FinaleMe: Predicting DNA methylation by the fragmentation patterns of plasma cell-free DNA
Yaping Liu, Sarah C. Reed, Christopher Lo, Atish D. Choudhury, Heather A. Parsons, Daniel G. Stover, Gavin Ha, Gregory Gydush, Justin Rhoades, Denisse Rotem, Samuel S. Freeman, David Katz, Ravi Bandaru, Haizi Zheng, Hailu Fu, Viktor A. Adalsteinsson, Manolis Kellis
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.