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Nucleic Acids Research Advance Access published online on January 16, 2009
Nucleic Acids Research, doi:10.1093/nar/gkn1064
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© 2009 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Computational Biology

Allegro: Analyzing expression and sequence in concert to discover regulatory programs

Yonit Halperin, Chaim Linhart, Igor Ulitsky and Ron Shamir*

School of Computer Science, Tel Aviv University, Tel Aviv 69978, Israel

*To whom correspondence should be addressed. Tel: +972 3 640 5383; Fax: +972 3 640 5384; Email: rshamir{at}post.tau.ac.il

Received November 10, 2008. Revised December 16, 2008. Accepted December 16, 2008.

A major goal of system biology is the characterization of transcription factors and microRNAs (miRNAs) and the transcriptional programs they regulate. We present Allegro, a method for de-novo discovery of cis-regulatory transcriptional programs through joint analysis of genome-wide expression data and promoter or 3' UTR sequences. The algorithm uses a novel log-likelihood-based, non-parametric model to describe the expression pattern shared by a group of co-regulated genes. We show that Allegro is more accurate and sensitive than existing techniques, and can simultaneously analyze multiple expression datasets with more than 100 conditions. We apply Allegro on datasets from several species and report on the transcriptional modules it uncovers. Our analysis reveals a novel motif over-represented in the promoters of genes highly expressed in murine oocytes, and several new motifs related to fly development. Finally, using stem-cell expression profiles, we identify three miRNA families with pivotal roles in human embryogenesis.

The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.


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