Comparison of Methyl-capture Sequencing vs. Infinium 450K methylation array for methylome analysis in clinical samples.

TitleComparison of Methyl-capture Sequencing vs. Infinium 450K methylation array for methylome analysis in clinical samples.
Publication TypeJournal Article
Year of Publication2016
AuthorsTeh ALing, Pan H, Lin X, Lim YIves, Patro CPawan Kuma, Cheong CYujing, Gong M, MacIsaac JL, Kwoh C-K, Meaney MJ, Kobor MS, Chong Y-S, Gluckman PD, Holbrook JD, Karnani N
JournalEpigenetics
Volume11
Issue1
Pagination36-48
Date Published2016
ISSN1559-2308
KeywordsDNA Methylation, Epigenesis, Genetic, Ethnic Groups, Female, Genome, Human, Humans, Male, Oligonucleotide Array Sequence Analysis, Sequence Alignment, Sequence Analysis, DNA
Abstract

Interindividual variability in the epigenome has gained tremendous attention for its potential in pathophysiological investigation, disease diagnosis, and evaluation of clinical intervention. DNA methylation is the most studied epigenetic mark in epigenome-wide association studies (EWAS) as it can be detected from limited starting material. Infinium 450K methylation array is the most popular platform for high-throughput profiling of this mark in clinical samples, as it is cost-effective and requires small amounts of DNA. However, this method suffers from low genome coverage and errors introduced by probe cross-hybridization. Whole-genome bisulfite sequencing can overcome these limitations but elevates the costs tremendously. Methyl-Capture Sequencing (MC Seq) is an attractive intermediate solution to increase the methylome coverage in large sample sets. Here we first demonstrate that MC Seq can be employed using DNA amounts comparable to the amounts used for Infinium 450K. Second, to provide guidance when choosing between the 2 platforms for EWAS, we evaluate and compare MC Seq and Infinium 450K in terms of coverage, technical variation, and concordance of methylation calls in clinical samples. Last, since the focus in EWAS is to study interindividual variation, we demonstrate the utility of MC Seq in studying interindividual variation in subjects from different ethnicities.

DOI10.1080/15592294.2015.1132136
Alternate JournalEpigenetics
PubMed ID26786415
PubMed Central IDPMC4846133

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