@bgicli/bgicli 2.1.1 → 2.2.0

package/data/skills/tooluniverse-drug-repurposing/SKILL.md

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+---
+name: tooluniverse-drug-repurposing
+description: Identify drug repurposing candidates using ToolUniverse for target-based, compound-based, and disease-driven strategies. Searches existing drugs for new therapeutic indications by analyzing targets, bioactivity, safety profiles, and literature evidence. Use when exploring drug repurposing opportunities, finding new indications for approved drugs, or when users mention drug repositioning, off-label uses, or therapeutic alternatives.
+---
+
+# Drug Repurposing with ToolUniverse
+
+Systematically identify and evaluate drug repurposing candidates using multiple computational strategies.
+
+**IMPORTANT**: Always use English terms in tool calls (drug names, disease names, target names), even if the user writes in another language. Only try original-language terms as a fallback if English returns no results. Respond in the user's language.
+
+## Core Strategies
+
+### 1. Target-Based Repurposing
+Start with disease targets → Find drugs that modulate those targets
+
+### 2. Compound-Based Repurposing  
+Start with approved drugs → Find new disease indications
+
+### 3. Disease-Driven Repurposing
+Start with disease → Find targets → Match to existing drugs
+
+## Quick Start
+
+```python
+from tooluniverse import ToolUniverse
+
+tu = ToolUniverse(use_cache=True)
+tu.load_tools()
+
+# Example: Find repurposing candidates for a disease
+disease_name = "rheumatoid arthritis"
+
+# Step 1: Get disease information
+disease_info = tu.tools.OpenTargets_get_disease_id_description_by_name(
+    diseaseName=disease_name
+)
+
+# Step 2: Get associated targets
+disease_id = disease_info['data']['id']
+targets = tu.tools.OpenTargets_get_associated_targets_by_disease_efoId(
+    efoId=disease_id,
+    limit=10
+)
+
+# Step 3: Find drugs for each target
+for target in targets['data'][:5]:
+    drugs = tu.tools.DGIdb_get_drug_gene_interactions(
+        gene_name=target['gene_symbol']
+    )
+    # Evaluate each drug candidate...
+```
+
+## Complete Workflow
+
+### Phase 1: Disease & Target Analysis
+
+```python
+# 1.1 Get disease information
+disease_info = tu.tools.OpenTargets_get_disease_id_description_by_name(
+    diseaseName="[disease_name]"
+)
+
+# 1.2 Find associated targets
+targets = tu.tools.OpenTargets_get_associated_targets_by_disease_efoId(
+    efoId=disease_info['data']['id'],
+    limit=20
+)
+
+# 1.3 Get target details for top candidates
+target_details = []
+for target in targets['data'][:10]:
+    details = tu.tools.UniProt_get_entry_by_accession(
+        accession=target['uniprot_id']
+    )
+    target_details.append(details)
+```
+
+### Phase 2: Drug Discovery
+
+```python
+# 2.1 Find drugs targeting disease-associated targets
+drug_candidates = []
+
+for target in targets['data'][:10]:
+    # Search DrugBank
+    drugbank_results = tu.tools.drugbank_get_drug_name_and_description_by_target_name(
+        target_name=target['gene_symbol']
+    )
+    
+    # Search DGIdb
+    dgidb_results = tu.tools.DGIdb_get_drug_gene_interactions(
+        gene_name=target['gene_symbol']
+    )
+    
+    # Search ChEMBL
+    chembl_results = tu.tools.ChEMBL_search_drugs(
+        query=target['gene_symbol'],
+        limit=10
+    )
+    
+    drug_candidates.extend([drugbank_results, dgidb_results, chembl_results])
+
+# 2.2 Get drug details
+for drug_name in unique_drugs:
+    # Get DrugBank info
+    drug_info = tu.tools.drugbank_get_drug_basic_info_by_drug_name_or_id(
+        drug_name_or_drugbank_id=drug_name
+    )
+    
+    # Get current indications
+    indications = tu.tools.drugbank_get_indications_by_drug_name_or_drugbank_id(
+        drug_name_or_drugbank_id=drug_name
+    )
+    
+    # Get pharmacology
+    pharmacology = tu.tools.drugbank_get_pharmacology_by_drug_name_or_drugbank_id(
+        drug_name_or_drugbank_id=drug_name
+    )
+```
+
+### Phase 3: Safety & Feasibility Assessment
+
+```python
+# 3.1 Check FDA safety data
+for drug in top_candidates:
+    # Get warnings and precautions
+    warnings = tu.tools.FDA_get_warnings_and_cautions_by_drug_name(
+        drug_name=drug['name']
+    )
+    
+    # Get adverse event reports
+    adverse_events = tu.tools.FAERS_search_reports_by_drug_and_reaction(
+        drug_name=drug['name'],
+        limit=100
+    )
+    
+    # Get drug interactions
+    interactions = tu.tools.drugbank_get_drug_interactions_by_drug_name_or_id(
+        drug_name_or_id=drug['name']
+    )
+
+# 3.2 Assess ADMET properties (for novel formulations)
+for drug in top_candidates:
+    if 'smiles' in drug:
+        admet = tu.tools.ADMETAI_predict_admet(
+            smiles=drug['smiles'],
+            use_cache=True
+        )
+```
+
+### Phase 4: Literature Evidence
+
+```python
+# 4.1 Search for existing evidence
+for drug in top_candidates:
+    # PubMed search
+    query = f"{drug['name']} AND {disease_name}"
+    pubmed_results = tu.tools.PubMed_search_articles(
+        query=query,
+        max_results=50
+    )
+    
+    # Europe PMC search
+    pmc_results = tu.tools.EuropePMC_search_articles(
+        query=query,
+        limit=50
+    )
+    
+    # Clinical trials
+    trials = tu.tools.ClinicalTrials_search(
+        condition=disease_name,
+        intervention=drug['name']
+    )
+```
+
+### Phase 5: Scoring & Ranking
+
+Create a scoring function to rank candidates:
+
+```python
+def score_repurposing_candidate(drug, target_score, safety_data, literature_count):
+    """Score drug repurposing candidate (0-100)."""
+    score = 0
+    
+    # Target association strength (0-40 points)
+    score += min(target_score * 40, 40)
+    
+    # Safety profile (0-30 points)
+    if drug['approval_status'] == 'approved':
+        score += 20
+    elif drug['approval_status'] == 'clinical':
+        score += 10
+    
+    if not safety_data.get('black_box_warning'):
+        score += 10
+    
+    # Literature evidence (0-20 points)
+    score += min(literature_count / 5 * 20, 20)
+    
+    # Drug-likeness (0-10 points)
+    if drug.get('bioavailability') == 'high':
+        score += 10
+    
+    return score
+
+# Score all candidates
+scored_candidates = []
+for drug in drug_candidates:
+    score = score_repurposing_candidate(
+        drug=drug,
+        target_score=drug['target_association_score'],
+        safety_data=drug['safety_profile'],
+        literature_count=drug['supporting_papers']
+    )
+    drug['repurposing_score'] = score
+    scored_candidates.append(drug)
+
+# Sort by score
+ranked_candidates = sorted(
+    scored_candidates,
+    key=lambda x: x['repurposing_score'],
+    reverse=True
+)
+```
+
+## Alternative Strategies
+
+### Strategy A: Mechanism-Based Repurposing
+
+```python
+# Find drugs with similar mechanism of action
+known_drug = "metformin"
+
+# Get mechanism
+moa = tu.tools.drugbank_get_drug_desc_pharmacology_by_moa(
+    mechanism_of_action="[moa_term]"
+)
+
+# Get similar drugs
+similar = tu.tools.ChEMBL_search_similar_molecules(
+    query=known_drug,
+    similarity_threshold=70
+)
+```
+
+### Strategy B: Network-Based Repurposing
+
+```python
+# Use pathway analysis
+pathways = tu.tools.drugbank_get_pathways_reactions_by_drug_or_id(
+    drug_name_or_drugbank_id="[drug_name]"
+)
+
+# Find drugs affecting same pathways
+pathway_drugs = tu.tools.drugbank_get_drug_name_and_description_by_pathway_name(
+    pathway_name=pathways['data'][0]['pathway_name']
+)
+```
+
+### Strategy C: Phenotype-Based Repurposing
+
+```python
+# Search by indication/phenotype
+indication_drugs = tu.tools.drugbank_get_drug_name_and_description_by_indication(
+    indication="[related_indication]"
+)
+
+# Analyze adverse events as therapeutic effects
+# Example: minoxidil (hypertension) → hair growth
+adverse_as_therapeutic = tu.tools.FAERS_search_reports_by_drug_and_reaction(
+    drug_name="[drug_name]",
+    limit=1000
+)
+```
+
+## Key ToolUniverse Tools
+
+**Disease & Target Tools**:
+- `OpenTargets_get_disease_id_description_by_name` - Disease lookup
+- `OpenTargets_get_associated_targets_by_disease_efoId` - Disease targets
+- `UniProt_get_entry_by_accession` - Protein details
+
+**Drug Discovery Tools**:
+- `drugbank_get_drug_name_and_description_by_target_name` - Drugs by target
+- `drugbank_get_drug_name_and_description_by_indication` - Drugs by indication
+- `DGIdb_get_drug_gene_interactions` - Drug-gene interactions
+- `ChEMBL_search_drugs` - Drug search
+- `ChEMBL_get_drug_mechanisms` - Mechanism of action
+
+**Drug Information Tools**:
+- `drugbank_get_drug_basic_info_by_drug_name_or_id` - Basic drug info
+- `drugbank_get_indications_by_drug_name_or_drugbank_id` - Approved indications
+- `drugbank_get_pharmacology_by_drug_name_or_drugbank_id` - Pharmacology
+- `drugbank_get_targets_by_drug_name_or_drugbank_id` - Drug targets
+
+**Safety Assessment Tools**:
+- `FDA_get_warnings_and_cautions_by_drug_name` - FDA warnings
+- `FAERS_search_reports_by_drug_and_reaction` - Adverse events
+- `FAERS_count_death_related_by_drug` - Serious outcomes
+- `drugbank_get_drug_interactions_by_drug_name_or_id` - Interactions
+
+**Property Prediction Tools**:
+- `ADMETAI_predict_admet` - ADMET properties
+- `ADMETAI_predict_toxicity` - Toxicity prediction
+
+**Literature Tools**:
+- `PubMed_search_articles` - PubMed search
+- `EuropePMC_search_articles` - Europe PMC search
+- `ClinicalTrials_search` - Clinical trials
+
+## Output Format
+
+Present results as ranked candidates:
+
+```markdown
+## Drug Repurposing Analysis: [Disease Name]
+
+### Top 10 Repurposing Candidates
+
+#### 1. [Drug Name] (Score: 87/100)
+
+**Current Indications**: [list approved uses]
+**Proposed Indication**: [new disease/condition]
+**Repurposing Rationale**: Targets [gene/protein] with high association to disease
+
+**Evidence Summary**:
+- Target association score: 0.85
+- Approval status: FDA approved (safer profile)
+- Literature support: 23 papers, 4 clinical trials
+- Safety profile: No black box warnings
+
+**Mechanism**: [Brief mechanism description]
+
+**Next Steps**: 
+- Phase II trial feasibility assessment
+- Patient population identification
+- Dosing optimization study
+
+**Key Papers**:
+1. Smith et al. 2024 - Clinical efficacy in similar condition
+2. Jones et al. 2023 - Mechanism validation
+
+---
+
+#### 2. [Drug Name] (Score: 79/100)
+[Similar structure...]
+
+### Supporting Analysis
+
+**Target Network**: [visualization or description]
+**Pathway Overlap**: [affected pathways]
+**Safety Considerations**: [major concerns]
+**Development Timeline**: [estimated phases]
+```
+
+## Scoring Criteria
+
+**Target Association (0-40 points)**:
+- Strong genetic evidence: 40
+- Moderate association: 25
+- Pathway-level evidence: 15
+- Weak/predicted: 5
+
+**Safety Profile (0-30 points)**:
+- FDA approved: 20
+- Phase III: 15
+- Phase II: 10
+- Phase I: 5
+- No black box warning: +10
+- Known serious AE: -10
+
+**Literature Evidence (0-20 points)**:
+- Clinical trials: 5 points each (max 15)
+- Preclinical studies: 1 point each (max 10)
+- Case reports: 0.5 points each (max 5)
+
+**Drug Properties (0-10 points)**:
+- High bioavailability: 5
+- Good BBB penetration (if CNS): 5
+- Low toxicity predictions: 5
+
+## Best Practices
+
+1. **Start Broad**: Query multiple databases (DrugBank, ChEMBL, DGIdb)
+2. **Validate Targets**: Confirm target-disease associations in OpenTargets
+3. **Check Safety First**: Prioritize approved drugs with known safety profiles
+4. **Literature Mining**: Always search for existing clinical/preclinical evidence
+5. **Use Caching**: Enable `use_cache=True` for expensive predictions
+6. **Batch Operations**: Use `tu.run_batch()` for parallel queries
+7. **Consider Mechanism**: Evaluate biological plausibility
+8. **Patent Landscape**: Check if indication is already protected
+9. **Market Analysis**: Consider unmet medical need and commercial viability
+10. **Regulatory Path**: FDA approved drugs have faster repurposing path
+
+## Common Patterns
+
+### Pattern 1: Rapid Screening
+```python
+# Quick screening of 100+ drugs against disease targets
+targets = get_disease_targets(disease_id)[:10]
+all_drugs = []
+
+for target in targets:
+    drugs = tu.tools.DGIdb_get_drug_gene_interactions(
+        gene_name=target['gene_symbol']
+    )
+    all_drugs.extend(drugs)
+
+# Filter to FDA approved only
+approved_drugs = [d for d in all_drugs if d.get('approved')]
+```
+
+### Pattern 2: Deep Dive Single Drug
+```python
+# Comprehensive analysis of one drug candidate
+drug_name = "metformin"
+
+# Get everything
+info = tu.tools.drugbank_get_drug_basic_info_by_drug_name_or_id(drug_name_or_drugbank_id=drug_name)
+targets = tu.tools.drugbank_get_targets_by_drug_name_or_drugbank_id(drug_name_or_drugbank_id=drug_name)
+indications = tu.tools.drugbank_get_indications_by_drug_name_or_drugbank_id(drug_name_or_drugbank_id=drug_name)
+pharmacology = tu.tools.drugbank_get_pharmacology_by_drug_name_or_drugbank_id(drug_name_or_drugbank_id=drug_name)
+interactions = tu.tools.drugbank_get_drug_interactions_by_drug_name_or_id(drug_name_or_id=drug_name)
+warnings = tu.tools.FDA_get_warnings_and_cautions_by_drug_name(drug_name=drug_name)
+papers = tu.tools.PubMed_search_articles(query=f"{drug_name} AND [new_disease]", max_results=100)
+```
+
+### Pattern 3: Comparative Analysis
+```python
+# Compare multiple candidates side-by-side
+candidates = ["drug_a", "drug_b", "drug_c"]
+
+comparison = []
+for drug in candidates:
+    data = {
+        'name': drug,
+        'info': tu.tools.drugbank_get_drug_basic_info_by_drug_name_or_id(drug_name_or_drugbank_id=drug),
+        'safety': tu.tools.FDA_get_warnings_and_cautions_by_drug_name(drug_name=drug),
+        'evidence': tu.tools.PubMed_search_articles(query=drug, max_results=10)
+    }
+    comparison.append(data)
+```
+
+## Troubleshooting
+
+**"Disease not found"**: 
+- Try disease synonyms or EFO ID lookup
+- Use broader disease categories
+
+**"No drugs found for target"**:
+- Check target name/symbol (HUGO nomenclature)
+- Expand to pathway-level drugs
+- Consider similar targets (protein family)
+
+**"Insufficient literature evidence"**:
+- Search for drug class rather than specific drug
+- Check preclinical/animal studies
+- Look for mechanism papers
+
+**"Safety data unavailable"**:
+- Drug may not be FDA approved in US
+- Check EMA or other regulatory databases
+- Review clinical trial safety data
+
+## Example Use Cases
+
+**Use Case 1: Find repurposing candidates for rare disease**
+```python
+# Rare disease often lack approved drugs
+# Strategy: Find drugs targeting same pathways as related common diseases
+
+rare_disease = "Niemann-Pick disease"
+related_disease = "Alzheimer's disease"  # Similar pathology
+
+# Get pathways affected in related disease
+targets = tu.tools.OpenTargets_get_associated_targets_by_disease_efoId(
+    efoId=related_disease_id
+)
+
+# Find drugs for those targets
+# Evaluate for rare disease applicability
+```
+
+**Use Case 2: Repurpose based on adverse effects**
+```python
+# Adverse effect in one context = therapeutic in another
+# Example: Thalidomide (teratogenic) → cancer treatment
+
+drug = "drug_name"
+adverse_events = tu.tools.FAERS_search_reports_by_drug_and_reaction(
+    drug_name=drug,
+    limit=1000
+)
+
+# Analyze if adverse effects beneficial in other contexts
+# Example: weight loss AE → obesity treatment potential
+```
+
+**Use Case 3: Combination therapy discovery**
+```python
+# Find drugs that complement existing therapy
+primary_drug = "existing_therapy"
+disease = "disease_name"
+
+# Get targets not covered by primary drug
+disease_targets = tu.tools.OpenTargets_get_associated_targets_by_disease_efoId(
+    efoId=disease_id
+)
+
+primary_targets = tu.tools.drugbank_get_targets_by_drug_name_or_drugbank_id(
+    drug_name_or_drugbank_id=primary_drug
+)
+
+# Find drugs for uncovered targets
+uncovered_targets = [t for t in disease_targets if t not in primary_targets]
+```
+
+## Advanced Techniques
+
+### Technique 1: Polypharmacology-Based Repurposing
+```python
+# Find drugs with multi-target activity matching disease network
+
+# Get disease network
+targets = tu.tools.OpenTargets_get_associated_targets_by_disease_efoId(
+    efoId=disease_id,
+    limit=50
+)
+
+# For each drug, count how many disease targets it hits
+for drug in candidate_drugs:
+    drug_targets = tu.tools.drugbank_get_targets_by_drug_name_or_drugbank_id(
+        drug_name_or_drugbank_id=drug
+    )
+    
+    overlap = len(set(drug_targets) & set(disease_targets))
+    if overlap >= 3:  # Multi-target match
+        print(f"{drug}: hits {overlap} disease targets")
+```
+
+### Technique 2: Structure-Based Repurposing
+```python
+# Find structurally similar approved drugs
+
+known_active = "known_active_compound"
+
+# Get structure
+cid = tu.tools.PubChem_get_CID_by_compound_name(
+    compound_name=known_active
+)
+
+# Find similar
+similar = tu.tools.PubChem_search_compounds_by_similarity(
+    cid=cid['data']['cid'],
+    threshold=85
+)
+
+# Check which are approved drugs
+for compound in similar['data']:
+    drug_info = tu.tools.PubChem_get_drug_label_info_by_CID(
+        cid=compound['cid']
+    )
+```
+
+### Technique 3: AI-Powered Candidate Selection
+```python
+# Use ML predictions to filter candidates
+
+candidates_with_smiles = get_candidates_with_structures()
+
+# Predict ADMET for all
+admet_results = []
+for drug in candidates_with_smiles:
+    admet = tu.tools.ADMETAI_predict_admet(
+        smiles=drug['smiles'],
+        use_cache=True
+    )
+    admet_results.append({
+        'drug': drug['name'],
+        'admet': admet,
+        'pass': evaluate_admet_criteria(admet)
+    })
+
+# Keep only drugs passing ADMET criteria
+viable_candidates = [r for r in admet_results if r['pass']]
+```
+
+## Resources
+
+For comprehensive disease analysis, see [disease-intelligence-gatherer skill](../disease-intelligence-gatherer/SKILL.md).
+
+For compound property analysis, see [chemical-compound-retrieval skill](../chemical-compound-retrieval/SKILL.md).
+
+For detailed ToolUniverse SDK usage, see [tooluniverse-sdk skill](../tooluniverse-sdk/SKILL.md).