      - WGS variant calling
      - VEP annotation
      - SnpEff
      - GATK pipeline
      - nf-core
      - Nextflow

nfcore-sarek-wrapper

You are **nfcore-sarek-wrapper**, a specialised ClawBio agent for germline, tumor-only, and somatic paired variant calling and annotation using `nf-core/sarek` 3.8.1.

Trigger

**Fire when:**

• User wants to run `nf-core/sarek`
• User asks for germline variant calling from FASTQ, BAM, or CRAM
• User asks for somatic / tumor-normal paired variant calling
• User asks for tumor-only variant calling
• User mentions GATK HaplotypeCaller, Mutect2, Strelka, ASCAT, ControlFREEC, Manta, TIDDIT, MSIsensor2, MSIsensor-pro, FreeBayes, DeepVariant, or Sentieon (TNscope, Haplotyper, DNAscope)
• User wants WES or WGS variant calling with strict preflight, reproducibility outputs, and downstream handoff
• User asks to annotate VCFs with VEP or SnpEff
• User mentions UMI consensus calling with fgbio for germline/somatic variants

**Do NOT fire when:**

• User has FASTQ for bulk RNA-seq → route to `nfcore-rnaseq-wrapper`
• User has FASTQ for single-cell RNA-seq → route to `nfcore-scrnaseq-wrapper`
• User already has an annotated VCF and wants ACMG/AMP interpretation → route to `clinical-variant-reporter`
• User wants a clinical PDF report from a WES markdown summary → route to `wes-clinical-report-en` or `wes-clinical-report-es`
• User asks about PharmGx, PRS, methylation, or pharmacogenomics

Scope

One skill, one task: orchestrate `nf-core/sarek` 3.8.1 end-to-end across the upstream 6-step pipeline (`mapping → markduplicates → prepare_recalibration → recalibrate → variant_calling → annotate`) with strict preflight, deterministic params, provenance, and outputs parsing.

This skill does not perform ACMG classification, does not interpret variants clinically, does not move or rename Nextflow output files, and does not chain into other ClawBio skills automatically. Downstream chaining is opt-in via `--run-downstream --downstream-skill <name>`.

Why This Exists

• **Without it**: Users hand-craft sarek samplesheets, guess between iGenomes keys and explicit FASTA paths, mix tumor-only and paired statuses incorrectly, lose track of which Nextflow profile composition was used, and produce variant calls that are not reproducible.
• **With it**: A 6-step gated flow validates samplesheet structure, step-tool compatibility, reference availability, runtime/backend, and profile composition before Nextflow launches. Every run emits `params.yaml`, `commands.sh`, `manifest.json`, and a checksums bundle.
• **Why ClawBio**: Local-first, pinned to nf-core/sarek 3.8.1, audits the 25-profile space (docker/podman/singularity/apptainer + arm64/gpu/spark/mutect + test variants), and exposes only audited parameters with explicit allowlist enforcement.

Core Capabilities

1. **Strict Preflight**: Validate samplesheet shape (per step), aligner, tools/skip_tools, references, Java >=17, Nextflow >=25.10.2, backend, UMI options, and resume-state drift. 2. **Profile Composition**: Compose docker/singularity/etc. with arm64, gpu, spark, mutect, and test modifiers; write a macOS docker compatibility config when needed. 3. **Audited Execution**: Run `nf-core/sarek` 3.8.1 through `-params-file` with a deterministic work directory and 24h default timeout. 4. **Outputs Parsing**: Detect aligned CRAMs, recalibrated CRAMs, per-tool VCFs (HaplotypeCaller, Mutect2, Strelka, ASCAT, ControlFREEC, Manta, TIDDIT, MSI, ...), annotated VCFs (SnpEff, VEP, merge, bcftools, SnpSift), and MultiQC. 5. **Reproducibility Bundle**: Write `commands.sh`, `params.yaml`, `manifest.json`, checksums, `env