Cross-species comparison significantly improves genome-wide prediction of cis-regulatory modules in Drosophila

BMC Bioinformatics
Saurabh SinhaEric D Siggia

Abstract

The discovery of cis-regulatory modules in metazoan genomes is crucial for understanding the connection between genes and organism diversity. It is important to quantify how comparative genomics can improve computational detection of such modules. We run the Stubb software on the entire D. melanogaster genome, to obtain predictions of modules involved in segmentation of the embryo. Stubb uses a probabilistic model to score sequences for clustering of transcription factor binding sites, and can exploit multiple species data within the same probabilistic framework. The predictions are evaluated using publicly available gene expression data for thousands of genes, after careful manual annotation. We demonstrate that the use of a second genome (D. pseudoobscura) for cross-species comparison significantly improves the prediction accuracy of Stubb, and is a more sensitive approach than intersecting the results of separate runs over the two genomes. The entire list of predictions is made available online. Evolutionary conservation of modules serves as a filter to improve their detection in silico. The future availability of additional fruitfly genomes therefore carries the prospect of highly specific genome-wide predictions using Stubb.

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Citations

Oct 5, 2007·Journal of Biosciences·Rahul Siddharthan
Jun 19, 2012·Nature Reviews. Genetics·Ross C Hardison, James Taylor
Oct 27, 2006·Proceedings of the National Academy of Sciences of the United States of America·Saurabh SinhaGene E Robinson
Jun 6, 2009·Briefings in Functional Genomics & Proteomics·Leelavati Narlikar, Ivan Ovcharenko
Jun 6, 2009·Briefings in Bioinformatics·Peter Van Loo, Peter Marynen
Dec 8, 2005·Bioinformatics·Tilman SauerEdgar Wingender
Jun 28, 2005·Nucleic Acids Research·Stein AertsBart De Moor
Jul 18, 2006·Nucleic Acids Research·Saurabh SinhaEric Siggia
Dec 7, 2006·Nucleic Acids Research·Vincent FerrettiMathieu Blanchette
May 20, 2011·Nucleic Acids Research·Majid KazemianSaurabh Sinha
Nov 5, 2008·Genome Research·Steven G KuntzBarbara J Wold
Feb 22, 2007·Annual Review of Biophysics and Biomolecular Structure·Harmen J BussemakerLucas D Ward
Jan 24, 2007·BMC Bioinformatics·Dustin E SchonesMichael Q Zhang
Nov 1, 2008·Genome Biology·Debashis SahooSylvia K Plevritis
Nov 14, 2007·PLoS Computational Biology·Saurabh Sinha, Xin He
Sep 5, 2008·PLoS Computational Biology·Rahul Siddharthan
Dec 15, 2010·PLoS Computational Biology·Jing SuThomas A Down
Oct 15, 2011·PLoS Computational Biology·Armita Nourmohammad, Michael Lässig
Jan 10, 2009·PLoS Genetics·Jaebum KimSaurabh Sinha
Sep 5, 2009·PloS One·Garmay Leung, Michael B Eisen
Aug 16, 2012·Molecular Systems Biology·Zeba WunderlichAngela H DePace
Jul 4, 2018·Genes, Brain, and Behavior·Michael C SaulSaurabh Sinha
Sep 14, 2010·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Noboru J Sakabe, Marcelo A Nobrega

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Software Mentioned

Stubb
Ahab
BDGP
STUBBSS
PFR
Searcher
LAGAN
CONTIGMAP
STUBBMS

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