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Unique and assay specific features of NOMe-, ATAC- and DNase I-seq data

Chromatin accessibility maps are important for the functional interpretation of the genome. Here, we systematically analysed assay specific differences between DNase I-seq, ATAC-seq and NOMe-seq in a side by side experimental and bioinformatic setup. We observe that most prominent nucleosome deplete...

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Autores principales: Nordström, Karl J V, Schmidt, Florian, Gasparoni, Nina, Salhab, Abdulrahman, Gasparoni, Gilles, Kattler, Kathrin, Müller, Fabian, Ebert, Peter, Costa, Ivan G, Pfeifer, Nico, Lengauer, Thomas, Schulz, Marcel H, Walter, Jörn
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6847574/
https://www.ncbi.nlm.nih.gov/pubmed/31584093
http://dx.doi.org/10.1093/nar/gkz799
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author Nordström, Karl J V
Schmidt, Florian
Gasparoni, Nina
Salhab, Abdulrahman
Gasparoni, Gilles
Kattler, Kathrin
Müller, Fabian
Ebert, Peter
Costa, Ivan G
Pfeifer, Nico
Lengauer, Thomas
Schulz, Marcel H
Walter, Jörn
author_facet Nordström, Karl J V
Schmidt, Florian
Gasparoni, Nina
Salhab, Abdulrahman
Gasparoni, Gilles
Kattler, Kathrin
Müller, Fabian
Ebert, Peter
Costa, Ivan G
Pfeifer, Nico
Lengauer, Thomas
Schulz, Marcel H
Walter, Jörn
author_sort Nordström, Karl J V
collection PubMed
description Chromatin accessibility maps are important for the functional interpretation of the genome. Here, we systematically analysed assay specific differences between DNase I-seq, ATAC-seq and NOMe-seq in a side by side experimental and bioinformatic setup. We observe that most prominent nucleosome depleted regions (NDRs, e.g. in promoters) are roboustly called by all three or at least two assays. However, we also find a high proportion of assay specific NDRs that are often ‘called’ by only one of the assays. We show evidence that these assay specific NDRs are indeed genuine open chromatin sites and contribute important information for accurate gene expression prediction. While technically ATAC-seq and DNase I-seq provide a superb high NDR calling rate for relatively low sequencing costs in comparison to NOMe-seq, NOMe-seq singles out for its genome-wide coverage allowing to not only detect NDRs but also endogenous DNA methylation and as we show here genome wide segmentation into heterochromatic B domains and local phasing of nucleosomes outside of NDRs. In summary, our comparisons strongly suggest to consider assay specific differences for the experimental design and for generalized and comparative functional interpretations.
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spelling pubmed-68475742019-11-18 Unique and assay specific features of NOMe-, ATAC- and DNase I-seq data Nordström, Karl J V Schmidt, Florian Gasparoni, Nina Salhab, Abdulrahman Gasparoni, Gilles Kattler, Kathrin Müller, Fabian Ebert, Peter Costa, Ivan G Pfeifer, Nico Lengauer, Thomas Schulz, Marcel H Walter, Jörn Nucleic Acids Res Gene regulation, Chromatin and Epigenetics Chromatin accessibility maps are important for the functional interpretation of the genome. Here, we systematically analysed assay specific differences between DNase I-seq, ATAC-seq and NOMe-seq in a side by side experimental and bioinformatic setup. We observe that most prominent nucleosome depleted regions (NDRs, e.g. in promoters) are roboustly called by all three or at least two assays. However, we also find a high proportion of assay specific NDRs that are often ‘called’ by only one of the assays. We show evidence that these assay specific NDRs are indeed genuine open chromatin sites and contribute important information for accurate gene expression prediction. While technically ATAC-seq and DNase I-seq provide a superb high NDR calling rate for relatively low sequencing costs in comparison to NOMe-seq, NOMe-seq singles out for its genome-wide coverage allowing to not only detect NDRs but also endogenous DNA methylation and as we show here genome wide segmentation into heterochromatic B domains and local phasing of nucleosomes outside of NDRs. In summary, our comparisons strongly suggest to consider assay specific differences for the experimental design and for generalized and comparative functional interpretations. Oxford University Press 2019-11-18 2019-10-04 /pmc/articles/PMC6847574/ /pubmed/31584093 http://dx.doi.org/10.1093/nar/gkz799 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Gene regulation, Chromatin and Epigenetics
Nordström, Karl J V
Schmidt, Florian
Gasparoni, Nina
Salhab, Abdulrahman
Gasparoni, Gilles
Kattler, Kathrin
Müller, Fabian
Ebert, Peter
Costa, Ivan G
Pfeifer, Nico
Lengauer, Thomas
Schulz, Marcel H
Walter, Jörn
Unique and assay specific features of NOMe-, ATAC- and DNase I-seq data
title Unique and assay specific features of NOMe-, ATAC- and DNase I-seq data
title_full Unique and assay specific features of NOMe-, ATAC- and DNase I-seq data
title_fullStr Unique and assay specific features of NOMe-, ATAC- and DNase I-seq data
title_full_unstemmed Unique and assay specific features of NOMe-, ATAC- and DNase I-seq data
title_short Unique and assay specific features of NOMe-, ATAC- and DNase I-seq data
title_sort unique and assay specific features of nome-, atac- and dnase i-seq data
topic Gene regulation, Chromatin and Epigenetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6847574/
https://www.ncbi.nlm.nih.gov/pubmed/31584093
http://dx.doi.org/10.1093/nar/gkz799
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