Decoding coupled epigenetic-fragmentomic signals in circulating cell-free DNA for interpretable cancer diagnosis

Background

Plasma cell-free DNA (cfDNA) whole-genome methylation sequencing enables simultaneous characterization of DNA methylation and fragmentomic features for cancer detection. However, it remains unclear whether methylation library preparation faithfully preserves fragmentomic signals, how methylation and fragmentation are biologically coupled, and how these two modalities can be systematically integrated.