Patterns of Reliability: Assessing the Reproducibility and Integrity of DNA Methylation Measurement
Rightsª 2020 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
CC0 1.0 Universal
MetadataShow full item record
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.
CitationSugden K et al. Patterns of Reliability: Assessing the Reproducibility and Integrity of DNA Methylation Measurement. Patterns (N Y). 2020 May 8;1(2):100014. doi: 10.1016/j.patter.2020.100014. Epub 2020 Apr 23.
NoteThis article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.
The following license files are associated with this item: