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Publication Detail

Title: Saliva cell type DNA methylation reference panel for epidemiological studies in children.

Authors: Middleton, Lauren Y M; Dou, John; Fisher, Jonah; Heiss, Jonathan A; Nguyen, Vy K; Just, Allan C; Faul, Jessica; Ware, Erin B; Mitchell, Colter; Colacino, Justin A; M Bakulski, Kelly

Published In Epigenetics, (2022 Jan-Feb)

Abstract: Saliva is a widely used biological sample, especially in pediatric research, containing a heterogenous mixture of immune and epithelial cells. Associations of exposure or disease with saliva DNA methylation can be influenced by cell-type proportions. Here, we developed a saliva cell-type DNA methylation reference panel to estimate interindividual cell-type heterogeneity in whole saliva studies. Saliva was collected from 22 children (7-16 years) and sorted into immune and epithelial cells, using size exclusion filtration and magnetic bead sorting. DNA methylation was measured using the Illumina MethylationEPIC BeadChip. We assessed cell-type differences in DNA methylation profiles and tested for enriched biological pathways. Immune and epithelial cells differed at 181,577 (22.8%) DNA methylation sites (t-test p < 6.28 × 10-8). Immune cell hypomethylated sites are mapped to genes enriched for immune pathways (p < 3.2 × 10-5). Epithelial cell hypomethylated sites were enriched for cornification (p = 5.2 × 10-4), a key process for hard palette formation. Saliva immune and epithelial cells have distinct DNA methylation profiles which can drive whole-saliva DNA methylation measures. A primary saliva DNA methylation reference panel, easily implemented with an R package, will allow estimates of cell proportions from whole saliva samples and improve epigenetic epidemiology studies by accounting for measurement heterogeneity by cell-type proportions.

PubMed ID: 33588693 Exiting the NIEHS site

MeSH Terms: Child; CpG Islands; DNA Methylation*; Epidemiologic Studies; Epigenesis, Genetic; Epigenomics; Humans; Saliva*

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