Comparison of methylation capture sequencing and Infinium MethylationEPIC array in peripheral blood mononuclear cells
Year: 2020
Type: article
Abstract: BACKGROUND: Epigenome-wide association studies (EWAS) have been widely applied to identify methylation CpG sites associated with human disease. To date, the Infinium MethylationEPIC array (EPIC) is commonly used for high-throughput DNA methylation profiling. However, the EPIC array covers only 30% of the human methylome. Methylation Capture bisulfite sequencing (MC-seq) captures target regions of methylome and has advantages of extensive coverage in the methylome at an affordable price. METHODS: Epigenome-wide DNA methylation in four peripheral blood mononuclear cell samples was profiled by using SureSelectXT Methyl-Seq for MC-seq and EPIC platforms separately. CpG site-based reproducibility of MC-seq was assessed with DNA sample inputs ranging in quantity of high (> 1000 ng), medium (300-1000 ng), and low (150 ng-300 ng). To compare the performance of MC-seq and the EPIC arrays, we conducted a Pearson correlation and methylation value difference at each CpG site that was detected by both MC-seq and EPIC. We compared the percentage and counts in each CpG island and gene annotation between MC-seq and the EPIC array. RESULTS: After quality control, an average of 3,708,550 CpG sites per sample were detected by MC-seq with DNA quantity > 1000 ng. Reproducibility of DNA methylation in MC-seq-detected CpG sites was high among samples with high, medium, and low DNA inputs (r > 0.96). The EPIC array captured an average of 846,464 CpG sites per sample. Compared with the EPIC array, MC-seq detected more CpGs in coding regions and CpG islands. Among the 472,540 CpG sites captured by both platforms, methylation of a majority of CpG sites was highly correlated in the same sample (r: 0.98-0.99). However, methylation for a small proportion of CpGs (N = 235) differed significantly between the two platforms, with differences in beta values of greater than 0.5. CONCLUSIONS: Our results show that MC-seq is an efficient and reliable platform for methylome profiling with a broader coverage of the methylome than the array-based platform. Although methylation measurements in majority of CpGs are highly correlated, a number of CpG sites show large discrepancy between the two platforms, which warrants further investigation and needs cautious interpretation.
Source: Epigenetics & Chromatin
Authors: Chang Shu, Xinyu Zhang, Bradley E. Aouizerat, Ke Xu
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,790
Awards: G2674688597, Feature selection of DNA methylation biosignatures for neuropathy with comorbid drug abuse in the setting of HIV infection, Defining the impact of injection drug use on antiretroviral therapy and HIV treatment outcomes: an (epi)genomic approach, Genome-wide DNA methylation in HIV infected drug users, Methylome-wide and mQTL analysis of HIV progression in the context of cocaine use, Enhancing Discovery of HIV Host Genetics using Drug Abuse and other Interactions, In vivo study of THC-induced immunogenome changes at single cell resolution in HIV-infected humans, Yale Clinical and Translational Science Award
OpenAlex ID: W3107798130