文献类型：期刊文献

英文题名：Pathway-Based Drug Repurposing with DPNetinfer: A Method to Predict Drug-Pathway Associations via Network-Based Approaches

作者：Wang, Jiye[1];Wu, Zengrui[1];Peng, Yayuan[1];Li, Weihua[1];Liu, Guixia[1];Tang, Yun[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China

年份：2021

卷号：61

期号：5

起止页码：2475

外文期刊名：JOURNAL OF CHEMICAL INFORMATION AND MODELING

收录：;EI(收录号：20212210418448);WOS:【SCI-EXPANDED(收录号:WOS:000656118800033)】；

基金：This work was supported by the National Key Research and Development Program of China (grants 2016YFA0502304 and 2019YFA0904800), the National Natural Science Foundation of China (grants 81673356 and 81872800), the China Postdoctoral Science Foundation (grant 2019M661413), and Shanghai Sailing Program (grant 19YF1412700).

语种：英文

外文关键词：Computational methods - Diseases

摘要：Identification of drug-pathway associations plays an important role in pathway-based drug repurposing. However, it is time-consuming and costly to uncover new drug-pathway associations experimentally. The drug-induced transcriptomics data provide a global view of cellular pathways and tell how these pathways change under different treatments. These data enable computational approaches for large-scale prediction of drug-pathway associations. Here we introduced DPNetinfer, a novel computational method to predict potential drug-pathway associations based on substructure-drug-pathway networks via network-based approaches. The results demonstrated that DPNetinfer performed well in a pan-cancer network with an AUC (area under curve) = 0.9358. Meanwhile, DPNetinfer was shown to have a good capability of generalization on two external validation sets (AUC = 0.8519 and 0.7494, respectively). As a case study, DPNetinfer was used in pathway-based drug repurposing for cancer therapy. Unexpected anticancer activities of some nononcology drugs were then identified on the PI3K-Akt pathway. Considering tumor heterogeneity, seven primary site-based models were constructed by DPNetinfer in different drug-pathway networks. In a word, DPNetinfer provides a powerful tool for large-scale prediction of drugpathway associations in pathway-based drug repurposing. A web tool for DPNetinfer is freely available at http://lmmd.ecust.edu.cn/netinfer/.