Opentargets Database

This skill should be used when:

• Target discovery: Finding potential therapeutic targets for a disease
• Target assessment: Evaluating tractability, safety, and druggability of genes
• Evidence gathering: Retrieving supporting evidence for target-disease associations
• Drug repurposing: Identifying existing drugs that could be repurposed for new indications
• Competitive intelligence: Understanding clinical precedence and drug development landscape
• Target prioritization: Ranking targets based on genetic evidence and other data types
• Mechanism research: Investigating biological pathways and gene functions
• Biomarker discovery: Finding genes differentially expressed in disease
• Safety assessment: Identifying potential toxicity concerns for drug targets

Core Workflow

1. Search for Entities

Start by finding the identifiers for targets, diseases, or drugs of interest.

2. Query Target Information

Retrieve comprehensive target annotations to assess druggability and biology.

Key annotations to review:

• Tractability: Small molecule, antibody, PROTAC druggability predictions
• Safety: Known toxicity concerns from multiple databases
• Genetic constraint: pLI and LOEUF scores indicating essentiality
• Disease associations: Diseases linked to the target with evidence scores

3. Query Disease Information

Get disease details and associated targets/drugs.

4. Retrieve Target-Disease Evidence

Get detailed evidence supporting a target-disease association.

Major evidence types:

1. genetic_association: GWAS, rare variants, ClinVar, gene burden
2. somatic_mutation: Cancer Gene Census, IntOGen, cancer biomarkers
3. known_drug: Clinical precedence from approved/clinical drugs
4. affected_pathway: CRISPR screens, pathway analyses, gene signatures
5. rna_expression: Differential expression from Expression Atlas
6. animal_model: Mouse phenotypes from IMPC
7. literature: Text-mining from Europe PMC

Refer to references/evidence_types.md for detailed descriptions of all evidence types and interpretation guidelines.

5. Find Known Drugs

Identify drugs used for a disease and their targets.

Clinical phases:

• Phase 4: Approved drug
• Phase 3: Late-stage clinical trials
• Phase 2: Mid-stage trials
• Phase 1: Early safety trials

6. Get Drug Information

Retrieve detailed drug information including mechanisms and indications.

7. Get All Associations for a Target

Find all diseases associated with a target, optionally filtering by score.

Association scores:

• Range: 0-1 (higher = stronger evidence)
• Aggregate evidence across all data types using harmonic sum
• NOT confidence scores but relative ranking metrics
• Under-studied diseases may have lower scores despite good evidence

Best Practices

Target Prioritization Strategy

When prioritizing drug targets:

1. Start with genetic evidence: Human genetics (GWAS, rare variants) provides strongest disease relevance
2. Check tractability: Prefer targets with clinical or discovery precedence
3. Assess safety: Review safety liabilities, expression patterns, and genetic constraint
4. Evaluate clinical precedence: Known drugs indicate druggability and therapeutic window
5. Consider multiple evidence types: Convergent evidence from different sources increases confidence
6. Validate mechanistically: Pathway evidence and biological plausibility
7. Review literature manually: For critical decisions, examine primary publications

Evidence Interpretation

Strong evidence indicators:

• Multiple independent evidence sources
• High genetic association scores (especially GWAS with L2G > 0.5)
• Clinical precedence from approved drugs
• ClinVar pathogenic variants with disease match
• Mouse models with relevant phenotypes

Caution flags:

• Single evidence source only
• Text-mining as sole evidence (requires manual validation)
• Conflicting evidence across sources
• High essentiality + ubiquitous expression (poor therapeutic window)
• Multiple safety liabilities

Score interpretation:

• Scores rank relative strength, not absolute confidence
• Under-studied diseases have lower scores despite potentially valid targets
• Weight expert-curated sources higher than computational predictions
• Check evidence breakdown, not just overall score

Common Workflows

Workflow 1: Target Discovery for a Disease

1. Search for disease → get EFO ID
2. Query disease info with include_targets=True
3. Review top targets sorted by association score
4. For promising targets, get detailed target info
5. Examine evidence types supporting each association
6. Assess tractability and safety for prioritized targets

Workflow 2: Target Validation

1. Search for target → get Ensembl ID
2. Get comprehensive target info
3. Check tractability (especially clinical precedence)
4. Review safety liabilities and genetic constraint
5. Examine disease associations to understand biology
6. Look for chemical probes or tool compounds
7. Check known drugs targeting gene for mechanism insights

Workflow 3: Drug Repurposing

1. Search for disease → get EFO ID
2. Get known drugs for disease
3. For each drug, get detailed drug info
4. Examine mechanisms of action and targets
5. Look for related disease indications
6. Assess clinical trial phases and status
7. Identify repurposing opportunities based on mechanism

Workflow 4: Competitive Intelligence

1. Search for target of interest
2. Get associated diseases with evidence
3. For each disease, get known drugs
4. Review clinical phases and development status
5. Identify competitors and their mechanisms
6. Assess clinical precedence and market landscape

Resources

Scripts

scripts/query_opentargets.py Helper functions for common API operations:

• search_entities() - Search for targets, diseases, or drugs
• get_target_info() - Retrieve target annotations
• get_disease_info() - Retrieve disease information
• get_target_disease_evidence() - Get supporting evidence
• get_known_drugs_for_disease() - Find drugs for a disease
• get_drug_info() - Retrieve drug details
• get_target_associations() - Get all associations for a target
• execute_query() - Execute custom GraphQL queries

References

references/api_reference.md Complete GraphQL API documentation including:

• Endpoint details and authentication
• Available query types (target, disease, drug, search)
• Example queries for all common operations
• Error handling and best practices
• Data licensing and citation requirements

references/evidence_types.md Comprehensive guide to evidence types and data sources:

• Detailed descriptions of all 7 major evidence types
• Scoring methodologies for each source
• Evidence interpretation guidelines
• Strengths and limitations of each evidence type
• Quality assessment recommendations

references/target_annotations.md Complete target annotation reference:

• 12 major annotation categories explained
• Tractability assessment details
• Safety liability sources
• Expression, essentiality, and constraint data
• Interpretation guidelines for target prioritization
• Red flags and green flags for target assessment

Data Updates and Versioning

The Open Targets Platform is updated quarterly with new data releases. The current release (as of October 2025) is available at the API endpoint.

Release information: Check https://platform-docs.opentargets.org/release-notes for the latest updates.

Citation: When using Open Targets data, cite: Ochoa, D. et al. (2025) Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research, 53(D1):D1467-D1477.

Limitations and Considerations

1. API is for exploratory queries: For systematic analyses of many targets/diseases, use data downloads or BigQuery
2. Scores are relative, not absolute: Association scores rank evidence strength but don't predict clinical success
3. Under-studied diseases score lower: Novel or rare diseases may have strong evidence but lower aggregate scores
4. Evidence quality varies: Weight expert-curated sources higher than computational predictions
5. Requires biological interpretation: Scores and evidence must be interpreted in biological and clinical context
6. No authentication required: All data is freely accessible, but cite appropriately