Read-level DNA methylation deconvolution enhances circulating tumor DNA detection.

ABSTRACT: DNA methylation is a key epigenetic modification underlying cellular identity. Conventional methods based on CpG site-level data often lack sensitivity in detecting low-frequency methylation signals. Here, we present Alpha, a novel method combining unbiased segmentation with robust read-level identification of low frequency cell-type-specific methylation signals. Methylation markers identified by Alpha exhibited significant enrichment in regulatory genomic elements such as enhancers, active promoters, and transcription factor binding sites. In simulated cell-type admixtures, Alpha-derived markers demonstrated improved deconvolution performance, exhibiting lower error metrics compared to beta-value based methods (DSS), even with limited marker numbers (N < 50). We combined Alpha with a non-

SUBMITTER: Qi T 

PROVIDER: S-EPMC12536878 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature