MicroRNAs (
miRNAs) are
small non-coding RNA molecules that regulate gene expression at a post-transcriptional level. An
miRNA may target many
messenger RNA (
mRNA) transcripts, and each transcript may be targeted by multiple
miRNAs. Our understanding of
miRNA regulation is evolving to consider modules of
miRNAs that regulate groups of functionally related mRNAs. Here we expand the model of
miRNA functional modules and use it to guide the integration of
miRNA and
mRNA expression and target prediction data. We present evidence of cooperativity between
miRNA classes within this integrated
miRNA-
mRNA association matrix. We then apply bicluster analysis to uncover
miRNA functional modules within this integrated data set and develop a novel application to visualize and query these results. We show that this wholly unsupervised approach can discover a network of
miRNA-
mRNA modules that are enriched for both biological processes and
miRNA classes. We apply this method to investigate the interplay of
miRNAs and mRNAs in integrated data sets derived from
neuroblastoma and human immune cells. This study is the first to apply the technique of biclustering to model functional modules within an integrated
miRNA-
mRNA association matrix. Results provide evidence of an extensive modular
miRNA functional network and enable characterization of
miRNA function and dysregulation in disease.