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

ABSTRACT: This study shows that Elastic Net (EN) DNA methylation (DNAme) clocks have low accuracy of predictions for individuals of the same age and a low resolution between healthy and disease cohorts; caveats inherent in applying linear model to non-linear processes. We found that change in methylation of cytosines with age is, interestingly, not the determinant for their selection into the clocks. Moreover, an EN clock's selected cytosines change when non-clock cytosines are removed from the training data; as expected from optimization in a machine learning (ML) context, but inconsistently with the identification of health markers in a biological context. To address these limitations, we moved from predictions to measurement of biological age, focusing on the cytosines that on average remain inva

SUBMITTER: Mei X 

PROVIDER: S-EPMC10522373 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature