Dataset Information

Profiling DNA methylation differences between inbred mouse strains on the Illumina Human Infinium MethylationEPIC microarray.

ABSTRACT: The Illumina Infinium MethylationEPIC provides an efficient platform for profiling DNA methylation in humans at over 850,000 CpGs. Model organisms such as mice do not currently benefit from an equivalent array. Here we used this array to measure DNA methylation in mice. We defined probes targeting conserved regions and performed differential methylation analysis and compared between the array-based assay and affinity-based DNA sequencing of methyl-CpGs (MBD-seq) and reduced representation bisulfite sequencing. Mouse samples consisted of 11 liver DNA from two strains, C57BL/6J (B6) and DBA/2J (D2), that varied widely in age. Linear regression was applied to detect differential methylation. In total, 13,665 probes (1.6% of total probes) aligned to conserved CpGs. Beta-values (?-value) for these probes showed a distribution similar to that in humans. Overall, there was high concordance in methylation signal between the EPIC array and MBD-seq (Pearson correlation r = 0.70, p-value < 0.0001). However, the EPIC probes had higher quantitative sensitivity at CpGs that are hypo- (?-value < 0.3) or hypermethylated (?-value > 0.7). In terms of differential methylation, no EPIC probe detected a significant difference between age groups at a Benjamini-Hochberg threshold of 10%, and the MBD-seq performed better at detecting age-dependent change in methylation. However, the top most significant probe for age (cg13269407; uncorrected p-value = 1.8 x 10-5) is part of the clock CpGs used to estimate the human epigenetic age. For strain, 219 EPIC probes detected significant differential methylation (FDR cutoff 10%) with ~80% CpGs associated with higher methylation in D2. This higher methylation profile in D2 compared to B6 was also replicated by the MBD-seq data. To summarize, we found only a small subset of EPIC probes that target conserved sites. However, for this small subset the array provides a reliable assay of DNA methylation and can be effectively used to measure differential methylation in mice.

SUBMITTER: Gujar H

PROVIDER: S-EPMC5846735 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Profiling DNA methylation differences between inbred mouse strains on the Illumina Human Infinium MethylationEPIC microarray.

Gujar Hemant H Liang Jane W JW Wong Nicholas C NC Mozhui Khyobeni K

PloS one 20180312 3

The Illumina Infinium MethylationEPIC provides an efficient platform for profiling DNA methylation in humans at over 850,000 CpGs. Model organisms such as mice do not currently benefit from an equivalent array. Here we used this array to measure DNA methylation in mice. We defined probes targeting conserved regions and performed differential methylation analysis and compared between the array-based assay and affinity-based DNA sequencing of methyl-CpGs (MBD-seq) and reduced representation bisulf ...[more]

PMID: 29529061

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Project description:DNA methylation age (DNAm age) has become a widely utilized epigenetic biomarker for the aging process. The Horvath method for determining DNAm age is perhaps the most widely utilized and validated DNA methylation age assessment measure. Horvath DNAm age is calculated based on methylation measurements at 353 loci, present on Illumina's 450k and 27k DNA methylation microarrays. With increasing use of the more recently developed Illumina MethylationEPIC (850k) microarray, it is worth revisiting this aging measure to evaluate estimation differences due to array design. Of the requisite 353 loci, 17 are missing from the 850k microarray. Similarly, an alternate, 71 loci DNA methylation age assessment measure created by Hannum et al. is missing 6 requisite loci. Using 17 datasets with 27k, 450k, and/or 850k methylation data, we compared each sample's epigenetic age estimated from all 353 loci required by the Horvath DNAm age calculator, and using only the 336 loci available on the 850k array. In 450k/27k data, removing loci not on the 850k array resulted in underestimation of Horvath's DNAm age. Underestimation of Horvath DNAm age increased from ages 0 to ~20, remaining stable thereafter (mean deviation = -3.46 y, SD = 1.13 for individuals ≥20 years). Underestimation of Horvath's DNAm age by the reduced 450k/27k data was similar to the underestimation observed in the 850k data indicating it is driven by missing probes. In analogous examination of Hannum's DNAm age, the magnitude and direction of epigenetic age misestimation varied with chronological age. In conclusion, inter-array deviations in DNAm age estimations may be largely driven by missing probes between arrays, despite default probe imputation procedures. Though correlations and associations based on Horvath's DNAm age may be unaffected, researchers should exercise caution when interpreting results based on absolute differences in DNAm age or when mixing samples assayed on different arrays.

Dataset Information

Profiling DNA methylation differences between inbred mouse strains on the Illumina Human Infinium MethylationEPIC microarray.

Publications

Profiling DNA methylation differences between inbred mouse strains on the Illumina Human Infinium MethylationEPIC microarray.

Similar Datasets

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