Yu Liang, Ma Xiaoke, Zhang Long, Zhang Jing, Gao Lin
School of Computer Science and Technology, Xidian University, Xi'an, 710071, P. R. China.
Department of Sports, Xidian University, Xi'an, 710071, P. R. China.
Sci Rep. 2016 Sep 28;6:32530. doi: 10.1038/srep32530.
Drug repositioning is commonly done within the drug discovery process in order to adjust or expand the application line of an active molecule. Previous computational methods in this domain mainly focused on shared genes or correlations between genes to construct new drug-disease associations. We propose a method that can not only handle drugs or diseases with or without related genes but consider the network modularity. Our method firstly constructs a drug network and a disease network based on side effects and symptoms respectively. Because similar drugs imply similar diseases, we then cluster the two networks to identify drug and disease modules, and connect all possible drug-disease module pairs. Further, based on known drug-disease associations in CTD and using local connectivity of modules, we predict potential drug-disease associations. Our predictions are validated by testing their overlaps with drug indications reported in published literatures and CTD, and KEGG enrichment analysis are also made on their related genes. The experimental results demonstrate that our approach can complement the current computational approaches and its predictions can provide new clues for the candidate discovery of drug repositioning.
药物重定位通常在药物发现过程中进行,以调整或扩展活性分子的应用范围。该领域以前的计算方法主要集中在共享基因或基因之间的相关性上,以构建新的药物-疾病关联。我们提出了一种方法,该方法不仅可以处理有或没有相关基因的药物或疾病,还能考虑网络模块化。我们的方法首先分别基于副作用和症状构建药物网络和疾病网络。由于相似的药物意味着相似的疾病,然后我们对这两个网络进行聚类以识别药物和疾病模块,并连接所有可能的药物-疾病模块对。此外,基于CTD中已知的药物-疾病关联并利用模块的局部连通性,我们预测潜在的药物-疾病关联。通过测试我们的预测与已发表文献和CTD中报道的药物适应症的重叠情况来验证我们的预测,并且还对其相关基因进行KEGG富集分析。实验结果表明,我们的方法可以补充当前的计算方法,其预测可以为药物重定位的候选发现提供新的线索。