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Bioinformatics Advance Access originally published online on February 22, 2005
Bioinformatics 2005 21(10):2240-2245; 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{at}oupjournals.org

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 1,2, A. V. Gerasimova 1, D. A. Ravcheev 2,3, A. A. Mironov 1,3 and V. J. Makeev 1,4

1State Scientific Centre ‘GosNIIGenetika’ Laboratory for Bioinformatics 1st Dorozhny pr. 1, Moscow, 117545, Russia
2Institute of Information Transmission Problems, Russian Academy of Sciences Bolshoi Karetny per. 19, Moscow 127994, Russia
3Department of Bioengineering and Bioinformatics, Moscow State University Laboratory Building B, Vorobiovy Gory 1-73, Moscow 119992, Russia
4Engelhardt Institute of Molecular Biology, Russian Academy of Sciences Vavilova 32, Moscow 119991, Russia

*To whom correspondence should be addressed.

Motivation: Transcription regulatory protein factors often bind DNA as homo-dimers 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 owing to their high divergence. The motif structure included explicitly 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 are available at http://bioinform.genetika.ru/SeSiMCMC

Contact: favorov{at}sensi.org

Supplementary information: Supplementary material available at http://bioinform.genetika.ru/SeSiMCMC


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