Mirsynergy: detect synergistic miRNA regulatory modules by overlapping neighbourhood expansion

MicroRNAs (miRNAs) are ∼22 nucleotide small noncoding RNA that base-pair with mRNA primarily at the 3′ untranslated region (UTR) to cause mRNA degradation or translational repression [1]. Aberrant miRNA expression is implicated in tumorigenesis [4]. Construction of microRNA regulatory modules (MiRM) will aid deciphering aberrant transcriptional regulatory network in cancer but is computationally challenging. Existing methods are stochastic or require a fixed number of regulatory modules. We propose Mirsynergy, a deterministic overlapping clustering algorithm adapted from a recently developed framework. Briefly, Mirsynergy operates in two stages that first forms MiRM based on co-occurring miRNAs and then expand the MiRM by greedily including (excluding) mRNA into (from) the MiRM to maximize the synergy score, which is a function of miRNA-mRNA and gene-gene interactions (manuscript in prep).