Patterns of Reliability: Assessing the Reproducibility and Integrity of DNA Methylation Measurement.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32885222.
- Also identified by DOI 10.1016/j.patter.2020.100014 and PMC identifier 7467214.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.