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Zhou X, Dai E, Song Q, et al. In silico drug repositioning based on drug-miRNA associations. Brief Bioinform. 2020;21(2):498-510doi: 10.1093/bib/bbz012.
Zhou, X., Dai, E., Song, Q., Ma, X., Meng, Q., Jiang, Y., & Jiang, W. (2020). In silico drug repositioning based on drug-miRNA associations. Briefings in bioinformatics, 21(2), 498-510. https://doi.org/10.1093/bib/bbz012
Zhou, Xu, et al. "In silico drug repositioning based on drug-miRNA associations." Briefings in bioinformatics vol. 21,2 (2020): 498-510. doi: https://doi.org/10.1093/bib/bbz012
Zhou X, Dai E, Song Q, Ma X, Meng Q, Jiang Y, Jiang W. In silico drug repositioning based on drug-miRNA associations. Brief Bioinform. 2020 Mar 23;21(2):498-510. doi: 10.1093/bib/bbz012. PMID: 30753359.
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Brief Bioinform. 2020 Mar 23;21(2):498-510. doi: 10.1093/bib/bbz012.

In silico drug repositioning based on drug-miRNA associations.

Briefings in bioinformatics

Xu Zhou, Enyu Dai, Qian Song, Xueyan Ma, Qianqian Meng, Yongshuai Jiang, Wei Jiang

Affiliations

  1. College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, P. R. China.
  2. Department of Biomedical Engineering, College of Automation Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, P. R. China.

PMID: 30753359 DOI: 10.1093/bib/bbz012

Abstract

Drug repositioning has become a prevailing tactic as this strategy is efficient, economical and low risk for drug discovery. Meanwhile, recent studies have confirmed that small-molecule drugs can modulate the expression of disease-related miRNAs, which indicates that miRNAs are promising therapeutic targets for complex diseases. In this study, we put forward and verified the hypothesis that drugs with similar miRNA profiles may share similar therapeutic properties. Furthermore, a comprehensive drug-drug interaction network was constructed based on curated drug-miRNA associations. Through random network comparison, topological structure analysis and network module extraction, we found that the closely linked drugs in the network tend to treat the same diseases. Additionally, the curated drug-disease relationships (from the CTD) and random walk with restarts algorithm were utilized on the drug-drug interaction network to identify the potential drugs for a given disease. Both internal validation (leave-one-out cross-validation) and external validation (independent drug-disease data set from the ChEMBL) demonstrated the effectiveness of the proposed approach. Finally, by integrating drug-miRNA and miRNA-disease information, we also explain the modes of action of drugs in the view of miRNA regulation. In summary, our work could determine novel and credible drug indications and offer novel insights and valuable perspectives for drug repositioning.

© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Keywords: drug repositioning; drug-miRNA network; drug–drug network; microRNA; random walk

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