title: Discovery and visualization of miRNA-mRNA functional modules within integrated data using bicluster analysis.
abstract: 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.
authors.affiliation: Department of Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, York House, York Street, Dublin 2, Ireland, National Children's Research Centre, Our Lady's Children's Hospital, Crumlin, Dublin 12, Ireland and Department of Oncogenomics, Academic Medical Center, University of Amsterdam, 1100 DE Amsterdam, The Netherlands.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Bryan
authors.forename: Marta
authors.initials: M
authors.lastname: Terrile
authors.forename: Isabella M
authors.initials: IM
authors.lastname: Bray
authors.forename: Raquel
authors.initials: R
authors.lastname: Domingo-Fernandéz
authors.forename: Karen M
authors.initials: KM
authors.lastname: Watters
authors.forename: Jan
authors.initials: J
authors.lastname: Koster
authors.forename: Rogier
authors.initials: R
authors.lastname: Versteeg
authors.forename: Raymond L
authors.initials: RL
authors.lastname: Stallings
mesh_terms: D016000:Cluster Analysis; D003196:Computer Graphics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007107:Immune System / Q000378:metabolism; D035683:MicroRNAs / Q000145:classification / Q000378:metabolism*; D008957:Models, Genetic; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D012984:Software
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger