title: Critical evaluation of the Illumina MethylationEPIC BeadChip microarray for whole-genome DNA methylation profiling.
abstract: In recent years the Illumina HumanMethylation450 (HM450) BeadChip has provided a user-friendly platform to profile DNA methylation in human samples. However, HM450 lacked 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.
  
  
  
  EPIC covers over 850,000 CpG sites, including >90 % of the CpGs from the HM450 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 provide an annotated list of probes whose signal could be affected by cross-hybridisation or underlying genetic variation.
  
  
  
  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.
authors.affiliation: Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, 2010, NSW, Australia.|St Vincent's Clinical School, University of NSW, Sydney, 2010, NSW, Australia.
authors.forename: Ruth
authors.initials: R
authors.lastname: Pidsley
authors.affiliation: Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, 2010, NSW, Australia.|St Vincent's Clinical School, University of NSW, Sydney, 2010, NSW, Australia.
authors.forename: Elena
authors.initials: E
authors.lastname: Zotenko
authors.affiliation: Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, 2010, NSW, Australia.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Peters
authors.affiliation: Prostate Research Group, Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash Partners Comprehensive Cancer Consortium, Monash University, Clayton, Melbourne, VIC, 3800, Australia.
authors.forename: Mitchell G
authors.initials: MG
authors.lastname: Lawrence
authors.affiliation: Prostate Research Group, Department of Anatomy and Developmental Biology, Biomedicine Discovery Institute, Monash Partners Comprehensive Cancer Consortium, Monash University, Clayton, Melbourne, VIC, 3800, Australia.
authors.forename: Gail P
authors.initials: GP
authors.lastname: Risbridger
authors.affiliation: CSIRO, Health and Biosecurity, PO Box 52, North Ryde, NSW, 1670, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Molloy
authors.affiliation: CSIRO, Health and Biosecurity, PO Box 52, North Ryde, NSW, 1670, Australia.
authors.forename: Susan
authors.initials: S
authors.lastname: Van Djik
authors.affiliation: FOODplus Research Centre, Department of Food and Wine Science, School of Agriculture Food and Wine, Waite Campus, The University of Adelaide, Adelaide, SA, Australia.|Child Nutrition Research Centre, South Australian Health and Medical Research Institute, Adelaide, SA, Australia.
authors.forename: Beverly
authors.initials: B
authors.lastname: Muhlhausler
authors.affiliation: Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, 2010, NSW, Australia.|St Vincent's Clinical School, University of NSW, Sydney, 2010, NSW, Australia.
authors.forename: Clare
authors.initials: C
authors.lastname: Stirzaker
authors.affiliation: Epigenetics Research Laboratory, Genomics and Epigenetics Division, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, 2010, NSW, Australia. s.clark@garvan.org.au.|St Vincent's Clinical School, University of NSW, Sydney, 2010, NSW, Australia. s.clark@garvan.org.au.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Clark
mesh_terms: D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D004742:Enhancer Elements, Genetic / Q000235:genetics; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D017422:Sequence Analysis, DNA / Q000379:methods*
keywords: DNA methylation; EPIC; Enhancers; HM450; Microarray; Validation; Whole-genome bisulphite sequencing (WGBS)