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.

Outcome-Shaped Questions

Outcome-shaped questions ("will I get X?", "am I at higher risk for X?", "how likely am I to X?", "will I go bald?") are answered by combining capabilities that contribute orthogonal evidence to the same question. The combination is question-dependent.

Answer Contract

User-facing answers must include:

• The evidence classes used: sample observation, ClinVar/static source, population frequency, GWAS association, reviewed source, or limitation.
• Whether Active Genome Index evidence changed the result, limitation, blocker, or next action when that is material to the answer.
• The candidate evidence basis when present: source prior, direct versus adjacent or plausibility-only support, and any warnings.
• What matters for decision-making: answer support, genotype support, callability, source review, clinical confirmation, or user/clinical context.

Use informational medical language. Clinical decisions need clinician confirmation. Personal risk percentages need cited source support. External services receive selected public targets only.

Intent Checks

• Use source intake for questions that provide or require a genome source file.
• Resolve intent as the host agent using this skill pack and tool metadata.
• Treat session-selected source Active Genome Index records or Active Genome Index records as the Active Genome Index.
• Keep answers from public sources clear without adding a routine "no Active Genome Index" disclaimer.
• Use narrow variant/source tools for small factual lookups.

Cross-Capability Synthesis

A scope-limited result from this capability is not a final user-facing answer when other Genomi capabilities can contribute orthogonal evidence to the same question. Returning "cannot answer" while applicable capabilities remain unexamined is a host-agent failure mode.

Tools

phenotype.retrieve_trait_gene_records

Retrieve native trait-to-gene records from integrated public sources, optionally filtered to gene symbols.

Use when: Retrieves trait-to-gene records from Open Targets target-disease associations and disease clinical drug candidate records. The genes array is an optional filter, not the scope of the capability.

Why necessary: Trait-to-gene retrieval supplies native public records for complex traits without pretending to rank final causal genes.

Result semantics: Returns native retrieved source records grouped by gene and evidence regime; it does not return a recommended answer. Association-only records are labelled as association_only_not_causal. A clean empty result means the declared sources had no matching trait-to-gene records for the input trait and optional gene filter.