A statistical method that removes technical noise reduces the test-retest variation of split samples on epigenetic clocks to a maximum difference of about one year.
"we actually developed a statistical method that completely removes all this technical noise. And I won't go into the math for people on the podcast, but basically, we can get this down to: you can split the sample, and now you're getting only about one year difference at max." (said at 1:05:09)
A 2022 study by Higgins-Chen, Levine, and colleagues introduced principal-component-based (PC) epigenetic clocks to address technical noise in DNA methylation assays. In their validation across six prominent epigenetic clocks, the PC approach significantly reduced technical noise between split-sample replicates (from discrepancies of up to 9 years down to agreement for most replicates within 1.5 years). However, the claim that the method "completely removes all" technical noise and restricts differences to "at max" about one year overstates the findings, as residual variation remains and 1.5 years reflected the range for most, but not strictly all, replicates.
- partial: A computational solution for bolstering reliability of epigenetic clocks: Implications for… (Nature aging 2022)
"Here we show technical noise produces deviations up to 9 years between replicates for six prominent epigenetic clocks, limiting their utility. We present a computational solution to bolster reliability, calculating principal components from CpG-level data as input for biological age prediction. Our retrained principal-component versions of six clocks show agreement between most replicates within 1.5 years, improved detection of clock associations and intervention effects, and reliable longitudinal trajectories in vivo and in vitro ." (abstract, results, passage verified)
pubmedfull study (doi)