DNA methylation quality control decisions, removed beta values, and their influence on epigenetic clocks

Area of Science:

• Genomics
• Epigenetics
• Computational Biology

Background:

• Epigenetic clocks, based on DNA methylation, are vital tools in biological aging research.
• Quality control (QC) processes generate removed beta values that require careful handling in clock construction.

Purpose of the Study:

• To assess the impact of different QC thresholds on DNA methylation data.
• To evaluate various imputation methods for removed beta values and their effect on epigenetic clock accuracy.

Main Methods:

• Applied detection p-value and bead count thresholds during DNA methylation data QC.
• Characterized the distribution of removed beta values.
• Tested mean, median, KNN, and methyLImp imputation methods for removed beta values.

Main Results:

• QC thresholds significantly alter the distribution of beta values.
• Most imputation methods showed no consistent bias in epigenetic clocks.
• Imputing 0 for removed values (CpG exclusion) introduced significant proportional bias.

Conclusions:

• Recommends imputation of removed beta values for constructing epigenetic clocks.
• Avoids excluding CpGs on a per-sample basis to maintain clock accuracy.