Abstract
BackgroundBase-resolution methylome data generated by whole-genome bisulfite sequencing (WGBS) is often used to segment the genome into domains with distinct methylation levels. However, most segmentation methods include many parameters to be carefully tuned and/or fail to exploit the unsurpassed resolution of the data. Furthermore, there is no simple method that displays the composition of the domains to grasp global trends in each methylome.ResultsWe propose to use changepoint detection for domain demarcation based on base-resolution methylome data. While the proposed method segments the methylome in a largely comparable manner to conventional approaches, it has only a single parameter to be tuned. Furthermore, it fully exploits the base-resolution of the data to enable simultaneous detection of methylation changes in even contrasting size ranges, such as focal hypermethylation and global hypomethylation in cancer methylomes. We also propose a simple plot termed methylated domain landscape (MDL) that globally displays the size, the methylation level and the number of the domains thus defined, thereby enabling one to intuitively grasp trends in each methylome. Since the pattern of MDL often reflects cell lineages and is largely unaffected by data size, it can serve as a novel signature of methylome.ConclusionsChangepoint detection in base-resolution methylome data followed by MDL plotting provides a novel method for methylome characterization and will facilitate global comparison among various WGBS data differing in size and even species origin.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1809-5) contains supplementary material, which is available to authorized users.
Highlights
Base-resolution methylome data generated by whole-genome bisulfite sequencing (WGBS) is often used to segment the genome into domains with distinct methylation levels
Changepoint detection in base-resolution methylome data To test whether changepoint detection can define the boundaries of a domain with a distinct methylation level from base-resolution methylome data, we used the WGBS data of human embryonic stem cell (ESC) H1 and human lung fibroblast IMR90 [4]
While the ESC methylome includes a substantial number of methylated non-CpG sites, this study focuses on CpG sites, the major targets of mammalian DNA methylation
Summary
Base-resolution methylome data generated by whole-genome bisulfite sequencing (WGBS) is often used to segment the genome into domains with distinct methylation levels. Most segmentation methods include many parameters to be carefully tuned and/or fail to exploit the unsurpassed resolution of the data. Recent advent of next-generation sequencing technologies has enabled whole-genome bisulfite sequencing (WGBS) to provide highly quantitative methylation data for every cytosine residue in the genome [1, 2]. The base-resolution methylome data is used to segment the methylome into domains with distinct methylation levels. It had been thought that vertebrate genomes are globally methylated to a high level but punctuated with small unmethylated regions, which often include promoters, enhancers, CpG islands and so on [3]. WGBS has confirmed this notion but led to finer
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