PATHOME-Drug: a subpathway-based polypharmacology drug-repositioning method

Area of Science:

• Computational biology
• Pharmacology
• Bioinformatics

Background:

• Drug repositioning offers new therapeutic options for diseases lacking treatments.
• Current computational methods for drug repositioning have limitations in identifying specific signaling pathways and polypharmacology.

Purpose of the Study:

• To develop a subpathway-based polypharmacology drug repositioning method.
• To address limitations in existing drug repositioning tools by considering signaling context and multiple drug targets.

Main Methods:

• Developed PATHOME-Drug, a novel method utilizing drug-associated transcriptomes.
• Identified signaling subpathways related to phenotype changes.
• Enriched multiple drug targets within identified subpathways for drug repositioning.

Main Results:

• PATHOME-Drug demonstrated superior performance in detecting signaling context and specific drugs compared to WebGestalt and clusterProfiler.
• The method showed effectiveness on both real biological and simulated datasets.
• Successfully identified potential drug candidates by considering polypharmacology within specific subpathways.

Conclusions:

• PATHOME-Drug offers an effective approach for drug repositioning by integrating subpathway analysis and polypharmacology.
• The tool can aid in addressing the shortage of targeted therapy agents.
• Provides a valuable resource for discovering novel drug indications.