On the power of profiles for transcription factor binding site detection

Statistical Applications in Genetics and Molecular Biology
Sven RahmannMartin Vingron

Abstract

Transcription factor binding site (TFBS) detection plays an important role in computational biology, with applications in gene finding and gene regulation. The sites are often modeled by gapless profiles, also known as position-weight matrices. Past research has focused on the significance of profile scores (the ability to avoid false positives), but this alone is not enough: The profile must also possess the power to detect the true positive signals. Several completed genomes are now available, and the search for TFBSs is moving to a large scale; so discriminating signal from noise becomes even more challenging. Since TFBS profiles are usually estimated from only a few experimentally confirmed instances, careful regularization is an important issue. We present a novel method that is well suited for this situation. We further develop measures that help in judging profile quality, based on both sensitivity and selectivity of a profile. It is shown that these quality measures can be efficiently computed, and we propose statistically well-founded methods to choose score thresholds. Our findings are applied to the TRANSFAC database of transcription factor binding sites. The results are disturbing: If we insist on a significance lev...Continue Reading

Citations

Oct 5, 2007·Journal of Biosciences·Abha S BaisMartin Vingron
Aug 20, 2005·Proceedings of the National Academy of Sciences of the United States of America·Fan LuGrace Wahba
Mar 17, 2009·BMC Bioinformatics·Bartek WilczynskiJerzy Tiuryn
Jun 29, 2010·BMC Bioinformatics·Matias PiipariTim Jp Hubbard
Jan 23, 2004·BMC Bioinformatics·Benjamin Schuster-BöcklerSven Rahmann
Aug 26, 2006·BMC Bioinformatics·Michael BeckstetteStefan Kurtz
Jan 24, 2007·BMC Bioinformatics·Dustin E SchonesMichael Q Zhang
Jan 24, 2008·BMC Bioinformatics·Ho-Joon LeeMartin Vingron
Feb 23, 2005·BMC Genomics·Christoph DieterichMartin Vingron
Mar 29, 2008·PLoS Computational Biology·Thomas MankeMartin Vingron
Oct 11, 2008·PLoS Computational Biology·Jun YanChunxuan Shao
Sep 16, 2008·PloS One·Szymon M Kiełbasa, Martin Vingron
Jun 14, 2005·Current Opinion in Genetics & Development·Tanya Vavouri, Greg Elgar
Feb 6, 2016·BMC Systems Biology·Aleksander JankowskiJerzy Tiuryn
Jul 27, 2010·Bio Systems·K BozekH Herzel
Dec 17, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Xiangbin XingMatthias P A Ebert
Feb 4, 2010·Human Mutation·Thomas MankeMartin Vingron
Sep 15, 2006·Computational Biology and Chemistry·Maria StepanovaValerie C-L Lin
Sep 3, 2013·Cell·Aarti JagannathStuart N Peirson
Mar 17, 2009·PloS One·Katarzyna BozekHanspeter Herzel
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Oct 7, 2010·Nucleic Acids Research·Alejandra Medina-RiveraJacques van Helden
Sep 30, 2017·Bioinformatics·Wolfgang Kopp, Martin Vingron
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Oct 22, 2011·Genome Biology and Evolution·Tomasz ZemojtelMartin Vingron
Dec 7, 2010·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Qing Zhou
Jan 28, 2015·Journal of Bacteriology·David Zamorano-SánchezFitnat H Yildiz
May 1, 2015·BMC Bioinformatics·Michal DabrowskiBartek Wilczynski

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