Genomic Inquiry

Genomic Inquiry

Use this skill as the default entry for natural-language DNA questions: personal triage, "what matters in my genome?", "do I have this variant?", variant/gene interpretation, GWAS-style questions, or public genomic background.

Goal

Turn the user's question into the smallest useful evidence action. A genome source is optional context. Use the Active Genome Index when present and relevant; with public-only context, answer from public sources, GWAS, and shared reviewed evidence.

Convention: See skills/conventions/context-routing.md before selecting Active Genome Index. Convention: See skills/conventions/evidence-quality.md before making personal or medical claims.

Contract

Contract:

• User intent drives the selected evidence path.
• The host agent resolves intent from this skill pack and tool outputs.
• Personal claims use only explicitly selected session context.
• Public-source answers do not need a routine Active Genome Index status line.
• Tool outputs are inspected before choosing additional operations.
• Operation metadata and focused skills guide tool choice; tool results are evidence for the host agent to interpret.
• Candidate and ranking tools return evidence views, alternatives, warnings, coverage, and source-prior detail for the host agent to interpret.

Agent Start

1. Use genomi.describe_context when the Active Genome Index is unknown.
2. Extract obvious fields from the user request: source, agi_id, user/profile nickname, rsid, gene, exact allele, phenotype, drug, condition, or topic.
3. Load the most specific focused capability skill, then call its capability tools through genomi.invoke.
4. Call one narrow tool and inspect its output before selecting additional evidence operations.

Personal Source Triage

For "what matters in my genome?" or similar broad personal questions:

• If a source path is supplied, build/select it with genomi.parse_source when an Active Genome Index is needed. The supplied source path is approval to read that source for this session.
• Run clinvar.scan_candidates to build a deterministic ClinVar candidate inventory. If the build-specific ClinVar library is missing, ask before installing clinvar-grch38 or clinvar-grch37.
• Inspect structured candidate guidance before selecting findings for follow-up or final interpretation.
• Drill into selected findings with variant.gather_allele_context, variant.gather_gene_context, active_genome_index.classify_genotype_support, or active_genome_index.classify_region_callability.

Group raw matches by actionability, clinical assertion strength, uncertainty/conflict, carrier context, common-risk or trait context, and limitations.

After genomi.parse_source, use the Active Genome Index for normal future inquiries. Surface the original intake file path for rebuild or validation work.

Specific Questions

• Personal rsID question with an Active Genome Index: use variant.resolve first.
• Personal exact allele question: use active_genome_index.classify_genotype_support and variant.gather_allele_context when allele support and source context are needed.
• Gene-level sample question: use variant.gather_gene_context and only make sample-specific statements for observed/sample-supported variants.
• Absence/reference claims require active_genome_index.classify_region_callability.
• Public variant/gene question with public-only context: use research.list_sources, research.build_target_packet, focused source review, and research.record when useful.
• Candidate genes: use the source-specific tool when the source family is clear: phenotype.compare_gene_hpo_evidence for HPO or single-subject phenotype matching, gwas.compare_gene_associations for explicit GWAS Catalog reported_gene/mapped_gene/source gene-field evidence, and phenotype.compare_drug_target_evidence for drug-target or mechanism evidence. phenotype.retrieve_trait_gene_records retrieves trait-to-gene records from integrated public sources and can be filtered by candidate genes. If several source families could answer the question, call the relevant source-specific tools separately and keep their evidence priors separate in the answer. GWAS Catalog mapped genes are not causal-gene assignments, and association_only_not_causal records cannot be the final support for a causal-gene answer.
• Analytical grounding: use pathway.retrieve_members for Reactome, KEGG, or Hallmark pathway member genes; cell_type.retrieve_markers for HPA, CellMarker, PanglaoDB, or ENCODE marker sources; and region.retrieve_features for local GENCODE/ENCODE interval overlaps.
• GWAS phenotype plus candidate rsIDs: load the GWAS Catalog skill, call gwas.compare_variant_associations, then select additional operations from the returned evidence. Variant lookup, ClinVar, Mendelian, sample, same-gene, or pathway context is follow-up context to report beside the population-trait GWAS Catalog rsID ranking.
• Functional-genomics perturbation context plus candidate genes: load the functional genomics skill, call functional_genomics.compare_gene_perturbation for the normal native-retrieve, verify, and compare flow, and answer from verified perturbation-source evidence rather than generic co-mention.