Mirsynergy: detecting synergistic miRNA regulatory modules by overlapping neighbourhood expansion.

Abstract

Identification of microRNA regulatory modules (MiRMs) 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, an efficient deterministic overlapping clustering algorithm adapted from a recently developed framework. Mirsynergy operates in two stages: it first forms MiRMs based on co-occurring microRNA (miRNA) targets and then expands each MiRM by greedily including (excluding) mRNAs into (from) the MiRM to maximize the synergy score, which is a function of miRNA-mRNA and gene-gene interactions. Using expression data for ovarian, breast and thyroid cancer from The Cancer Genome Atlas, we compared Mirsynergy with internal controls and existing methods. Mirsynergy-MiRMs exhibit significantly higher functional enrichment and more coherent miRNA-mRNA expression anti-correlation. Based on Kaplan-Meier survival analysis, we proposed several prognostically promising MiRMs and envisioned their utility in cancer research. Mirsynergy is implemented/available as an R/Bioconductor package at www.cs.utoronto.ca/∼yueli/Mirsynergy.html.