Patterns of Reliability: Assessing the Reproducibility and Integrity of DNA Methylation Measurement.

Patterns
Karen SugdenAvshalom Caspi

Abstract

DNA methylation plays an important role in both normal human development and risk of disease. The most utilized method of assessing DNA methylation uses BeadChips, generating an epigenome-wide "snapshot" of >450,000 observations (probe measurements) per assay. However, the reliability of each of these measurements is not equal, and little consideration is paid to consequences for research. We correlated repeat measurements of the same DNA samples using the Illumina HumanMethylation450K and the Infinium MethylationEPIC BeadChips in 350 blood DNA samples. Probes that were reliably measured were more heritable and showed consistent associations with environmental exposures, gene expression, and greater cross-tissue concordance. Unreliable probes were less replicable and generated an unknown volume of false negatives. This serves as a lesson for working with DNA methylation data, but the lessons are equally applicable to working with other data: as we advance toward generating increasingly greater volumes of data, failure to document reliability risks harming reproducibility.

Citations

Nov 21, 2020·PLoS Genetics·Alejandro Martin-TrujilloAndrew J Sharp
Dec 30, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Radhika KandaswamyChloe C Y Wong
Apr 20, 2021·Frontiers in Psychiatry·Anna Starnawska, Ditte Demontis
Jul 20, 2021·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·Whitney L DoK M Venkat Narayan

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Methods Mentioned

BETA
blood draw
chip
blood drawn

Software Mentioned

GSEA
fgsea Bioconductor
affy Bioconductor
OpenMx R
R
Bioconductor

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