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Bioinformatics Advance Access originally published online on July 15, 2009
Bioinformatics 2009 25(18):2318-2325; doi:10.1093/bioinformatics/btp434
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Motif discovery and motif finding from genome-mapped DNase footprint data

Ivan V. Kulakovskiy 1,2,*, Alexander V. Favorov 2,3 and Vsevolod J. Makeev 1,2

1Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilov Street 32, Moscow 119991, 2State Scientific Institute of Genetics and Selection of Industrial Microorganisms, GosNIIgenetika, 1st Dorozhny proezd, 1, Moscow 117545, Russia and 3The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21231, USA

*To whom correspondence should be addressed.


  Abstract

Motivation: Footprint data is an important source of information on transcription factor recognition motifs. However, a footprinting fragment can contain no sequences similar to known protein recognition sites. Inspection of genome fragments nearby can help to identify missing site positions.

Results: Genome fragments containing footprints were supplied to a pipeline that constructed a position weight matrix (PWM) for different motif lengths and selected the optimal PWM. Fragments were aligned with the SeSiMCMC sampler and a new heuristic algorithm, Bigfoot. Footprints with missing hits were found for ~50% of factors. Adding only 2 bp on both sides of a footprinting fragment recovered most hits. We automatically constructed motifs for 41 Drosophila factors. New motifs can recognize footprints with a greater sensitivity at the same false positive rate than existing models. Also we discuss possible overfitting of constructed motifs.

Availability: Software and the collection of regulatory motifs are freely available at http://line.imb.ac.ru/DMMPMM.

Contact: ivan.kulakovskiy{at}gmail.com

Supplementary information: http://line.imb.ac.ru/DMMPMM

Associate Editor: Alex Bateman

Received on March 19, 2009; revised on July 7, 2009; accepted on July 11, 2009

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