Unique and assay specific features of NOMe-, ATAC- and DNase I-seq data. Nordström, K. J V, Schmidt, F., Gasparoni, N., Salhab, A., Gasparoni, G., Kattler, K., Müller, F., Ebert, P., Costa, I. G, consortium , D., Pfeifer, N., Lengauer, T., Schulz, M. H, & Walter, J. Nucleic Acids Research, 47(20):10580–10596, 10, 2019.
doi  abstract   bibtex   
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.
@article{Nordstroem.2019, 
year = {2019}, 
rating = {0}, 
title = {{Unique and assay specific features of NOMe-, ATAC- and DNase I-seq data}}, 
author = {Nordström, Karl J V and Schmidt, Florian and Gasparoni, Nina and Salhab, Abdulrahman and Gasparoni, Gilles and Kattler, Kathrin and Müller, Fabian and Ebert, Peter and Costa, Ivan G and consortium, DEEP and Pfeifer, Nico and Lengauer, Thomas and Schulz, Marcel H and Walter, Jörn}, 
journal = {Nucleic Acids Research}, 
issn = {0305-1048}, 
doi = {10.1093/nar/gkz799}, 
pmid = {31584093}, 
pmcid = {PMC6847574}, 
abstract = {{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.}}, 
pages = {10580--10596}, 
number = {20}, 
volume = {47}, 
language = {English}, 
month = {10}
}
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