BiModule: biclique modularity strategy for identifying transcription factor and microRNA co-regulatory modules

Systematic identification of gene regulatory modules can provide invaluable knowledge towards understanding aberrant transcriptional/post-transcriptional collaborative regulatory (co-regulatory) effects in cancer. Transcription factor (TF) and microRNA (miRNA) are known as two classes of prominent regulators that play crucial roles in gene regulation. Existing studies on gene regulatory modules identification mainly focused on the miRNA-mediated regulatory network, and few considered these two regulators in a co-occurring network. In this current study, we developed a computational method called BiModule for systematically identifying TF-miRNA co-regulatory modules. BiModule operates in two main stages: it first constructs a cancerspecific regulator-mRNA network and then identifies modules based on maximal bicliques by employing biclique modularity strategy, which is a novel flexible method for bipartite graph mining. We applied our model to a cervical cancer dataset. The results showed that the TF-miRNA co-regulatory modules identified by BiModule exhibit denser connections and stronger expression correlations than another existing related method. Moreover, the BiModule-modules exhibit high biological functional enrichment. In addition, based on Kaplan-Meier survival analysis, we found a number of modules with significant prognostic associations.