Discovery and Visualization of MiRNA-mRNA Functional Modules Within Integrated Data Using Bicluster Analysis

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2013 Dec 21

PMID 24357407

Citations 19

Authors

Kenneth Bryan

Marta Terrile

Isabella M Bray

Raquel Domingo-Fernandez

Karen M Watters

Jan Koster

Rogier Versteeg

Raymond L Stallings

Affiliations

Soon will be listed here.

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.

Citing Articles

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Network-based cancer genomic data integration for pattern discovery.

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A holistic miRNA-mRNA module discovery.

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