Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/102253
Citations
Scopus Web of Science® Altmetric
?
?
Type: Journal article
Title: Critical evaluation of the Illumina MethylationEPIC BeadChip microarray for whole-genome DNA methylation profiling
Author: Pidsley, R.
Zotenko, E.
Peters, T.
Lawrence, M.
Risbridger, G.
Molloy, P.
Van Djik, S.
Muhlhausler, B.
Stirzaker, C.
Clark, S.
Citation: Genome Biology, 2016; 17(1):208-1-208-17
Publisher: BioMed Central
Issue Date: 2016
ISSN: 1474-7596
1474-760X
Statement of
Responsibility: 
Ruth Pidsley, Elena Zotenko, Timothy J. Peters, Mitchell G. Lawrence, Gail P. Risbridger, Peter Molloy, Susan Van Djik, Beverly Muhlhausler, Clare Stirzaker and Susan J. Clark
Abstract: Background: 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. Results: 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. Conclusion: 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.
Keywords: EPIC; DNA methylation; HM450; Whole-genome bisulphite sequencing (WGBS); Microarray; Enhancers; Validation
Description: Published online: 7 October 2016
Rights: © 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
RMID: 0030057054
DOI: 10.1186/s13059-016-1066-1
Grant ID: http://purl.org/au-research/grants/nhmrc/1088144
http://purl.org/au-research/grants/nhmrc/1106870
http://purl.org/au-research/grants/nhmrc/1063559
http://purl.org/au-research/grants/nhmrc/1035721
http://purl.org/au-research/grants/nhmrc/1102752
Appears in Collections:Agriculture, Food and Wine publications

Files in This Item:
File Description SizeFormat 
hdl_102253.pdfPublished Version6.74 MBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.