Inherent signals in sequencing-based Chromatin-ImmunoPrecipitation control libraries.

<h4>Background</h4>The growth of sequencing-based Chromatin Immuno-Precipitation studies call for a more in-depth understanding of the nature of the technology and of the resultant data to reduce false positives and false negatives. Control libraries are typically constructed to compleme...

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Autores principales:	Vinsensius B Vega, Edwin Cheung, Nallasivam Palanisamy, Wing-Kin Sung
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ebaddad6d14446729353857f92cec375
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spelling	oai:doaj.org-article:ebaddad6d14446729353857f92cec3752021-11-25T06:16:08ZInherent signals in sequencing-based Chromatin-ImmunoPrecipitation control libraries.1932-620310.1371/journal.pone.0005241https://doaj.org/article/ebaddad6d14446729353857f92cec3752009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19367334/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The growth of sequencing-based Chromatin Immuno-Precipitation studies call for a more in-depth understanding of the nature of the technology and of the resultant data to reduce false positives and false negatives. Control libraries are typically constructed to complement such studies in order to mitigate the effect of systematic biases that might be present in the data. In this study, we explored multiple control libraries to obtain better understanding of what they truly represent.<h4>Methodology</h4>First, we analyzed the genome-wide profiles of various sequencing-based libraries at a low resolution of 1 Mbp, and compared them with each other as well as against aCGH data. We found that copy number plays a major influence in both ChIP-enriched as well as control libraries. Following that, we inspected the repeat regions to assess the extent of mapping bias. Next, significantly tag-rich 5 kbp regions were identified and they were associated with various genomic landmarks. For instance, we discovered that gene boundaries were surprisingly enriched with sequenced tags. Further, profiles between different cell types were noticeably distinct although the cell types were somewhat related and similar.<h4>Conclusions</h4>We found that control libraries bear traces of systematic biases. The biases can be attributed to genomic copy number, inherent sequencing bias, plausible mapping ambiguity, and cell-type specific chromatin structure. Our results suggest careful analysis of control libraries can reveal promising biological insights.Vinsensius B VegaEdwin CheungNallasivam PalanisamyWing-Kin SungPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 4, p e5241 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vinsensius B Vega Edwin Cheung Nallasivam Palanisamy Wing-Kin Sung Inherent signals in sequencing-based Chromatin-ImmunoPrecipitation control libraries.
description	<h4>Background</h4>The growth of sequencing-based Chromatin Immuno-Precipitation studies call for a more in-depth understanding of the nature of the technology and of the resultant data to reduce false positives and false negatives. Control libraries are typically constructed to complement such studies in order to mitigate the effect of systematic biases that might be present in the data. In this study, we explored multiple control libraries to obtain better understanding of what they truly represent.<h4>Methodology</h4>First, we analyzed the genome-wide profiles of various sequencing-based libraries at a low resolution of 1 Mbp, and compared them with each other as well as against aCGH data. We found that copy number plays a major influence in both ChIP-enriched as well as control libraries. Following that, we inspected the repeat regions to assess the extent of mapping bias. Next, significantly tag-rich 5 kbp regions were identified and they were associated with various genomic landmarks. For instance, we discovered that gene boundaries were surprisingly enriched with sequenced tags. Further, profiles between different cell types were noticeably distinct although the cell types were somewhat related and similar.<h4>Conclusions</h4>We found that control libraries bear traces of systematic biases. The biases can be attributed to genomic copy number, inherent sequencing bias, plausible mapping ambiguity, and cell-type specific chromatin structure. Our results suggest careful analysis of control libraries can reveal promising biological insights.
format	article
author	Vinsensius B Vega Edwin Cheung Nallasivam Palanisamy Wing-Kin Sung
author_facet	Vinsensius B Vega Edwin Cheung Nallasivam Palanisamy Wing-Kin Sung
author_sort	Vinsensius B Vega
title	Inherent signals in sequencing-based Chromatin-ImmunoPrecipitation control libraries.
title_short	Inherent signals in sequencing-based Chromatin-ImmunoPrecipitation control libraries.
title_full	Inherent signals in sequencing-based Chromatin-ImmunoPrecipitation control libraries.
title_fullStr	Inherent signals in sequencing-based Chromatin-ImmunoPrecipitation control libraries.
title_full_unstemmed	Inherent signals in sequencing-based Chromatin-ImmunoPrecipitation control libraries.
title_sort	inherent signals in sequencing-based chromatin-immunoprecipitation control libraries.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/ebaddad6d14446729353857f92cec375
work_keys_str_mv	AT vinsensiusbvega inherentsignalsinsequencingbasedchromatinimmunoprecipitationcontrollibraries AT edwincheung inherentsignalsinsequencingbasedchromatinimmunoprecipitationcontrollibraries AT nallasivampalanisamy inherentsignalsinsequencingbasedchromatinimmunoprecipitationcontrollibraries AT wingkinsung inherentsignalsinsequencingbasedchromatinimmunoprecipitationcontrollibraries
_version_	1718414017290043392

Inherent signals in sequencing-based Chromatin-ImmunoPrecipitation control libraries.

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