DNA methylation profiling: comparison of genome-wide sequencing methods and the Infinium HumanMethylation450 BeadChip

Aims: To compare the performance of four sequence-based and one microarray methods for DNA methylation profiling. Methods: DNA from two cell lines were profiled by reduced representation bisulfite sequencing, methyl capture sequencing (SS-Meth Seq), NimbleGen SeqCapEpi CpGiant (Nimblegen MethSeq), methylated DNA immunoprecipitation (MeDIP) and the Human Methylation 450 Bead Chip (Meth450K). Results & conclusion: Despite differences in genome-wide coverage, high correlation and concordance were observed between different methods. Significant overlap of differentially methylated regions was identified between sequenced-based platforms. MeDIP provided the best coverage for the whole genome and gene body regions, while RRBS and Nimblegen MethSeq were superior for CpGs in CpG islands and promoters. Methylation analyses can be achieved by any of the five methods but understanding their differences may better address the research question being posed.