--- name: drug-targets description: | Causal drug-target and mechanism gene prioritization from public source records, drugs, drug classes, mechanisms, and candidate gene lists. tools: - phenotype.retrieve_disease_drug_targets - phenotype.compare_drug_target_evidence - research.list_sources - research.record - research.query - research.search mutating: true --- # Drug Targets Use this skill for disease-scoped clinical drug-target retrieval, direct drug-target records, PharmaProjects-style target context, ChEMBL mechanism genes, DrugBank target context, or candidate-gene review for a drug, drug class, or mechanism. ## Contract - Direct drug-target or mechanism evidence outranks target-disease association scores and GWAS-style association. - ChEMBL, DrugBank, and PharmaProjects-style records can support direct target claims when the source supports both the gene and the drug, class, mechanism, or indication context. - Open Targets association context is useful for review; direct drug-target evidence comes from source records that support the drug, class, or mechanism relationship. - Open Targets disease drug and clinical candidate records can retrieve disease-scoped clinical drug-target genes when the drug target comes from a mechanism-of-action row. - Treat returned rankings as source evidence. The agent decides whether the drug-target prior matches the question. When using cross-source comparison, use `prior_fit` before reading a panel as task-relevant and audit `decision_evidence` before answering. ## Tool Flow 1. `phenotype.retrieve_disease_drug_targets` retrieves Open Targets clinical drug candidate target genes for a supplied disease anchor. 2. `phenotype.compare_drug_target_evidence` compares candidate genes against direct drug-side context: drug, drug class, or mechanism. 3. If source support is missing, use `research.list_sources` to choose direct target sources, review them, and store narrow findings with `research.record`. 4. Re-run the same selected tool after recording reviewed findings. Example: - `phenotype.retrieve_disease_drug_targets` with `{"disease":"asthma","genes":["ADRB2","IL13"]}` - `phenotype.compare_drug_target_evidence` with `{"drug_class":"beta agonist","phenotype":"asthma","genes":["ADRB2","IL13"],"source_records":[{"genes":["ADRB2"],"drug_class":"beta agonist","verified_fields":{"genes":["ADRB2"],"drug_class":"beta agonist"},"support_spans":[{"field":"genes","text":"source-backed ADRB2 text"}]}]}` ## Source Records Prefer source records with: - `genes`: candidate target genes named by the source. - `drug`, `drug_class`, `indication`, or `mechanism`. - `source_title`, `source_url`, and `source_type`. - `finding` or `text`: short source-backed finding. - `verified_fields` and `support_spans` showing where the source supports the gene and drug-target or mechanism context. ## Answering Use a direct gene-symbol answer only when reviewed evidence supports the drug-target or mechanism relationship requested by the question. Otherwise state the source gap and summarize the strongest reviewed evidence without presenting it as the final target. ## 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.compare_drug_target_evidence Compare candidate genes using direct drug-target or mechanism evidence only. **Use when**: Returns direct drug-target, target-mechanism, ChEMBL, DrugBank, or PharmaProjects evidence for candidate genes. **Why necessary**: Drug-target questions require direct target/mechanism evidence, which is distinct from disease association evidence. **Result semantics**: Returns source-local drug-target evidence only; association-only evidence cannot create direct target support. ### phenotype.retrieve_disease_drug_targets Retrieve disease-scoped clinical drug-target genes from Open Targets drug candidate records. **Use when**: Returns Open Targets clinical drug candidate target genes for a supplied disease anchor, with optional gene_membership projection for supplied candidate genes. **Why necessary**: Clinical drug-target records answer therapeutic-target membership without implying causal genetics or treatment efficacy. **Result semantics**: Returns disease-scoped clinical drug-target records and source-local ordering; the host agent decides how they apply. mode='gene_membership' projects the same source records into per-gene membership booleans and highest observed phase for supplied genes. Does not ingest agent-supplied evidence and does not infer treatment efficacy or final causal-gene answers.