Eighth Affiliated Hospital of Sun Yat-sen University

Plasma cell-free DNA methylation sequencing, long used only to read methylation, is shown to partially retain fragmentomic signals such as fragment length and end motifs. The study delineates co-methylated blocks directly in plasma cfDNA, places methylation and fragmentomic features in the same genomic intervals, and builds an interpretable ensemble model for cancer detection and tissue-of-origin prediction. Cross-platform comparisons show major fragmentomic patterns are recapitulated in methylation sequencing, though preservation varies by feature.

Plasma cell-free DNA methylation sequencing, long used only to read methylation, is shown to partially retain fragmentomic signals such as fragment length and end motifs. The study delineates co-methylated blocks directly in plasma cfDNA, places methylation and fragmentomic features in the same genomic intervals, and builds an interpretable ensemble model for cancer detection and tissue-of-origin prediction. Cross-platform comparisons show major fragmentomic patterns are recapitulated in methylation sequencing, though preservation varies by feature.