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  Information recovery from low coverage whole-genome bisulfite sequencing

Libertini, E., Heath, S. C., Hamoudi, R. A., Gut, M., Ziller, M. J., Czyz, A., et al. (2016). Information recovery from low coverage whole-genome bisulfite sequencing. Nature Communications, 2016: 7:11306. doi:10.1038/ncomms11306.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-DEB9-E Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-DEBA-C
Genre: Journal Article

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© 2016 Macmillan Publishers Limited, part of Springer Nature

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Libertini, Emanuele, Author
Heath, Simon C., Author
Hamoudi, Rifat A. , Author
Gut, Marta, Author
Ziller, Michael J., Author
Czyz, Agata, Author
Ruotti, Victor , Author
Stunnenberg, Hendrik G., Author
Frontini, Mattia , Author
Ouwehand, Willem H. , Author
Meissner, Alexander1, 2, Author              
Affiliations:
1Dept. of Genome Regulation (Head: Alexander Meissner), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2379694              
2Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge, Massachusetts 02138, USA, ou_persistent22              

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 Abstract: The cost of whole-genome bisulfite sequencing (WGBS) remains a bottleneck for many studies and it is therefore imperative to extract as much information as possible from a given dataset. This is particularly important because even at the recommend 30X coverage for reference methylomes, up to 50% of high-resolution features such as differentially methylated positions (DMPs) cannot be called with current methods as determined by saturation analysis. To address this limitation, we have developed a tool that dynamically segments WGBS methylomes into blocks of comethylation (COMETs) from which lost information can be recovered in the form of differentially methylated COMETs (DMCs). Using this tool, we demonstrate recovery of ∼30% of the lost DMP information content as DMCs even at very low (5X) coverage. This constitutes twice the amount that can be recovered using an existing method based on differentially methylated regions (DMRs). In addition, we explored the relationship between COMETs and haplotypes in lymphoblastoid cell lines of African and European origin. Using best fit analysis, we show COMETs to be correlated in a population-specific manner, suggesting that this type of dynamic segmentation may be useful for integrated (epi)genome-wide association studies in the future.

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Language(s): eng - English
 Dates: 2016-03-112016-06-27
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1038/ncomms11306
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Title: Nature Communications
  Abbreviation : Nat. Commun.
Source Genre: Journal
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Publ. Info: London : Nature Publishing Group
Pages: - Volume / Issue: 2016 Sequence Number: 7:11306 Start / End Page: - Identifier: ISSN: 2041-1723
CoNE: https://pure.mpg.de/cone/journals/resource/2041-1723