A drug repurposing method based on inhibition effect on gene regulatory network
Xianbin Li, Minzhen Liao, Bing Wang, Xiangzhen Zan, Yanhao Huo, Yue Liu, Zhenshen Bao, Peng Xu, Wenbin Liu · Computational and Structural Biotechnology Journal · 2023
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 D rug R epurposing method based on the I nhibition E ffect 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.