SynDRep: a synergistic partner prediction tool based on knowledge graph for drug repurposing.

Abstract

Motivation: Drug 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 (ML) techniques. This partner drug is then repurposed as a single agent for this disease by exploring pathways between them in the KG.

Results: HolE was the best-performing embedding model (with 84.58% of true predictions for all relations), and random forest emerged as the best ML model with an area under the receiver operating characteristic curve (ROC-AUC) value of 0.796. Some of our selected candidates, such as miconazole and albendazole for Alzheimer's disease, have been validated through literature, while others lack either a clear pathway or literature evidence for their use for the disease of interest. Therefore, complementing SynDRep with more specialized KGs, and additional training data, would enhance its efficacy and offer cost-effective and timely solutions for patients.

Availability and implementation: SynDRep is available as an open-source Python package at https://github.com/SynDRep/SynDRep under the Apache 2.0 License.