Computational drug repositioning approaches are important, as they cost less compared to the traditional drug development processes. This study proposes a novel network-based drug repositioning approach, which computes similarities between disease-causing genes and drug-affected genes in a network topology to suggest candidate drugs with highest similarity scores. This new method aims to identify better treatment options by integrating systems biology approaches. It uses a protein-protein interaction network that is the main topology to compute a similarity score between candidate drugs and disease-causing genes. The disease-causing genes were mapped on this network structure. Transcriptome profiles of drug candidates were taken from the LINCS project and mapped individually on the network structure. The similarity of these two networks was calculated by different network neighborhood metrics, including Adamic-Adar, PageRank and neighborhood scoring. The proposed approach identifies the best candidates by choosing the drugs with significant similarity scores. The method was experimented on melanoma, colorectal, and prostate cancers. Several candidate drugs were predicted by applying AUC values of 0.6 or higher. Some of the predictions were approved by clinical phase trials or other in-vivo studies found in literature. The proposed drug repositioning approach would suggest better treatment options with integration of functional information between genes and transcriptome level effects of drug perturbations and diseases.
Keywords: Adamic-Adar; Colorectal cancer; Computational drug repositioning; Melanoma; Neighborhood scoring; PageRank; Prostate cancer.
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