Validation of a DNA methylation microarray for 850,000 CpG sites of the human genome enriched in enhancer sequences

DNA methylation is the most well-known epigenetic mark and CpG methylation is critical for many cellular processes and human disorders. Cancer has highlighted the relevance of an aberrant DNA methylation landscape, including promoter CpG island hypermethylation-associated silencing of tumor suppressor genes and the presence of DNA hypomethylation blocks, but an altered DNA methylome is also now evident in other pathologies. However, progresses in delivering complete DNA methylation maps are compromised by the high price and labor and interpretation-consuming aspects of the single nucleotide methods nowadays used for whole genome bisulfite sequencing analyses. Following the success of the industry-leading HumanMethylation450 BeadChip (Infinium) methylation microarray that assess close to 450,000 CpG sites (450K), we have biologically and technically validated the newly developed MethylationEPIC BeadChip (Infinium) microarray that covers over 850,000 CpG methylation sites (850K). The 850K microarray contains >90% of the original 450K methylation sites, but add new 350,000 CpGs located in enhancers regions identified by the ENCODE and FANTOM5 projects. Herein, we show that the 850K DNA methylation array demonstrates high reproducibility for the previously analyzed CpG sites included in the 450K microarray; it is consistent among technical replicates; it is reliable in the matched study of fresh frozen vs formalin-fixed paraffin-embeded samples; and it is useful for both 5-methylcytosine and 5-hydroxymethylcytosine determination. The provided validation milestones highlights the value of the MethylationEPIC BeadChip as an informative and useful tool for the analyses of the DNA methylation profile of the human genome.