Computational Drug Repositioning by Ranking and Integrating Multiple Data Sources

Abstract

Drug repositioning helps identify new indications for marketed drugs and clinical candidates. In this study, we proposed an integrative computational framework to predict novel drug indications for both approved drugs and clinical molecules by integrating chemical, biological and phenotypic data sources. We defined different similarity measures for each of these data sources and utilized a weighted k-nearest neighbor algorithm to transfer similarities of nearest neighbors to prediction scores for a given compound. A large margin method was used to combine individual metrics from multiple sources into a global metric. A large-scale study was conducted to repurpose 1007 drugs against 719 diseases. Experimental results showed that the proposed algorithm outperformed similar previously developed computational drug repositioning approaches. Moreover, the new algorithm also ranked drug information sources based on their contributions to the prediction, thus paving the way for prioritizing multiple data sources and building more reliable drug repositioning models.