Abstract

Transcription factors are proteins that bind to motifs on the DNA and thus affect gene expression regulation. The qualitative description of the corresponding processes is therefore important for a better understanding of essential biological mechanisms. However, wet lab experiments targeted at the discovery of the regulatory interplay between transcription factors and binding sites are expensive. We propose a new, purely computational method for finding putative associations between transcription factors and motifs. This method is based on a linear model that combines sequence information with expression data. We present various methods for model parameter estimation and show, via experiments on simulated data, that these methods are reliable. Finally, we examine the performance of this model on biological data and conclude that it can indeed be used to discover meaningful associations. The developed software is available as a web tool and Scilab source code at http://biit.cs.ut.ee/gmat/.

Highlights

  • Regulation of gene expression is one of the most important areas of contemporary biological research

  • A certain small set of Transcription factors (TFs) and motifs consistently occupied the top-scoring positions. This is rather similar to the situation in the GeneClass paper, where the exact ranking varied depending on the scoring algorithm, yet several TFs were consistently present in the top

  • We studied the applicability of the model to biological data

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Summary

Introduction

Regulation of gene expression is one of the most important areas of contemporary biological research. Of all the known mechanisms behind gene regulation, perhaps the most important one is the regulation of transcription by transcription factors [1,2]. Transcription factors (TFs) are proteins, which bind to certain short sequences (motifs) in the regulatory regions (promoters, enhancers, silencers) of genes. This can induce or suppress the transcription of these genes into mRNA and affect their expression as proteins. Discovery of regulatory relations between the transcription factors and the genes that they regulate forms a major challenge

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