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 6. The fundamental paradigm of noise barometer; DNAme clocks do not rely on DNAme noise. (A) Shown are polynomial fit curves of the chronological age v. sums of 460-, 293-, 5 SDs, SD and the dot plot line-fit of a single cytosine from the most regulated in young group, and the sums of 143, 448 SDs of all heteroscedastic cytosines with 20% or larger SD in old than young; the unfiltered 450K summed SDs are the black dot scatter that is overlaid with the 143, 448 (143K) line graph. These data are on the six combined datasets of patients with various diseases (red lines) and their healthy controls (blue lines). All noise detectors, but not the unfiltered 450K DNAme cytosines, outline a similar progression of biological aging of the healthy subjects, clearly distinguishing it from the disease-influenced changes. Each dot is the age range. (B) Dashed blue line shows the Median of summed SDs of three DNAme array healthy controls datasets that have the most samples (Arthritis, MS, and PD); this Median line is overlayed with the dot plots of each of these individual datasets, color-coded. Each dot is the age range. (C) Venn Diagrams show the presence of the 143K cytosines in the 50 and 460 noise barometers and in the DNAme EN clocks, color-coding is the same, as in Figure 5. (D) Scatter plots of the coefficient of variation of the cytosines’ SD regressed on age are plotted against their rank/EN weights for the published 1st generation clock, PhenoAge and PACE, [15].