NMSDR: Drug repurposing approach based on transcriptome data and network module similarity.

Abstract

Computational drug repurposing aims to discover new treatment regimens by analyzing approved drugs on the market. This study proposes previously approved compounds that can change the expression profile of disease-causing proteins by developing a network theory-based drug repurposing approach. The novelty of the proposed approach is an exploration of module similarity between a disease-causing network and a compound-specific interaction network; thus, such an association leads to more realistic modeling of molecular cell responses at a system biology level. The overlap of the disease network and each compound-specific network is calculated based on a shortest-path similarity of networks by accounting for all protein pairs between networks. A higher similarity score indicates a significant potential of a compound. The approach was validated for breast and lung cancers. When all compounds are sorted by their normalized-similarity scores, 36 and 16 drugs are proposed as new candidates for breast and lung cancer treatment, respectively. A literature survey on candidate compounds revealed that some of our predictions have been clinically investigated in phase II/III trials for the treatment of two cancer types. As a summary, the proposed approach has provided promising initial results by modeling biochemical cell responses in a network-level data representation.