Centrality analysis in a drug network and its application to drug repositioning

•A novel application of centrality in a drug network is presented.•A centrality-guided approach for predicting drug repositioning candidates is proposed.•Topological advantages associated with central network positions of drugs may be translated into potential clinical benefits.•Significance of network centrality measures in drug development is discussed. Centrality measures play a vital role in network analysis by which important nodes within a network are identified from structural perspectives. In this study, we applied three fundamental centrality measures (degree, closeness, and betweenness) to analyze a drug network where drugs are connected based on their side-effect similarities. The results suggest that centralities of drugs in the network may have a significant implication in drug repositioning – a process of discovering new therapeutic uses of existing drugs. Given a particular disease, the drugs that have been approved for treating it were ranked by their centralities. It is shown that the top central ones among them are more likely to repurpose their neighboring drugs as new treatment options for the disease, as compared to their random and peripheral counterparts. Our predictions have proved to be in line with clinical interests indicated by the existing clinical studies in ClinicalTrials.gov database. The present work offers novel insights into complementing drug repositioning efforts while portraying the significance of network centrality measures in guiding systematic analysis for a successful network application.