Chromatin accessibility data sets show bias due to sequence specificity of the DNase I enzyme.

<h4>Background</h4>DNase I is an enzyme which cuts duplex DNA at a rate that depends strongly upon its chromatin environment. In combination with high-throughput sequencing (HTS) technology, it can be used to infer genome-wide landscapes of open chromatin regions. Using this technology,...

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Autores principales:	Hashem Koohy, Thomas A Down, Tim J Hubbard
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/07f3562fbdd9490287ef1b6281a41eec
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spelling	oai:doaj.org-article:07f3562fbdd9490287ef1b6281a41eec2021-11-18T09:02:41ZChromatin accessibility data sets show bias due to sequence specificity of the DNase I enzyme.1932-620310.1371/journal.pone.0069853https://doaj.org/article/07f3562fbdd9490287ef1b6281a41eec2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23922824/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>DNase I is an enzyme which cuts duplex DNA at a rate that depends strongly upon its chromatin environment. In combination with high-throughput sequencing (HTS) technology, it can be used to infer genome-wide landscapes of open chromatin regions. Using this technology, systematic identification of hundreds of thousands of DNase I hypersensitive sites (DHS) per cell type has been possible, and this in turn has helped to precisely delineate genomic regulatory compartments. However, to date there has been relatively little investigation into possible biases affecting this data.<h4>Results</h4>We report a significant degree of sequence preference spanning sites cut by DNase I in a number of published data sets. The two major protocols in current use each show a different pattern, but for a given protocol the pattern of sequence specificity seems to be quite consistent. The patterns are substantially different from biases seen in other types of HTS data sets, and in some cases the most constrained position lies outside the sequenced fragment, implying that this constraint must relate to the digestion process rather than events occurring during library preparation or sequencing.<h4>Conclusions</h4>DNase I is a sequence-specific enzyme, with a specificity that may depend on experimental conditions. This sequence specificity is not taken into account by existing pipelines for identifying open chromatin regions. Care must be taken when interpreting DNase I results, especially when looking at the precise locations of the reads. Future studies may be able to improve the sensitivity and precision of chromatin state measurement by compensating for sequence bias.Hashem KoohyThomas A DownTim J HubbardPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e69853 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hashem Koohy Thomas A Down Tim J Hubbard Chromatin accessibility data sets show bias due to sequence specificity of the DNase I enzyme.
description	<h4>Background</h4>DNase I is an enzyme which cuts duplex DNA at a rate that depends strongly upon its chromatin environment. In combination with high-throughput sequencing (HTS) technology, it can be used to infer genome-wide landscapes of open chromatin regions. Using this technology, systematic identification of hundreds of thousands of DNase I hypersensitive sites (DHS) per cell type has been possible, and this in turn has helped to precisely delineate genomic regulatory compartments. However, to date there has been relatively little investigation into possible biases affecting this data.<h4>Results</h4>We report a significant degree of sequence preference spanning sites cut by DNase I in a number of published data sets. The two major protocols in current use each show a different pattern, but for a given protocol the pattern of sequence specificity seems to be quite consistent. The patterns are substantially different from biases seen in other types of HTS data sets, and in some cases the most constrained position lies outside the sequenced fragment, implying that this constraint must relate to the digestion process rather than events occurring during library preparation or sequencing.<h4>Conclusions</h4>DNase I is a sequence-specific enzyme, with a specificity that may depend on experimental conditions. This sequence specificity is not taken into account by existing pipelines for identifying open chromatin regions. Care must be taken when interpreting DNase I results, especially when looking at the precise locations of the reads. Future studies may be able to improve the sensitivity and precision of chromatin state measurement by compensating for sequence bias.
format	article
author	Hashem Koohy Thomas A Down Tim J Hubbard
author_facet	Hashem Koohy Thomas A Down Tim J Hubbard
author_sort	Hashem Koohy
title	Chromatin accessibility data sets show bias due to sequence specificity of the DNase I enzyme.
title_short	Chromatin accessibility data sets show bias due to sequence specificity of the DNase I enzyme.
title_full	Chromatin accessibility data sets show bias due to sequence specificity of the DNase I enzyme.
title_fullStr	Chromatin accessibility data sets show bias due to sequence specificity of the DNase I enzyme.
title_full_unstemmed	Chromatin accessibility data sets show bias due to sequence specificity of the DNase I enzyme.
title_sort	chromatin accessibility data sets show bias due to sequence specificity of the dnase i enzyme.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/07f3562fbdd9490287ef1b6281a41eec
work_keys_str_mv	AT hashemkoohy chromatinaccessibilitydatasetsshowbiasduetosequencespecificityofthednaseienzyme AT thomasadown chromatinaccessibilitydatasetsshowbiasduetosequencespecificityofthednaseienzyme AT timjhubbard chromatinaccessibilitydatasetsshowbiasduetosequencespecificityofthednaseienzyme
_version_	1718420944156884992

Chromatin accessibility data sets show bias due to sequence specificity of the DNase I enzyme.

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