Dynamic remodeling of context-specific miRNAs regulation networks facilitate in silico cancer drug screening

Abstract

Background: Much effort has been expended in exploring the connections between transcriptome, disease and drug, based on the premise that drug induced perturbations in the transcriptome will affect the phenotype and finally help to cure a disease. MicroRNAs (miRNAs) play a key role in the regulation of the transcriptome and have been identified as a key mediator in human disease and drug response. However, even if miRNA expression can be precisely detected, the information regarding miRNAs action on a particular part of the transcriptome is still lacking. Here, we introduced a novel concept, the Context-specific MiRNA activity (CoMi activity), to reflect a miRNA's regulation effect on a context specific gene set, by calculating the statistical difference between the distributions of its target gene expression and non-target gene expression. In this study we investigate whether CoMi activity could provide a novel perspective on miRNA mechanisms of action in disease and drug response, and facilitate in silico drug screening.