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BMC Bioinformatics

, 10:339

First Online: 16 October 2009Received: 10 March 2009Accepted: 16 October 2009

Abstract

BackgroundIt is known that transcription factors frequently act together to regulate gene expression in eukaryotes. In this paper we describe a computational analysis of transcription factor site dependencies in human, mouse and rat genomes.

ResultsOur approach for quantifying tendencies of transcription factor binding sites to co-occur is based on a binding site scoring function which incorporates dependencies between positions, the use of information about the structural class of each transcription factor major-minor groove binder, and also considered the possible implications of varying GC content of the sequences. Significant tendencies dependencies have been detected by non-parametric statistical methodology permutation tests. Evaluation of obtained results has been performed in several ways: reports from literature many of the significant dependencies between transcription factors have previously been confirmed experimentally; dependencies between transcription factors are not biased due to similarities in their DNA-binding sites; the number of dependent transcription factors that belong to the same functional and structural class is significantly higher than would be expected by chance; supporting evidence from GO clustering of targeting genes. Based on dependencies between two transcription factor binding sites second-order dependencies, it is possible to construct higher-order dependencies networks. Moreover results about transcription factor binding sites dependencies can be used for prediction of groups of dependent transcription factors on a given promoter sequence. Our results, as well as a scanning tool for predicting groups of dependent transcription factors binding sites are available on the Internet.

ConclusionWe show that the computational analysis of transcription factor site dependencies is a valuable complement to experimental approaches for discovering transcription regulatory interactions and networks. Scanning promoter sequences with dependent groups of transcription factor binding sites improve the quality of transcription factor predictions.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2105-10-339 contains supplementary material, which is available to authorized users.

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Autor: Andrija Tomovic - Michael Stadler - Edward J Oakeley

Fuente: https://link.springer.com/







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