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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
Source :
Epigenetics; Jan/Feb2022, Vol. 17 Issue 2, p161-177, 17p
Publication Year :
2022

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<superscript>−8</superscript>). Immune cell hypomethylated sites are mapped to genes enriched for immune pathways (p < 3.2 × 10<superscript>−5</superscript>). Epithelial cell hypomethylated sites were enriched for cornification (p = 5.2 × 10<superscript>−4</superscript>), 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
15592294
Volume :
17
Issue :
2
Database :
Complementary Index
Journal :
Epigenetics
Publication Type :
Academic Journal
Accession number :
155377976
Full Text :
https://doi.org/10.1080/15592294.2021.1890874