SynDRep: A Knowledge Graph-Enhanced Tool based on Synergistic Partner Prediction for Drug Repurposing

Abstract

AbstractDrug repurposing is gaining interest due to its high cost-effectiveness, low risks, and improved patient outcomes. However, most drug repurposing methods depend on drug-disease-target semantic connections of a single drug rather than insights from drug combination data. In this study, we propose SynDRep, a novel drug repurposing tool based on enriching knowledge graphs (KG) with drug combination effects. It predicts the synergistic drug partner with a commonly prescribed drug for the target disease, leveraging graph embedding and machine learning techniques. This partner drug is then repurposed as a single agent for this disease by exploring pathways between them in KG. Some of our selected candidates, such as miconazole and albendazole for Alzheimer’s disease, have been validated, while others lack either a clear pathway or literature evidence for their use for the disease of interest. Therefore, complementing SynDRep with more specialized KG, and additional training data, would enhance its efficacy and offer cost-effective and timely solutions for patients.