Comprehensive computational validation of drug targets for early-stage drug discovery. Evaluates targets across 10 dimensions (disambiguation, disease association, druggability, chemical matter, clinical precedent, safety, pathway context, validation evidence, structural insights, validation roadmap) using 60+ ToolUniverse tools. Produces a quantitative Target Validation Score (0-100) with GO/NO-GO recommendation. Use when users ask about target validation, druggability assessment, target prioritization, or "is X a good drug target for Y?"
Validate drug target hypotheses using multi-dimensional computational evidence before committing to wet-lab work. Produces a quantitative Target Validation Score (0-100) with priority tier classification and GO/NO-GO recommendation.
Apply when users ask about:
Not for (use other skills): general target biology (tooluniverse-target-research), drug compound profiling (tooluniverse-drug-research), variant interpretation (tooluniverse-variant-interpretation), disease research (tooluniverse-disease-research).
| Parameter | Required | Description | Example |
|---|---|---|---|
| target | Yes | Gene symbol, protein name, or UniProt ID | EGFR, P00533 |
| disease | No | Disease/indication for context | Non-small cell lung cancer |
| modality | No | Preferred therapeutic modality | small molecule, antibody, PROTAC |
Total: 0-100 points across 5 dimensions (details in SCORING_CRITERIA.md):
| Dimension | Max | Sub-dimensions |
|---|---|---|
| Disease Association | 30 | Genetic (10) + Literature (10) + Pathway (10) |
| Druggability | 25 | Structure (10) + Chemical matter (10) + Target class (5) |
| Safety Profile | 20 | Expression (5) + Genetic validation (10) + ADRs (5) |
| Clinical Precedent | 15 | Based on highest clinical stage achieved |
| Validation Evidence | 10 | Functional studies (5) + Disease models (5) |
Priority Tiers: 80-100 = Tier 1 (GO) | 60-79 = Tier 2 (CONDITIONAL GO) | 40-59 = Tier 3 (CAUTION) | 0-39 = Tier 4 (NO-GO)
Evidence Grades: T1 (clinical proof) > T2 (functional studies) > T3 (associations) > T4 (predictions)
Resolve target to ALL identifiers before any analysis.
Steps:
MyGene_query_genes - Get initial IDs (Ensembl, UniProt, Entrez)ensembl_lookup_gene - Get versioned Ensembl ID (species="homo_sapiens" REQUIRED)ensembl_get_xrefs - Cross-references (HGNC, etc.)OpenTargets_get_target_id_description_by_name - Verify OT targetChEMBL_search_targets - Get ChEMBL target IDUniProt_get_function_by_accession - Function summary (returns list of strings)UniProt_get_alternative_names_by_accession - Collision detectionOutput: Table of verified identifiers (Gene Symbol, Ensembl, UniProt, Entrez, ChEMBL, HGNC) plus protein function and target class.
Quantify target-disease association from genetic, literature, and pathway evidence.
Key tools:
OpenTargets_get_diseases_phenotypes_by_target_ensembl - Disease associationsOpenTargets_target_disease_evidence - Detailed evidence (needs efoId + ensemblId)OpenTargets_get_evidence_by_datasource - Evidence by data sourcegwas_get_snps_for_gene / gwas_search_studies - GWAS evidencegnomad_get_gene_constraints - Genetic constraint (pLI, LOEUF)PubMed_search_articles - Literature (returns plain list of dicts)OpenTargets_get_publications_by_target_ensemblID - OT publications (uses entityId)Assess whether the target is amenable to therapeutic intervention.
Key tools:
OpenTargets_get_target_tractability_by_ensemblID - Tractability (SM, AB, PR, OC)OpenTargets_get_target_classes_by_ensemblID - Target classificationPharos_get_target - TDL: Tclin > Tchem > Tbio > TdarkDGIdb_get_gene_druggability - Druggability categoriesalphafold_get_prediction (param: qualifier) / alphafold_get_summaryProteinsPlus_predict_binding_sites - Pocket detectionOpenTargets_get_chemical_probes_by_target_ensemblID - Chemical probesOpenTargets_get_target_enabling_packages_by_ensemblID - TEPsIdentify existing chemical starting points for target validation.
Key tools:
ChEMBL_search_targets + ChEMBL_get_target_activities - Bioactivity data (note: target_chembl_id__exact with double underscore)BindingDB_get_ligands_by_uniprot - Binding data (affinity in nM)PubChem_search_assays_by_target_gene + PubChem_get_assay_active_compounds - HTS dataOpenTargets_get_associated_drugs_by_target_ensemblID - Known drugs (size REQUIRED)ChEMBL_search_mechanisms - Drug mechanismsDGIdb_get_gene_info - Drug-gene interactionsAssess clinical validation from approved drugs and clinical trials.
Key tools:
FDA_get_mechanism_of_action_by_drug_name / FDA_get_indications_by_drug_namedrugbank_get_targets_by_drug_name_or_drugbank_id (ALL params required: query, case_sensitive, exact_match, limit)search_clinical_trials (query_term REQUIRED)OpenTargets_get_drug_warnings_by_chemblId / OpenTargets_get_drug_adverse_events_by_chemblIdIdentify safety risks from expression, genetics, and known adverse events.
Key tools:
OpenTargets_get_target_safety_profile_by_ensemblID - Safety liabilitiesGTEx_get_median_gene_expression - Tissue expression (operation="median" REQUIRED)HPA_search_genes_by_query / HPA_get_comprehensive_gene_details_by_ensembl_idOpenTargets_get_biological_mouse_models_by_ensemblID - KO phenotypesFDA_get_adverse_reactions_by_drug_name / FDA_get_boxed_warning_info_by_drug_nameOpenTargets_get_target_homologues_by_ensemblID - Paralog risksCritical tissues to check: heart, liver, kidney, brain, bone marrow.
Understand the target's role in biological networks and disease pathways.
Key tools:
Reactome_map_uniprot_to_pathways (param: id, NOT uniprot_id)STRING_get_protein_interactions (param: protein_ids as array, species=9606)intact_get_interactions - Experimental PPIOpenTargets_get_target_gene_ontology_by_ensemblID - GO termsSTRING_functional_enrichment - Enrichment analysisAssess: pathway redundancy, compensation risk, feedback loops.
Assess existing functional validation data.
Key tools:
DepMap_get_gene_dependencies - Essentiality (score < -0.5 = essential)PubMed_search_articles - Search for CRISPR/siRNA/knockout studiesCTD_get_gene_diseases - Gene-disease associationsLeverage structural biology for druggability and mechanism understanding.
Key tools:
UniProt_get_entry_by_accession - Extract PDB cross-referencesget_protein_metadata_by_pdb_id / pdbe_get_entry_summary / pdbe_get_entry_qualityalphafold_get_prediction / alphafold_get_summary - pLDDT confidenceProteinsPlus_predict_binding_sites - Druggable pocketsInterPro_get_protein_domains / InterPro_get_domain_details - Domain architectureComprehensive collision-aware literature analysis.
Steps:
"{gene_symbol}"[Title] in PubMed; if >20% off-topic, add filters (AND protein OR gene OR receptor)review[pt] filter in PubMedopenalex_search_works for impact dataEuropePMC_search_articlesSynthesize all phases into actionable output:
Create file: [TARGET]_[DISEASE]_validation_report.md
Use the full template from REPORT_TEMPLATE.md. Key sections:
Complete the Completeness Checklist (in REPORT_TEMPLATE.md) before finalizing to verify all phases were covered, all scores justified, and negative results documented.