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Bioinformatics Advance Access published online on January 8, 2009
Bioinformatics, doi:10.1093/bioinformatics/btp018
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© The Author (2009). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Human microRNAs co-silence in well-separated groups and have different predicted essentialities

Gábor Boross 1,2, Katalin Orosz 1,2 and Illés J. Farkas 2,*

1Department of Biological Physics, Eötvös Loránd University,
2Statistical and Biological Physics Research Group and CellCom RET at the Hung. Acad. of Sci.,Pázmány P. stny. 1A, H-1117 Budapest, Hungary

*To whom correspondence should be addressed. Dr. Illés Farkas, E-mail: fij{at}angel.elte.hu, illes.farkas{at}gmail.com


  Abstract

Motivation: Short regulating RNAs guide many cellular processes. Compared to transcription factor proteins they appear to provide more specialised control and their deletions are less frequently lethal.

Results: We find large differences between computationally predicted lists of human microRNA-target pairs. Instead of integrating these lists we use the two most accurate of them. Next, we construct the co-regulation network of human microRNAs (miRNAs) as nodes by computing the correlation (link weight) between the gene silencing scores of individual miRNAs. In this network we locate groups of tightly co-regulating nodes (modules). Despite explicitly allowing overlaps the co-regulation modules of miRNAs are well separated. We use the modules and miRNA co-expression data to define and compute miRNA essentiality. Instead of focusing on particular biological functions we identify a miRNA as essential, if it has a low co-expression with the miRNAs in its module. This may be thought of as having many workers performing the same tasks together in one place (non-essential miRNAs) as opposed to a single worker performing those tasks alone (essential miRNA).

Conclusions: On the system level we quantitatively confirm previous findings about the specialised control provided by miRNAs. for knock-out tests we list the groups of our predicted most and least essential miRNAs. In addition, we provide possible explanations for (i) the low number of individually essential miRNAs in C. elegans (Miska et al., 2007) and (ii) the high number of ubiquitous miRNAs influencing cell and tissue-specific miRNA expression patterns (Landgraf et al., 2007) in mouse and human.

Contact: fij@elte.hu

Associate Editor: Dr. Jonathan Wren

Received on October 27, 2008; revised on December 14, 2008; accepted on January 6, 2009

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