Quantitative comparison of genome-wide DNA methylation mapping technologies


DNA methylation plays a key role in regulating eukaryotic gene expression. Although mitotically heritable and stable over time, patterns of DNA methylation frequently change in response to cell differentiation, disease and environmental influences. Several methods have been developed to map DNA methylation on a genomic scale. Here, we benchmark four of these approaches by analyzing two human embryonic stem cell lines derived from genetically unrelated embryos and a matched pair of colon tumor and adjacent normal colon tissue obtained from the same donor. Our analysis reveals that methylated DNA immunoprecipitation sequencing (MeDIP-seq), methylated DNA capture by affinity purification (MethylCap-seq), reduced representation bisulfite sequencing (RRBS) and the Infinium HumanMethylation27 assay all produce accurate DNA methylation data. However, these methods differ in their ability to detect differentially methylated regions between pairs of samples. We highlight strengths and weaknesses of the four methods and give practical recommendations for the design of epigenomic case-control studies.


Each of the links below opens DNA methylation tracks in the UCSC Genome Browser. The MeDIP and MethylCap tracks can be read like ChIP-seq tracks, while the RRBS and Infinium tracks display absolute DNA methylation levels at single CpGs. For RRBS we find it most convenient to view the data in "squish" mode, such that CpGs are stacked on top of each other and darker levels of blue correspond to higher methylation levels. Further explanation of the data format is available from the legend of Figure 1 in the paper.

Sample / Method MeDIP MethylCap RRBS Infinium
HUES6 ES cell line view HUES6.MeDIP view HUES6.MethylCap view HUES6.RRBS view HUES6.Infinium
HUES8 ES cell line view HUES8.MeDIP view HUES8.MethylCap view HUES8.RRBS view HUES8.Infinium
Primary colon tumor view Colon_tumor.MeDIP view Colon_tumor.MethylCap view Colon_tumor.RRBS view Colon_tumor.Infinium
Primary colon tumor view Colon_normal.MeDIP view Colon_normal.MethylCap view Colon_normal.RRBS view Colon_normal.Infinium



Bock C, Tomazou E, Brinkman AB, Müller F, Simmer F, Gu H, Jäger N, Gnirke A, Stunnenberg H, Meissner A (2010). Quantitative comparison of genome-wide DNA methylation mapping technologies, Nat Biotechnol 28, 1106-1114.

Summarized in a News & Views article in the same issue of Nature Biotechnology