Towards computational prediction of microRNA function and activity |
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Authors: | Igor Ulitsky Louise C Laurent Ron Shamir |
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Institution: | 1.Blavatnik School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel, 2.Center for Regenerative Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037 and 3.Department of Reproductive Medicine, University of California, San Diego, 200 West Arbor Drive, San Diego, California 92103, USA |
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Abstract: | While it has been established that microRNAs (miRNAs) play key roles throughout development and are dysregulated in many human pathologies, the specific processes and pathways regulated by individual miRNAs are mostly unknown. Here, we use computational target predictions in order to automatically infer the processes affected by human miRNAs. Our approach improves upon standard statistical tools by addressing specific characteristics of miRNA regulation. Our analysis is based on a novel compendium of experimentally verified miRNA-pathway and miRNA-process associations that we constructed, which can be a useful resource by itself. Our method also predicts novel miRNA-regulated pathways, refines the annotation of miRNAs for which only crude functions are known, and assigns differential functions to miRNAs with closely related sequences. Applying our approach to groups of co-expressed genes allows us to identify miRNAs and genomic miRNA clusters with functional importance in specific stages of early human development. A full list of the predicted mRNA functions is available at http://acgt.cs.tau.ac.il/fame/. |
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