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

Comparison of Methyl-capture Sequencing vs. Infinium 450K methylation array for methylome analysis in clinical samples
Title:
Comparison of Methyl-capture Sequencing vs. Infinium 450K methylation array for methylome analysis in clinical samples
Other Titles:
Epigenetics
Publication Date:
22 February 2016
Citation:
Teh AL, Pan H, Lin X, Lim YI, Patro CP, Cheong CY, Gong M, MacIsaac JL, Kwoh CK, Meaney MJ, Kobor MS, Chong YS, Gluckman PD, Holbrook JD, Karnani N.” Comparison of Methyl-capture Sequencing vs. Infinium 450K methylation array for methylome analysis in clinical samples”. Epigenetics. 2016;11(1):36-48. doi: 10.1080/15592294.2015.1132136.
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.
License type:
http://creativecommons.org/licenses/by-nc/4.0/
Funding Info:
This work was supported by the Strategic Positioning Fund (SPF002_G00056) provided by the Agency for Science, Technology and Research (A*STAR), Singapore. Additional funds were provided by Singapore Institute for Clinical Sciences (SICS) –A*STAR.
Description:
ISSN:
1559-2294
1559-2308
Files uploaded: