- GWAS-to-Drug Target Discovery
- Transform genome-wide association studies (GWAS) into actionable drug targets and repurposing opportunities.
- IMPORTANT
-
- Always use English terms in tool calls. Respond in the user's language.
- Overview
- This skill bridges genetic discoveries from GWAS with drug development by:
- Identifying genetic risk factors
- - Finding genes associated with diseases
- Assessing druggability
- - Evaluating which genes can be targeted by drugs
- Prioritizing targets
- - Ranking candidates by genetic evidence strength
- Finding existing drugs
- - Discovering approved/investigational compounds
- Identifying repurposing opportunities
- - Matching drugs to new indications
- Key insight
-
- Targets with genetic support have 2x higher probability of clinical approval (Nelson et al., Nature Genetics 2015).
- Workflow Steps
- Step 1: GWAS Gene Discovery
- Input
-
- Disease/trait name (e.g., "type 2 diabetes", "Alzheimer disease")
- Process
-
- Query GWAS Catalog for associations, filter by significance (p < 5x10^-8), map variants to genes, aggregate evidence.
- Tools
- :
- gwas_get_associations_for_trait
- - Get associations by disease
- gwas_search_associations
- - Flexible search
- gwas_get_associations_for_snp
- - SNP-specific associations
- OpenTargets_search_gwas_studies_by_disease
- - Curated GWAS data
- OpenTargets_get_variant_credible_sets
- - Fine-mapped loci with L2G predictions
- Step 2: Druggability Assessment
- Input
-
- Gene list from Step 1
- Process
-
- Check target class, assess tractability, evaluate safety, check for tool compounds or structures.
- Tools
- :
- OpenTargets_get_target_tractability_by_ensemblID
- - Druggability assessment
- OpenTargets_get_target_classes_by_ensemblID
- - Target classification
- OpenTargets_get_target_safety_profile_by_ensemblID
- - Safety data
- OpenTargets_get_target_genomic_location_by_ensemblID
- - Genomic context
- Step 3: Target Prioritization
- Scoring Formula
- :
- Target Score = (GWAS Score x 0.4) + (Druggability x 0.3) + (Clinical Evidence x 0.2) + (Novelty x 0.1)
- Rank targets by composite score. Generate target dossiers.
- Step 4: Existing Drug Search
- Process
- Search drug-target associations, find approved drugs and clinical candidates, get MOA and indication data. Tools : OpenTargets_get_associated_drugs_by_disease_efoId - Known drugs for disease OpenTargets_get_drug_mechanisms_of_action_by_chemblId - Drug MOA ChEMBL_get_target_activities - Bioactivity data ChEMBL_get_drug_mechanisms / ChEMBL_search_drugs - Drug data Step 5: Clinical Evidence & Safety Tools : FDA_get_adverse_reactions_by_drug_name - Safety data FDA_get_active_ingredient_info_by_drug_name - Drug composition OpenTargets_get_drug_warnings_by_chemblId - Drug warnings Step 6: Repurposing Opportunities Match drug targets to new disease genes, assess mechanistic fit, check contraindications, estimate repurposing probability. Quick Start from tooluniverse import ToolUniverse tu = ToolUniverse ( use_cache = True ) tu . load_tools ( )
Step 1: Get GWAS associations
associations
tu . tools . gwas_get_associations_for_trait ( trait = "type 2 diabetes" )
Step 2: Assess druggability
tractability
tu . tools . OpenTargets_get_target_tractability_by_ensemblID ( ensemblID = "ENSG00000148737" )
Step 3: Find existing drugs
drugs
- tu
- .
- tools
- .
- OpenTargets_get_associated_drugs_by_disease_efoId
- (
- efoId
- =
- "EFO_0001360"
- )
- All Tools by Category
- GWAS & Genetics
- :
- gwas_get_associations_for_trait
- /
- gwas_search_associations
- /
- gwas_get_associations_for_snp
- OpenTargets_search_gwas_studies_by_disease
- /
- OpenTargets_get_variant_credible_sets
- Target Assessment
- :
- OpenTargets_get_target_tractability_by_ensemblID
- /
- OpenTargets_get_target_classes_by_ensemblID
- OpenTargets_get_target_safety_profile_by_ensemblID
- /
- OpenTargets_get_target_genomic_location_by_ensemblID
- Drug Discovery
- :
- OpenTargets_get_associated_drugs_by_disease_efoId
- /
- OpenTargets_get_drug_mechanisms_of_action_by_chemblId
- ChEMBL_get_target_activities
- /
- ChEMBL_get_drug_mechanisms
- /
- ChEMBL_search_drugs
- Safety & Clinical
- :
- FDA_get_adverse_reactions_by_drug_name
- /
- FDA_get_active_ingredient_info_by_drug_name
- OpenTargets_get_drug_warnings_by_chemblId
- Literature
- :
- PubMed_search_articles
- /
- EuropePMC_search_articles
- /
- ClinicalTrials_search
- Best Practices
- Multi-ancestry GWAS
-
- Include trans-ethnic meta-analyses for robust signals
- Functional validation
-
- Confirm with eQTL, pQTL, colocalization analysis
- Network analysis
-
- Group GWAS hits by pathway (KEGG, Reactome)
- Safety assessment
-
- Check gnomAD pLI, GTEx expression, PharmaGKB
- Batch operations
- Use tu.run_batch() for parallel queries across targets Troubleshooting Problem Solution No GWAS hits for disease Try broader trait name, check synonyms, use OpenTargets Gene not in druggable class Consider antibody/antisense modalities, check pathway neighbors No existing drugs for target Target may be novel - check tool compounds in ChEMBL Low L2G score Variants may be regulatory - check eQTL/pQTL evidence Reference Files REFERENCE.md - Detailed concepts, druggability tiers, clinical translation, limitations, ethics EXAMPLES.md - Use cases (Huntington's, Alzheimer's, diabetes) with success stories REPORT_TEMPLATE.md - Output report template with scoring criteria PROCEDURES.md - Step-by-step implementation procedures QUICK_START.md - Quick start guide