Battle of epigenetic proportions: comparing Illumina's EPIC methylation microarrays and TruSeq targeted bisulfite sequencing

Abstract

DNA methylation microarrays have been the platform of choice for epigenome-wide association studies in epidemiology, but declining costs have rendered targeted bisulphite sequencing a feasible alternative. Nonetheless, the literature for researchers seeking guidance on which platform to choose is sparse. To fill this gap, we conducted a comparison study in which we processed cord blood samples from four newborns in duplicates using both the Illumina HumanMethylationEPIC BeadChip and the Illumina TruSeq Methyl Capture EPIC Kit, and evaluated both platforms in regard to coverage, reproducibility, and identification of differential methylation. We conclude that with current analytic goals microarrays still outperform bisulphite sequencing for precise quantification of DNA methylation.

Keywords: DNA methylation; EWAS; bisulphite sequencing; comparison of experimental platforms; microarray.

Figure 1.

Coverage of epigenetic and genetic elements for EPIC (black) and TruSeq (red).

Figure 2.

Concordance of methylation level estimates between EPIC and TruSeq samples stratified by read depth.