Priority Research Paper Volume 15, Issue 17 pp 8552—8575

Fail-tests of DNA methylation clocks, and development of a noise barometer for measuring epigenetic pressure of aging and disease

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Figure 1. Basic principles of the 1st and next gen DNAme EN clocks. (A) A schematic of the fundamental processing of DNAme arrays data into relative beta values and using these as input for the 1st gen and next gen EN DNAme clocks. A large data set with some underlying pattern suffices for forming the least erroneous linear correlation with a measured parameter. (B, C) Comparison between the epigenetic analysis of gene expression in typical biological studies (B) and the cytosines picked by EN DNAme clocks (C). (D, E) comparison between typical biomedical studies that yield significant differences between cohorts in select parameters (D) and EN DNAme clock predictions (E). Of note, high throughput sequencing is broadly available, yet clock models are typically built from less-accurate DNA hybridization data, and parallel bisulfite sequencing controls are lacking for the putative changes in DNAme of the individuals who are predicted by the clocks to be biologically older or younger.