Assessing computational tools for the discovery of transcription factor binding sites

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Abstract

The prediction of regulatory elements is a problem where computational methods offer great hope. Over the past few years, numerous tools have become available for this task. The purpose of the current assessment is twofold: to provide some guidance to users regarding the accuracy of currently available tools in various settings, and to provide a benchmark of data sets for assessing future tools.

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Most cited references 14

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TRANSFAC: a database on transcription factors and their DNA binding sites.

E. Wingender, P Dietze, H Karas … (1996)

TRANSFAC is a database about eukaryotic transcription regulating DNA sequence elements and the transcription factors binding to and acting through them. This report summarizes the present status of this database and accompanying retrieval tools.

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Computational identification of cis-regulatory elements associated with groups of functionally related genes in Saccharomyces cerevisiae.

J D Hughes, P Estep, S Tavazoie … (2000)

AlignACE is a Gibbs sampling algorithm for identifying motifs that are over-represented in a set of DNA sequences. When used to search upstream of apparently coregulated genes, AlignACE finds motifs that often correspond to the DNA binding preferences of transcription factors. We previously used AlignACE to analyze whole genome mRNA expression data. Here, we present a more detailed study of its effectiveness as applied to a variety of groups of genes in the Saccharomyces cerevisiae genome. Published functional catalogs of genes and sets of genes grouped by common name provided 248 groups, resulting in 3311 motifs. In conjunction with this analysis, we present measures for gauging the tendency of a motif to target a given set of genes relative to all other genes in the genome and for gauging the degree to which a motif is preferentially located in a certain distance range upstream of translational start sites. We demonstrate improved methods for comparing and clustering sequence motifs. Many previously identified cis-regulatory elements were found. We also describe previously unidentified motifs, one of which has been verified by experiments in our laboratory. An extensive set of AlignACE runs on randomly selected sets of genes and on sets of genes whose upstream regions contain known transcription factor binding sites serve as controls. Copyright 2000 Academic Press.

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Extracting regulatory sites from the upstream region of yeast genes by computational analysis of oligonucleotide frequencies.

J van Helden, B André, J Collado-Vides (1998)

We present here a simple and fast method allowing the isolation of DNA binding sites for transcription factors from families of coregulated genes, with results illustrated in Saccharomyces cerevisiae. Although conceptually simple, the algorithm proved efficient for extracting, from most of the yeast regulatory families analyzed, the upstream regulatory sequences which had been previously found by experimental analysis. Furthermore, putative new regulatory sites are predicted within upstream regions of several regulons. The method is based on the detection of over-represented oligonucleotides. A specificity of this approach is to define the statistical significance of a site based on tables of oligonucleotide frequencies observed in all non-coding sequences from the yeast genome. In contrast with heuristic methods, this oligonucleotide analysis is rigorous and exhaustive. Its range of detection is however limited to relatively simple patterns: short motifs with a highly conserved core. These features seem to be shared by a good number of regulatory sites in yeast. This, and similar methods, should be increasingly required to identify unknown regulatory elements within the numerous new coregulated families resulting from measurements of gene expression levels at the genomic scale. All tools described here are available on the web at the site http://copan.cifn.unam.mx/Computational_Biology/ yeast-tools Copyright 1998 Academic Press