A drug repurposing method based on inhibition effect on gene regulatory network

Abstract

Numerous computational drug repurposing methods have emerged as efficient alternatives to costly and time-consuming traditional drug discovery approaches. Some of these methods are based on the assumption that the candidate drug should have a reversal effect on disease-associated genes. However, such methods are not applicable in the case that there is limited overlap between disease-related genes and drug-perturbed genes. In this study, we proposed a novel Drug Repurposing method based on the Inhibition Effect on gene regulatory network (DRIE) to identify potential drugs for cancer treatment. DRIE integrated gene expression profile and gene regulatory network to calculate inhibition score by using the shortest path in the disease-specific network. The results on eleven datasets indicated the superior performance of DRIE when compared to other state-of-the-art methods. Case studies showed that our method effectively discovered novel drug-disease associations. Our findings demonstrated that the top-ranked drug candidates had been already validated by CTD database. Additionally, it clearly identified potential agents for three cancers (colorectal, breast, and lung cancer), which was beneficial when annotating drug-disease relationships in the CTD. This study proposed a novel framework for drug repurposing, which would be helpful for drug discovery and development.

Keywords

• Drug repurposing
• Inhibition effect
• Gene regulatory network
• Drug-disease association