A chromatin fiber model explains cell-free DNA fragmentation signatures of active regulatory elements.

ABSTRACT: Circulating cell-free DNA (cfDNA) assays are being widely adopted in oncology and maternal-fetal medicine. Patterns of cfDNA fragmentation can provide useful information about gene regulation and expression in human disease from a blood draw. Here, we demonstrate that enhancer RNA expression - a marker of enhancer activity - can be inferred from local patterns of cfDNA fragmentation. We define a transcriptional activation score (TAS) that predicts expression of enhancers and genes based on cfDNA fragment sizes and positions near transcriptional start sites (TSSs). The TAS identifies activity of cancer-associated enhancers in patients with cancer, distinguishes clinically relevant cancer subtypes, and identifies activation of enhancers associated with treatment resistance and therapy respon

SUBMITTER: Yang A 

PROVIDER: S-EPMC12637484 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature