Literature-based discovery of new candidates for drug repurposing

Abstract

Drug development is an expensive and time-consuming process; these could be reduced if the existing resources could be used to identify candidates for drug repurposing. This study sought to do this by text mining a large-scale literature repository to curate repurposed drug lists for different cancers. We devised a pattern-based relationship extraction method to extract disease-gene and gene-drug direct relationships from the literature. These direct relationships are used to infer indirect relationships using the ABC model. A gene-shared ranking method based on drug target similarity was then proposed to prioritize the indirect relationships. Our method of assessing drug target similarity correlated to existing anatomical therapeutic chemical code-based methods with a Pearson correlation coefficient of 0.9311. The indirect relationships ranking method achieved a significant mean average precision score of top 100 most common diseases. We also confirmed the suitability of candidates identified for repurposing as anticancer drugs by conducting a manual review of the literature and the clinical trials. Eventually, for visualization and enrichment of huge amount of repurposed drug information, a chord diagram was demonstrated to rapidly identify two novel indications for further biological evaluations.

Keywords: ABC model; drug repurposing; drug target discovery; information extraction; natural language processing; text-mining.