Don't brush off buccal data heterogeneity

Epigenetics. 2019 Feb;14(2):109-117. doi: 10.1080/15592294.2019.1581592. Epub 2019 Mar 1.


Buccal epithelial cells are among the most clinically accessible tissues and are increasingly being used to identify epigenetic disease patterns. However, substantial variation in buccal DNA methylation patterns indicates heterogeneity of cell types within and between samples, raising questions of data quality. We systematically estimated cell-type composition for a large collection of buccal and saliva samples from 11 published studies of DNA methylation. In these we identified numerous cases of buccal samples with questionable purity, which may be affected by sampling from individuals with neurodevelopmental disorders, and by the brushes used for sample collection. Further challenges are involved in comparisons with tissues such as saliva, in which buccal component varies widely. We propose a reference-based method of correcting for buccal purity that reduces unwanted variation while preserving cross-tissue differences. Our work demonstrates the wide variation of buccal quality in epigenetic studies and suggests a possible approach to overcome this issue.

Keywords: DNA methylation; Epigenetics; buccal epithelial cells; tissue heterogeneity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • CpG Islands
  • DNA Methylation*
  • Epigenesis, Genetic
  • Epithelial Cells / chemistry
  • Epithelial Cells / cytology
  • Female
  • Humans
  • Male
  • Mouth Mucosa / chemistry*
  • Mouth Mucosa / cytology
  • Saliva / chemistry
  • Specimen Handling / methods*

Grant support

This research was supported by the Canadian Institutes of Health Research (MOP-126054 and MOP-287680) and the Ontario Brain Institute’s Province of Ontario Brain Neurodevelopment Network (IDS 11 02). Bioinformatics analyses were supported in part by Genome Canada through Ontario Genomics; and by the Canadian Centre for Computational Genomics (C3G), part of the Genome Technology Platform (GTP) funded by Genome Canada through Genome Quebec and Ontario Genomics.