REMODEL: A modular framework for longitudinal ctDNA methylation profiling reveals treatment response and relapse-associated epigenetic remodeling
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ABSTRACT: Circulating tumour DNA (ctDNA) methylation profiling is a promising non-invasive tool for disease monitoring, but longitudinal interpretation is limited by variable sequencing coverage and the loss of clinically relevant signals. We developed REMODEL (Recovery-based Epigenetic Monitoring of Dynamic methylation for Longitudinal analysis), an integrated framework combining coverage-aware binning, count-based longitudinal statistics, and a novel Epigenetic Recovery Score (ERS) to quantify post-treatment methylation recovery. Applied to 17 serial plasma samples from two T-cell lymphoma patients (2,025 genomic bins), REMODEL distinguished durable remission, characterized by coordinated demethylation (86.4% of bins) and sustained positive ERS, from relapse, marked by widespread hypermethylation (64.9% of bins) and persistently negative ERS despite clinical remission. By integrating dynamic methylation detection with recovery modelling, REMODEL provides an interpretable framework for longitudinal ctDNA methylation analysis and minimal residual disease monitoring.
ORGANISM(S): Homo sapiens
PROVIDER: GSE342177 | GEO | 2026/08/06
REPOSITORIES: GEO
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