CUE: CpG impUtation ensemble for DNA methylation levels across the human methylation450 (HM450) and EPIC (HM850) BeadChip platforms

DNA methylation at CpG dinucleotides is one of the most extensively studied epigenetic marks. With technological advancements, geneticists can profile DNA methylation with multiple reliable approaches. However, profiling platforms can differ substantially in the CpGs they assess, consequently hinder...

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Bibliographic Details
Published in:Epigenetics 2021-08, Vol.16 (8), p.851-861
Main Authors: Li, Gang, Raffield, Laura, Logue, Mark, Miller, Mark W., Santos, Hudson P., O'Shea, T. Michael, Fry, Rebecca C., Li, Yun
Format: Article
Language:English
Subjects:
CpG Islands
DNA Methylation
ensemble learning
Epigenomics
Female
High-Throughput Nucleotide Sequencing
HM450
HM850
Humans
imputation
Infant, Newborn
placenta
Pregnancy
Research Paper
whole blood
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Summary:DNA methylation at CpG dinucleotides is one of the most extensively studied epigenetic marks. With technological advancements, geneticists can profile DNA methylation with multiple reliable approaches. However, profiling platforms can differ substantially in the CpGs they assess, consequently hindering integrated analysis across platforms. Here, we present CpG impUtation Ensemble (CUE), which leverages multiple classical statistical and modern machine learning methods, to impute from the Illumina HumanMethylation450 (HM450) BeadChip to the Illumina HumanMethylationEPIC (HM850) BeadChip. Data were analysed from two population cohorts with methylation measured both by HM450 and HM850: the Extremely Low Gestational Age Newborns (ELGAN) study (n = 127, placenta) and the VA Boston Posttraumatic Stress Disorder (PTSD) genetics repository (n = 144, whole blood). Cross-validation results show that CUE achieves the lowest predicted root-mean-square error (RMSE) (0.026 in PTSD) and the highest accuracy (99.97% in PTSD) compared with five individual methods tested, including k-nearest-neighbours, logistic regression, penalized functional regression, random forest, and XGBoost. Finally, among all 339,033 HM850-only CpG sites shared between ELGAN and PTSD, CUE successfully imputed 289,604 (85.4%) sites, where success was defined as RMSE < 0.05 and accuracy >95% in PTSD. In summary, CUE is a valuable tool for imputing CpG methylation from the HM450 to HM850 platform.
ISSN:1559-2294
1559-2308
1559-2308
DOI:10.1080/15592294.2020.1827716