FinaleMe: Predicting DNA methylation by the fragmentation patterns of plasma cell-free DNA.

Liu, Yaping; Reed, Sarah C; Lo, Christopher; Choudhury, Atish D; Parsons, Heather A; Stover, Daniel G; Ha, Gavin; Gydush, Gregory et al. · Nat Commun · 2024

basic_science · Level V

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Abstract

Analysis of DNA methylation in cell-free DNA reveals clinically relevant biomarkers but requires specialized protocols such as whole-genome bisulfite sequencing. Meanwhile, millions of cell-free DNA samples are being profiled by whole-genome sequencing. Here, we develop FinaleMe, a non-homogeneous Hidden Markov Model, to predict DNA methylation of cell-free DNA and, therefore, tissues-of-origin, directly from plasma whole-genome sequencing. We validate the performance with 80 pairs of deep and shallow-coverage whole-genome sequencing and whole-genome bisulfite sequencing data.

Medical subject headings