Genome-wide dissection of microRNA functions and cotargeting networks using gene-set signatures
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van Oudenaarden_Genome-wide.pdf
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Author(s)
Tsang, John S.
Ebert, Margaret S.
van Oudenaarden, Alexander
Date Issued
April 2010
Journal
Molecular Cell
Publisher
Elsevier
Citation
Tsang, John S., Margaret S. Ebert, and Alexander van Oudenaarden. “Genome-wide Dissection of MicroRNA Functions and Cotargeting Networks Using Gene Set Signatures.” Molecular Cell 38.1 (2010): 140–153.
Version
Author's final manuscript
Abstract
MicroRNAs are emerging as important regulators of diverse biological processes and pathologies in animals and plants. Though hundreds of human microRNAs are known, only a few have known functions. Here, we predict human microRNA functions by using a new method that systematically assesses the statistical enrichment of several microRNA-targeting signatures in annotated gene sets such as signaling networks and protein complexes. Some of our top predictions are supported by published experiments, yet many are entirely new or provide mechanistic insights to known phenotypes. Our results indicate that coordinated microRNA targeting of closely connected genes is prevalent across pathways. We use the same method to infer which microRNAs regulate similar targets and provide the first genome-wide evidence of pervasive cotargeting, in which a handful of “hub” microRNAs are involved in a majority of cotargeting relationships. Our method and analyses pave the way to systematic discovery of microRNA functions.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Physics
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-Noncommercial-Share Alike 3.0
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DOI of Published Version
https://doi.org/10.1016/j.molcel.2010.03.007
