ConBind: motif-aware cross-species alignment for the identification of functional transcription factor binding sitesReport as inadecuate


ConBind: motif-aware cross-species alignment for the identification of functional transcription factor binding sites


ConBind: motif-aware cross-species alignment for the identification of functional transcription factor binding sites - Download this document for free, or read online. Document in PDF available to download.

Publication Date: 2015-12-31

Journal Title: Nucleic Acids Research

Publisher: Oxford University Press

Language: English

Type: Article

Metadata: Show full item record

Citation: Lelieveld, S. H., Schütte, J., Dijkstra, M. J. J., Bawono, P., Kinston, S. J., Göttgens, B., Heringa, J., & et al. (2015). ConBind: motif-aware cross-species alignment for the identification of functional transcription factor binding sites. Nucleic Acids Research https://doi.org/10.1093/nar/gkv1518

Description: This is the final version of the article. It was first available from Oxford University Press via http://dx.doi.org/10.1093/nar/gkv1518

Abstract: Eukaryotic gene expression is regulated by transcription factors (TFs) binding to promoter as well as distal enhancers. TFs recognize short, but specific binding sites (TFBSs) that are located within the promoter and enhancer regions. Functionally relevant TFBSs are often highly conserved during evolution leaving a strong phylogenetic signal. While multiple sequence alignment (MSA) is a potent tool to detect the phylogenetic signal, the current MSA implementations are optimized to align the maximum number of identical nucleotides. This approach might result in the omission of conserved motifs that contain interchangeable nucleotides such as the ETS motif (IUPAC code: GGAW). Here, we introduce ConBind, a novel method to enhance alignment of short motifs, even if their mutual sequence similarity is only partial. ConBind improves the identification of conserved TFBSs by improving the alignment accuracy of TFBS families within orthologous DNA sequences. Functional validation of the Gfi1b + 13 enhancer reveals that ConBind identifies additional functionally important ETS binding sites that were missed by all other tested alignment tools. In addition to the analysis of known regulatory regions, our web tool is useful for the analysis of TFBSs on so far unknown DNA regions identified through ChIP-sequencing.

Sponsorship: N.B. wishes to acknowledge Beth Massa, Michael Klein, Eduard Beck (Microsoft), Kenji Takeda (Microsoft Research), Alie Kuiper, Sander van Dijk (SURFmarket) and Caroline Keulen (VU University Amsterdam) for their assistance with onboarding ConBind web services on Microsoft Azure.

Identifiers:

External DOI: https://doi.org/10.1093/nar/gkv1518

This record's URL: https://www.repository.cam.ac.uk/handle/1810/253170



Rights: Attribution 2.0 UK: England & Wales

Licence URL: http://creativecommons.org/licenses/by/2.0/uk/





Author: Lelieveld, Stefan H.Schütte, JudithDijkstra, Maurits J. J.Bawono, PuntoKinston, Sarah J.Göttgens, BertholdHeringa, JaapBonzanni,

Source: https://www.repository.cam.ac.uk/handle/1810/253170



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