tooluniverse-network-pharmacology

安装量: 121
排名: #7074

安装

npx skills add https://github.com/mims-harvard/tooluniverse --skill tooluniverse-network-pharmacology
Network Pharmacology Pipeline
Construct and analyze compound-target-disease (C-T-D) networks to identify drug repurposing opportunities, understand polypharmacology, and predict drug mechanisms using systems pharmacology approaches.
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.
When to Use This Skill
Apply when users:
Ask "Can [drug] be repurposed for [disease] based on network analysis?"
Want to understand multi-target (polypharmacology) effects of a compound
Need compound-target-disease network construction and analysis
Ask about network proximity between drug targets and disease genes
Want systems pharmacology analysis of a drug or target
Ask about drug repurposing candidates ranked by network metrics
Need mechanism prediction for a drug in a new indication
Want to identify hub genes in disease networks as therapeutic targets
Ask about disease module coverage by a compound's targets
NOT for
(use other skills instead):
Simple drug repurposing without network analysis -> Use
tooluniverse-drug-repurposing
Single target validation -> Use
tooluniverse-drug-target-validation
Adverse event detection only -> Use
tooluniverse-adverse-event-detection
General disease research -> Use
tooluniverse-disease-research
GWAS interpretation -> Use
tooluniverse-gwas-snp-interpretation
Input Parameters
Parameter
Required
Description
Example
entity
Yes
Compound name/ID, target gene symbol/ID, or disease name/ID
metformin
,
EGFR
,
Alzheimer disease
entity_type
No
Type hint:
compound
,
target
, or
disease
(auto-detected if omitted)
compound
analysis_mode
No
compound-to-disease
,
disease-to-compound
,
target-centric
,
bidirectional
(default)
bidirectional
secondary_entity
No
Second entity for focused analysis (e.g., disease for compound input)
Alzheimer disease
Network Pharmacology Score (0-100)
Component
Max Points
Criteria for Max
Network Proximity
35
Z < -2, p < 0.01
Clinical Evidence
25
Approved for related indication
Target-Disease Association
20
Strong genetic evidence (GWAS, rare variants)
Safety Profile
10
FDA-approved, favorable safety
Mechanism Plausibility
10
Clear pathway mechanism with functional evidence
Priority Tiers
Score
Tier
Recommendation
80-100
Tier 1
High repurposing potential - proceed with experimental validation
60-79
Tier 2
Good potential - needs mechanistic validation
40-59
Tier 3
Moderate potential - high-risk/high-reward
0-39
Tier 4
Low potential - consider alternative approaches
Evidence Grading
Tier
Criteria
Examples
T1
Human clinical proof, regulatory evidence
FDA-approved, Phase III trial
T2
Functional experimental evidence
IC50 < 1 uM, CRISPR screen
T3
Association/computational evidence
GWAS hit, network proximity
T4
Prediction, annotation, text-mining
AlphaFold, literature co-mention
Full scoring details:
SCORING_REFERENCE.md
Key Principles
Report-first approach
- Create report file FIRST, then populate progressively
Entity disambiguation FIRST
- Resolve all identifiers before analysis
Bidirectional network
- Construct C-T-D network comprehensively from both directions
Network metrics
- Calculate proximity, centrality, module overlap quantitatively
Rank candidates
- Prioritize by composite Network Pharmacology Score
Mechanism prediction
- Explain HOW drug could work for disease via network paths
Clinical feasibility
- FDA-approved drugs ranked higher than preclinical
Safety context
- Flag known adverse events and off-target liabilities
Evidence grading
- Grade all evidence T1-T4
Negative results documented
- "No data" is data; empty sections are failures
Source references
- Every finding must cite the source tool/database
Completeness checklist
- Mandatory section at end showing analysis coverage
Workflow Overview
Phase 0: Entity Disambiguation and Report Setup
Create report file immediately
Resolve entity to all required IDs (ChEMBL, DrugBank, PubChem CID, Ensembl, MONDO/EFO)
Tools:
OpenTargets_get_drug_chembId_by_generic_name
,
drugbank_get_drug_basic_info_by_drug_name_or_id
,
PubChem_get_CID_by_compound_name
,
OpenTargets_get_target_id_description_by_name
,
OpenTargets_get_disease_id_description_by_name
Phase 1: Network Node Identification
Compound nodes
Drug targets, mechanism of action, current indications
Target nodes
Disease-associated genes, GWAS targets, druggability levels
Disease nodes
Related diseases, hierarchy, phenotypes
Tools:
OpenTargets_get_drug_mechanisms_of_action_by_chemblId
,
OpenTargets_get_associated_targets_by_drug_chemblId
,
drugbank_get_targets_by_drug_name_or_drugbank_id
,
DGIdb_get_drug_gene_interactions
,
CTD_get_chemical_gene_interactions
,
OpenTargets_get_associated_targets_by_disease_efoId
,
Pharos_get_target
Phase 2: Network Edge Construction
C-T edges
Bioactivity data (ChEMBL, DrugBank, BindingDB)
T-D edges
Genetic/functional associations (OpenTargets evidence, GWAS, CTD)
C-D edges
Clinical trials, CTD chemical-disease, literature co-mentions
T-T edges
PPI network (STRING, IntAct, OpenTargets interactions, HumanBase)
Tools:
ChEMBL_get_target_activities
,
OpenTargets_target_disease_evidence
,
GWAS_search_associations_by_gene
,
search_clinical_trials
,
CTD_get_chemical_diseases
,
STRING_get_interaction_partners
,
STRING_get_network
,
intact_search_interactions
,
humanbase_ppi_analysis
Phase 3: Network Analysis
Node degree, hub identification, betweenness centrality
Network modules (drug module vs disease module), module overlap
Shortest paths between drug targets and disease genes
Network proximity Z-score calculation
Functional enrichment (STRING, Enrichr, Reactome)
Tools:
STRING_functional_enrichment
,
STRING_ppi_enrichment
,
enrichr_gene_enrichment_analysis
,
ReactomeAnalysis_pathway_enrichment
Phase 4: Drug Repurposing Predictions
Identify drugs targeting disease genes (disease-to-compound mode)
Find diseases associated with drug targets (compound-to-disease mode)
Rank candidates by composite Network Pharmacology Score
Predict mechanisms via shared pathways and network paths
Tools:
OpenTargets_get_associated_drugs_by_target_ensemblID
,
drugbank_get_drug_name_and_description_by_target_name
,
drugbank_get_pathways_reactions_by_drug_or_id
Phase 5: Polypharmacology Analysis
Multi-target profiling (primary vs off-targets)
Disease module coverage calculation
Target family analysis and selectivity
Tools:
OpenTargets_get_target_classes_by_ensemblID
,
DGIdb_get_gene_druggability
,
OpenTargets_get_target_tractability_by_ensemblID
Phase 6: Safety and Toxicity Context
Adverse event profiling (FAERS disproportionality, OpenTargets AEs)
Target safety (gene constraints, expression, safety profiles)
FDA warnings, black box status
Tools:
FAERS_calculate_disproportionality
,
FAERS_filter_serious_events
,
FAERS_count_death_related_by_drug
,
FDA_get_warnings_and_cautions_by_drug_name
,
OpenTargets_get_drug_adverse_events_by_chemblId
,
OpenTargets_get_target_safety_profile_by_ensemblID
,
gnomad_get_gene_constraints
Phase 7: Validation Evidence
Clinical trials for drug-disease pair
Literature evidence (PubMed, EuropePMC)
ADMET predictions if SMILES available
Pharmacogenomics data
Tools:
search_clinical_trials
,
clinical_trials_get_details
,
PubMed_search_articles
,
EuropePMC_search_articles
,
ADMETAI_predict_toxicity
,
PharmGKB_get_drug_details
Phase 8: Report Generation
Compute Network Pharmacology Score from components
Generate report using template
Include completeness checklist
Full step-by-step code examples:
ANALYSIS_PROCEDURES.md
Report template:
REPORT_TEMPLATE.md
Critical Tool Parameter Notes
DrugBank tools
ALL require
query
,
case_sensitive
,
exact_match
,
limit
(4 params, ALL required)
FAERS analytics tools
ALL require
operation
parameter
FAERS count tools
Use
medicinalproduct
NOT
drug_name
OpenTargets tools
Return nested
{data: {entity: {field: ...}}}
structure
PubMed_search_articles
Returns plain list of dicts, NOT
{articles: [...]}
ReactomeAnalysis_pathway_enrichment
Takes space-separated
identifiers
string, NOT array
ensembl_lookup_gene
REQUIRES species='homo_sapiens' parameter Full tool parameter reference and response structures: TOOL_REFERENCE.md Fallback Strategies Phase Primary Tool Fallback 1 Fallback 2 Compound ID OpenTargets drug lookup ChEMBL search PubChem CID lookup Target ID OpenTargets target lookup ensembl_lookup_gene MyGene_query_genes Disease ID OpenTargets disease lookup ols_search_efo_terms CTD_get_chemical_diseases Drug targets OpenTargets drug mechanisms DrugBank targets DGIdb interactions Disease targets OpenTargets disease targets CTD gene-diseases GWAS associations PPI network STRING interactions OpenTargets interactions IntAct interactions Pathways ReactomeAnalysis enrichment enrichr enrichment STRING functional enrichment Clinical trials search_clinical_trials clinical_trials_search PubMed clinical Safety FAERS + FDA OpenTargets AEs DrugBank safety Literature PubMed search EuropePMC search OpenTargets publications Reference Files File Contents ANALYSIS_PROCEDURES.md Full code examples for each phase (Phases 0-8) REPORT_TEMPLATE.md Markdown template for final report output SCORING_REFERENCE.md Detailed scoring rubric and computation method TOOL_REFERENCE.md Tool signatures, response structures, troubleshooting USE_PATTERNS.md Common analysis patterns and edge case strategies QUICK_START.md Quick-start guide with minimal examples
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