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Evaluating tools for transcription factor binding site prediction

Martin, ACR; Jayaram, N; Usvyat, D; (2016) Evaluating tools for transcription factor binding site prediction. BMC Bioinformatics , 2016 , Article 1298. 10.1186/s12859-016-1298-9. Green open access

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Abstract

Background: Binding of transcription factors to transcription factor binding sites (TFBSs) is key to the mediation of transcriptional regulation. Information on experimentally validated functional TFBSs is limited and consequently there is a need for accurate prediction of TFBSs for gene annotation and in applications such as evaluating the effects of single nucleotide variations in causing disease. TFBSs are generally recognized by scanning a position weight matrix (PWM) against DNA using one of a number of available computer programs. Thus we set out to evaluate the best tools that can be used locally (and are therefore suitable for large-scale analyses) for creating PWMs from high-throughput ChIP-Seq data and for scanning them against DNA. Results: We evaluated a set of de novo motif discovery tools that could be downloaded and installed locally using ENCODE-ChIP-Seq data and showed that rGADEM was the best performing tool. TFBS prediction tools used to scan PWMs against DNA fall into two classes — those that predict individual TFBSs and those that identify clusters. Our evaluation showed that FIMO and MCAST performed best respectively. Conclusions: Selection of the best-performing tools for generating PWMs from ChIP-Seq data and for scanning PWMs against DNA has the potential to improve prediction of precise transcription factor binding sites within regions identified by ChIP-Seq experiments for gene finding, understanding regulation and in evaluating the effects of single nucleotide variations in causing disease.

Type: Article
Title: Evaluating tools for transcription factor binding site prediction
Open access status: An open access version is available from UCL Discovery
DOI: 10.1186/s12859-016-1298-9
Publisher version: http://dx.doi.org/10.1186/s12859-016-1298-9
Language: English
Additional information: Copyright © The Author(s) 2016. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Keywords: PWMs, motif discovery, performance evaluation, motif scanning tools
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology
URI: https://discovery.ucl.ac.uk/id/eprint/1524263
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