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Wellington : a novel method for the accurate identification of digital genomic footprints from DNase-seq data
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Piper, Jason, Elze, Markus C., Cauchy, Pierre, Cockerill, Peter N., Bonifer, Constanze and Ott, Sascha (2013) Wellington : a novel method for the accurate identification of digital genomic footprints from DNase-seq data. Nucleic Acids Research, Volume 41 (Number 21). Article number e201. doi:10.1093/nar/gkt850 ISSN 0305-1048.
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Official URL: http://dx.doi.org/10.1093/nar/gkt850
Abstract
The expression of eukaryotic genes is regulated by cis-regulatory elements such as promoters and enhancers, which bind sequence-specific DNA-binding proteins. One of the great challenges in the gene regulation field is to characterise these elements. This involves the identification of transcription factor (TF) binding sites within regulatory elements that are occupied in a defined regulatory context. Digestion with DNase and the subsequent analysis of regions protected from cleavage (DNase footprinting) has for many years been used to identify specific binding sites occupied by TFs at individual cis-elements with high resolution. This methodology has recently been adapted for high-throughput sequencing (DNase-seq). In this study, we describe an imbalance in the DNA strand-specific alignment information of DNase-seq data surrounding protein–DNA interactions that allows accurate prediction of occupied TF binding sites. Our study introduces a novel algorithm, Wellington, which considers the imbalance in this strand-specific information to efficiently identify DNA footprints. This algorithm significantly enhances specificity by reducing the proportion of false positives and requires significantly fewer predictions than previously reported methods to recapitulate an equal amount of ChIP-seq data. We also provide an open-source software package, pyDNase, which implements the Wellington algorithm to interface with DNase-seq data and expedite analyses.
Item Type: | Journal Article | ||||
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Subjects: | Q Science > QA Mathematics Q Science > QH Natural history > QH301 Biology Q Science > QH Natural history > QH426 Genetics |
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Divisions: | Faculty of Science, Engineering and Medicine > Science > Statistics Faculty of Science, Engineering and Medicine > Research Centres > Warwick Systems Biology Centre |
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Library of Congress Subject Headings (LCSH): | Algorithms, Genes, Genetic regulation, DNA | ||||
Journal or Publication Title: | Nucleic Acids Research | ||||
Publisher: | Oxford University Press | ||||
ISSN: | 0305-1048 | ||||
Official Date: | 25 September 2013 | ||||
Dates: |
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Volume: | Volume 41 | ||||
Number: | Number 21 | ||||
Page Range: | Article number e201 | ||||
DOI: | 10.1093/nar/gkt850 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Open Access (Creative Commons) | ||||
Date of first compliant deposit: | 26 December 2015 | ||||
Date of first compliant Open Access: | 26 December 2015 | ||||
Funder: | Engineering and Physical Sciences Research Council (EPSRC), University of Warwick Vice Chancellor Scholarship, Studienstiftung des Deutschen Volkes [German National Academic Foundation], Leukaemia & Lymphoma Research (LLR), Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC) | ||||
Grant number: | EP/P50578X/1 (EPSRC) ; BB/I001220/1 (BBSRC) |
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