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

Hemant Gujar, Jane W. Liang, Nicholas C. Wong, Khyobeni Mozhui

Research output: Contribution to journalArticle

3 Citations (Scopus)

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 (β-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- (β-value < 0.3) or hypermethylated (β-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.

Original languageEnglish (US)
Article number0193496
JournalPloS one
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2018

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Inbred Strains Mice
Methylation
DNA methylation
DNA Methylation
Microarrays
methylation
mice
Assays
bisulfites
DNA
assays
DNA Sequence Analysis
Linear regression
Epigenomics
epigenetics
Liver
Clocks
Linear Models
sequence analysis
Age Groups

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Profiling DNA methylation differences between inbred mouse strains on the Illumina Human Infinium MethylationEPIC microarray. / Gujar, Hemant; Liang, Jane W.; Wong, Nicholas C.; Mozhui, Khyobeni.

In: PloS one, Vol. 13, No. 3, 0193496, 01.03.2018.

Research output: Contribution to journalArticle

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