Abstract
MOTIVATION: DNA methylation patterns provide precise and accurate estimates of biological age due to their robustness and predictable changes associated with aging processes. Although several methylation aging clocks have been developed in recent years, they are primarily designed for DNA methylation array data, which has limited CpG coverage and detection sensitivity compared to bisulfite sequencing data. RESULTS: Here, we present BS-clock, a novel DNA methylation clock for human aging based on bisulfite sequencing data. Using BS-seq data from 529 samples retrieved from four tissues, our BS-clock achieves higher correlations with chronological age in multiple tissue types compared to existing array-based clocks. Our study revealed age-dependent aging rates across different age stages and disease conditions, and overall low cross-tissue prediction capability by applying the model trained on one tissue type to others. In summary, BS-clock overcomes limitations of array-based techniques, offering genome-wide CpG site coverage and more robust and accurate aging quantification. This research paves the way for advanced epigenetic studies of aging and holds promise for developing targeted interventions to promote healthy aging. AVAILABILITY AND IMPLEMENTATION: All analysis codes for reproducing the results of the study are publicly available at https://github.com/hucongcong97/BS-clock.