PATHOME-Drug

PATHOME-Drug identifies signaling subpathways enriched for targets of known and approved drugs and evaluates drug-associated transcriptomes using network-aware tests on KEGG pathways to support drug repositioning and mechanistic interpretation.

Key Features:

• Subpathway-Based Analysis: Identifies subparts of signaling cascades associated with phenotypic changes to link specific pathway regions to therapeutic effects.
• Polypharmacology Consideration: Evaluates multiple targets of known and approved drugs within identified subpathways to enable multi-target drug assessment and repositioning.
• Network-Aware Statistical Testing: Applies network-aware statistical tests to expression datasets using KEGG pathways as the pathway framework.
• Performance and Validation: Demonstrated superior performance over WebGestalt and clusterProfiler in detecting signaling contexts and identifying drugs across real biological and simulated datasets.

Scientific Applications:

• Drug Repositioning: Prioritizes existing and approved drugs whose targets are enriched in disease-relevant subpathways to discover new indications.
• Mechanistic Interpretation and Personalized Medicine: Integrates drug-associated transcriptomes with subpathway analysis to explore multi-target therapeutic mechanisms and support personalized medicine approaches.

Methodology:

Identifies subpathways within KEGG signaling pathways; evaluates enrichment of multiple drug targets per subpathway; applies network-aware statistical tests to expression datasets; and integrates drug-associated transcriptomes with subpathway analysis.