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Bioinformatics Advance Access published online on February 22, 2005
Bioinformatics, doi:10.1093/bioinformatics/bti336
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© The Author (2005). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org
Received January 27, 2005
Accepted February 16, 2005

Article

A Gibbs sampler for identification of symmetrically structured, spaced DNA motifs with improved estimation of the signal length

A. V. Favorov 1*, M. S. Gelfand 2, A. V. Gerasimova 1, D. A. Ravcheev 3, A. A. Mironov 4, and V. J. Makeev 5

1 State Scientific Centre "GosNIIGenetika", 1st Dorozhny pr. 1, Moscow, 117545, Russia
2 State Scientific Centre "GosNIIGenetika", 1st Dorozhny pr. 1, Moscow, 117545, Russia; Institute of Information Transmission Problems, Russian Academy of Sciences, Bolshoi Karetny per. 19, Moscow, 127994, Russia
3 Institute of Information Transmission Problems, Russian Academy of Sciences, Bolshoi Karetny per. 19, Moscow, 127994, Russia; Dept. of Bioengineering and Bioinformatics, Moscow State University, Lab. Bldg B, Vorobiovy Gory 1-73, Moscow 119992, Russia
4 State Scientific Centre "GosNIIGenetika", 1st Dorozhny pr. 1, Moscow, 117545, Russia; Dept. of Bioengineering and Bioinformatics, Moscow State University, Lab. Bldg B, Vorobiovy Gory 1-73, Moscow 119992, Russia
5 State Scientific Centre "GosNIIGenetika", 1st Dorozhny pr. 1, Moscow, 117545, Russia; Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Vavilova 32, Moscow 119991, Russia

* To whom correspondence should be addressed.
A. V. Favorov, E-mail: favorov{at}sensi.org


  Abstract

Motivation: Transcription regulatory protein factors often bind DNA as homo- or hetero-dimers. Thus they recognize structured DNA motifs that are inverted or direct repeats or spaced motif pairs. However, these motifs are often difficult to identify due to their high divergency. The motif structure included explicitely into the motif recognition algorithm improves recognition efficiency for highly divergent motifs as well as estimation of motif geometric parameters.

Result: We present a modification of the Gibbs sampling motif extraction algorithm, SeSiMCMC (Sequence Similarities by Markov Chain Monte-Carlo), which finds structured motifs of these types, as well as non-structured motifs, in a set of unaligned DNA sequences. It employs improved estimators of motif and spacer lengths. The probability that a sequence does not contain any motif is accounted for in a rigorous Bayesian manner. We have applied the algorithm to a set of upstream regions of genes from two Escherichia coli regulons involved in respiration. We have demonstrated that accounting for a symmetric motif structure allows the algorithm to identify weak motifs more accurately. In the examples studied, ArcA binding sites were demonstrated to have the structure of a direct spaced repeat, whereas NarP binding sites exhibited the palindromic structure.

Availability: The WWW interface of the program, its FreeBSD (4.0) and Windows 32 console executables, and some additional documentation are available at http://bioinform.genetika.ru/SeSiMCMC.


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