Patterns of Reliability: Assessing the Reproducibility and Integrity of DNA Methylation Measurement
Patterns of Reliability: Assessing the Reproducibility and Integrity of DNA Methylation Measurement
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DOI：
10.1016/j.patter.2020.100014
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发表时间：
2020-05-08
期刊：
影响因子：
6.5
通讯作者：
Caspi, Avshalom
中科院分区：
文献类型：
--
作者：
Sugden, Karen;Hannon, Eilis J.;Caspi, Avshalom
DNA甲基化在人类正常发育和疾病风险中都起着重要作用。最常用的DNA甲基化评估方法使用BeadChips，每次检测生成一个表观基因组范围的450,000个观察(探针测量)的“快照”。然而，这些测量的可靠性并不相等，很少考虑研究的结果。我们使用Illumina Human Megylation450K和Infinium甲基化-EPIC BeadChips对350个血液DNA样本进行了重复测量。可靠测量的探针更易遗传，并与环境暴露、基因表达和更大的跨组织一致性显示出一致的相关性。不可靠的探针更不容易复制，并产生未知数量的假阴性。这是处理DNA甲基化数据的一个教训，但这些教训同样适用于处理其他数据：随着我们朝着生成越来越多的数据量迈进，未能记录可靠性有可能损害重复性。
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 Methylation-EPIC 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.