Improved circulating tumor DNA profiling by simultaneous extraction of DNA methylation and copy number information from methylated DNA sequencing data.

ABSTRACT: Cell-free DNA (cfDNA) analysis offers a powerful, minimally invasive approach to improve cancer care by measuring tumor-specific genomic and epigenetic alterations. Here, we demonstrate the versatility of MeD-seq, a methylation-dependent sequencing assay, for comprehensive cfDNA analysis, including DNA methylation profiling, chromosomal copy number (CN) alterations, and tumor fraction (TF) estimation. MeD-seq-derived CN profiles and TF estimates from 38 colorectal cancer patients with liver metastases (CRLM) and 5 ovarian cancer patients were highly comparable to shallow whole-genome sequencing (sWGS), validating our approach. For 120 CRLM patients, we used MeD-seq CN and TF information in an improved differential methylation model, which detected additional significantly Differentially Me

SUBMITTER: Hazelaar DM 

PROVIDER: S-EPMC12816743 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature