Genome-wide DNA methylation profiling in human breast tissue by illumina TruSeq methyl capture EPIC sequencing and infinium methylationEPIC beadchip microarray

A newly-developed platform, the Illumina TruSeq Methyl Capture EPIC library prep (TruSeq EPIC), builds on the content of the Infinium MethylationEPIC Beadchip Microarray (EPIC-array) and leverages the power of next-generation sequencing for targeted bisulphite sequencing. We empirically examined the performance of TruSeq EPIC and EPIC-array in assessing genome-wide DNA methylation in breast tissue samples. TruSeq EPIC provided data with a much higher density in the regions when compared to EPIC-array (similar to 2.74 million CpGs with at least 10X coverage vs similar to 752 K CpGs, respectively). Approximately 398 K CpGs were common and measured across the two platforms in every sample. Overall, there was high concordance in methylation levels between the two platforms (Pearson correlation r = 0.98, P < 0.0001). However, we observed that TruSeq EPIC measurements provided a wider dynamic range and likely a higher quantitative sensitivity for CpGs that were either hypo- or hyper-methylated (beta close to 0 or 1, respectively). In addition, when comparing different breast tissue types TruSeq EPIC identified more differentially methylated CpGs than EPIC-array, not only out of additional sites interrogated by TruSeq EPIC alone, but also out of common sites interrogated by both platforms. Our results suggest that both platforms show high reproducibility and reliability in genome-wide DNA methylation profiling, while TruSeq EPIC had a significant improvement over EPIC-array regarding genomic resolution and coverage. The wider dynamic range and likely higher precision of the estimates by the TruSeq EPIC may lead to the identification of novel differentially methylated markers that are associated with disease risk.

Automated summary

The newly developed Illumina TruSeq Methyl Capture EPIC library prep platform showed higher density data and wider dynamic range compared to the Infinium MethylationEPIC Beadchip Microarray. Both platforms demonstrated high concordance in methylation levels, but TruSeq EPIC offered improved genomic resolution and coverage, potentially leading to the identification of novel differentially methylated markers associated with disease risk.