This skill should be used when the user asks to "build a genomics pipeline", "call variants", "analyze RNA-seq", "run ChIP-seq analysis", "annotate variants", "QC sequencing data", "detect CNVs", or when writing any bioinformatics pipeline code involving NGS data. Provides expert guidance on pipeline frameworks (Nextflow, Snakemake, WDL), alignment, variant calling, and production-ready nf-core workflows.
This skill should be used when the user asks to "build a genomics pipeline", "call variants", "analyze RNA-seq", "run ChIP-seq analysis", "annotate variants", "QC sequencing data", "detect CNVs", or when writing any bioinformatics pipeline code involving NGS data. Provides expert guidance on pipeline frameworks (Nextflow, Snakemake, WDL), alignment, variant calling, and production-ready nf-core workflows.
Genomics Pipeline Skill
Opinionated Defaults
Use Nextflow (nf-core ecosystem) for all new pipelines. For HPC-only environments without container support, use Snakemake instead.
Alignment
DNA short reads: Use BWA-MEM2
RNA-seq: Use STAR (splice-aware)
Long reads (ONT/PacBio): Use Minimap2
Variant Calling
Germline SNV/indel: Use DeepVariant (most accurate). GATK HaplotypeCaller if GATK ecosystem is required.
Somatic variants: Use Mutect2 (tumor/normal pairs)
Structural variants: Use Manta (Illumina). Add GRIDSS for complex SVs.
Annotation
Use VEP (Ensembl) as the primary annotator. Use SnpEff as a lightweight alternative for quick checks.
File Formats
FASTQ: Raw reads (always gzip compressed: .fastq.gz)
BAM/CRAM: Aligned reads — prefer CRAM over BAM (30-50% smaller)
VCF/BCF: Variant calls — always use bgzip + tabix for indexing
BED: Genomic intervals
GTF/GFF: Gene annotations
Always use indexed files (.bai, .crai, .tbi, .csi). Validate files before downstream analysis.
