Critical evaluation of the Illumina MethylationEPIC BeadChip microarray for whole-genome DNA methylation profiling — ASN Events
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  3. Critical evaluation of the Illumina MethylationEPIC BeadChip microarray for whole-genome DNA methylation profiling

Critical evaluation of the Illumina MethylationEPIC BeadChip microarray for whole-genome DNA methylation profiling (#221)

Ruth Pidsley 1 , Elena Zotenko 1 , Timothy J Peters 1 , Mitchell G Lawrence 2 , Gail P Risbridger 2 , Peter Molloy 3 , Susan Van Dijk 3 , Beverly Muhlhausler 4 , Clare Stirzaker 1 , Susan Clark 1
  1. Genomics and Epigenetic Division, Garvan Institute, Darlinghurst, NSW, Australia
  2. Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia
  3. CSIRO, Sydney, NSW, Australia
  4. School of Agriculture Food and Wine, The University of Adelaide, Adelaide, South Australia, Australia

Mapping of human methylomes provides essential insight into the genomic location and mechanisms of methylation change in normal biological processes and disease. The Illumina HumanMethylation450 (HM450) BeadChip has to date provided a user-friendly platform to profile DNA methylation in human samples. However, HM450 methylation data has been limited by lack of coverage of distal regulatory elements. Illumina have now released the MethylationEPIC (EPIC) BeadChip, with new content specifically designed to target these regions. We have used HM450 and whole genome bisulphite sequencing (WGBS) to perform a critical evaluation of the new EPIC array platform (1).

EPIC covers over 850,000 CpG sites, including >90% of the CpGs from the HumanMethylation450 (HM450) BeadChip and an additional 413,743 CpGs. Even though the additional probes improve the coverage of regulatory elements, including 58% of FANTOM5 enhancers, only 7% distal and 27% proximal ENCODE regulatory elements are represented. Detailed comparisons of regulatory elements from EPIC and WGBS show that a single EPIC probe is not always informative for those distal regulatory elements showing variable methylation across the region. However, overall data from the EPIC array at single loci are highly reproducible across technical and biological replicates and demonstrate high correlation with HM450 and WGBS data. We show that the HM450 and EPIC arrays distinguish differentially methylated probes, but the absolute agreement depends on the threshold set for each platform. Finally, we have generated annotated lists of probes whose signal could be affected by cross-hybridisation or underlying genetic variation, which will be an important resource for the genomics and epigenetics community.

In conclusion we find that the EPIC array is a significant improvement over the HM450 array, with increased genome coverage of regulatory regions and high reproducibility and reliability, providing a valuable tool for high-throughput human methylome analyses from diverse clinical samples.

 

 

  1. Pidsley R, Zotenko E et al Genome Biology 2016
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