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Information recovery from low coverage whole-genome bisulfite sequencing.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Libertini, Emanuele 
Hamoudi, Rifat A 
Gut, Marta 
Ziller, Michael J 

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.

Description

Keywords

Algorithms, Computational Biology, CpG Islands, DNA Methylation, Genome, Human, Genotype, Haplotypes, Humans, Reproducibility of Results, Sulfites, Whole Genome Sequencing

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

7

Publisher

Springer Science and Business Media LLC
Sponsorship
European Commission (282510)
European Commission (257082)
British Heart Foundation (None)
British Heart Foundation (None)
CCF (None)