@article{4fe0bdff07124069818039ec9d120edd,
title = "Information recovery from low coverage whole-genome bisulfite sequencing",
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 {\^a}1/430% 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.",
author = "Emanuele Libertini and Heath, {Simon C.} and Hamoudi, {Rifat A.} and Marta Gut and Ziller, {Michael J.} and Agata Czyz and Victor Ruotti and Stunnenberg, {Hendrik G.} and Mattia Frontini and Ouwehand, {Willem H.} and Alexander Meissner and Gut, {Ivo G.} and Stephan Beck",
note = "Funding Information: We gratefully acknowledge the participation of all NIHR Cambridge BioResource volunteers. We thank the Cambridge BioResource staff for their help with volunteer recruitment. We thank members of the Cambridge BioResource SAB and Management Committee for their support of our study and the National Institute for Health Research Cambridge Biomedical Research Centre for funding. Mattia Frontini was supported by the BHF Cambridge Centre of Excellence [RE/13/6/30180]. Research in the Ouwehand laboratory is supported by EU-FP7 project BLUEPRINT (282510) and by program grants from the National Institute for Health Research (NIHR, http://www.nihr.ac.uk); and the British Heart Foundation under numbers RP-PG-0310-1002 and RG/09/12/28096 (http://www.bhf.org.uk). The laboratory receives funding from the NHS Blood and Transplant for facilities. EL and SB were supported by EU-FP7 projects EpiTrain (316758), EpiGeneSys (257082) and BLUEPRINT (282510), the Wellcome Trust (99148) and a Royal Society Wolfson Research Merit Award (WM100023).",
year = "2016",
month = jun,
day = "27",
doi = "10.1038/ncomms11306",
language = "English",
volume = "7",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Research",
}