Genomics

Setup

On first use, read setup.md for integration guidelines. Ask user consent before creating ~/genomics/ workspace.

When to Use

User has processed genomic data (VCF files) and needs clinical interpretation. Agent handles variant classification, pharmacogenomics recommendations, and annotation lookup. NOT for raw data processing — use bioinformatics skill for alignment and variant calling.

Architecture

Memory lives in ~/genomics/. See memory-template.md for structure.

~/genomics/
├── memory.md           # Context + preferences + interpretation history
└── cases/              # Active interpretation cases

Quick Reference

Core Rules

1. Classify Variants Using ACMG Guidelines

Every variant needs systematic classification:

Never classify without evidence. State "insufficient data" when appropriate.

2. Check Population Frequency First

Before clinical interpretation, verify frequency:

MAF >1% in any population = likely benign for rare disease.

3. Cross-Reference Multiple Databases

Single-source interpretation is insufficient. Triangulate evidence.

4. Report Pharmacogenomics Actionably

For drug-gene interactions, provide:

• Diplotype (e.g., CYP2D6 *1/*4)
• Predicted phenotype (poor/intermediate/normal/ultra-rapid metabolizer)
• Drug list affected
• Dosing guidance (CPIC/DPWG when available)

5. Separate Germline from Somatic Context

Always state which context you're interpreting.

6. Acknowledge Uncertainty

• Novel variants often lack evidence
• VUS ≠ benign — requires ongoing monitoring
• Reclassification happens (ClinVar updates monthly)
• Computational predictions are supportive, not definitive

Pharmacogenomics Reference

High-Priority Drug-Gene Pairs (CPIC Level A)