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.

DNA methylation from cell-free DNA (cfDNA) can be profiled using whole genome bisulfite sequencing (WGBS). Here, the authors develop a computational method, FinaleMe, that predicts DNA methylation and tissues of-origin in cfDNA and validate its performance using paired deep and shallow-coverage whole-genome sequencing (WGS) and WGBS data.

Details

Title
FinaleMe: Predicting DNA methylation by the fragmentation patterns of plasma cell-free DNA
Author
Liu, Yaping 1   VIAFID ORCID Logo  ; Reed, Sarah C. 2 ; Lo, Christopher 3 ; Choudhury, Atish D. 4   VIAFID ORCID Logo  ; Parsons, Heather A. 5   VIAFID ORCID Logo  ; Stover, Daniel G. 5   VIAFID ORCID Logo  ; Ha, Gavin 3   VIAFID ORCID Logo  ; Gydush, Gregory 3 ; Rhoades, Justin 3 ; Rotem, Denisse 3 ; Freeman, Samuel 3   VIAFID ORCID Logo  ; Katz, David W. 6   VIAFID ORCID Logo  ; Bandaru, Ravi 6   VIAFID ORCID Logo  ; Zheng, Haizi 7   VIAFID ORCID Logo  ; Fu, Hailu 6   VIAFID ORCID Logo  ; Adalsteinsson, Viktor A. 3   VIAFID ORCID Logo  ; Kellis, Manolis 8   VIAFID ORCID Logo 

1  Northwestern University, Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Chicago, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, USA (GRID:grid.16753.36) (ISNI:0000 0004 0619 6876); Cincinnati Children’s Hospital Medical Center, Division of Human Genetics, Cincinnati, USA (GRID:grid.239573.9) (ISNI:0000 0000 9025 8099); Cincinnati Children’s Hospital Medical Center, Division of Biomedical Informatics, Cincinnati, USA (GRID:grid.239573.9) (ISNI:0000 0000 9025 8099); University of Cincinnati College of Medicine, Department of Pediatrics, Cincinnati, USA (GRID:grid.24827.3b) (ISNI:0000 0001 2179 9593); University of Cincinnati Center for Environmental Genetics, Cincinnati, USA (GRID:grid.24827.3b) (ISNI:0000 0001 2179 9593); University of Cincinnati Cancer Center, Cincinnati, USA (GRID:grid.24827.3b) (ISNI:0000 0001 2179 9593); Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34) (ISNI:0000 0004 0546 1623); Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, USA (GRID:grid.116068.8) (ISNI:0000 0001 2341 2786) 
2  Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34) (ISNI:0000 0004 0546 1623); Vanderbilt University School of Medicine, Medical Scientist Training Program, Nashville, USA (GRID:grid.152326.1) (ISNI:0000 0001 2264 7217) 
3  Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34) (ISNI:0000 0004 0546 1623) 
4  Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34) (ISNI:0000 0004 0546 1623); Dana-Farber Cancer Institute, Boston, USA (GRID:grid.65499.37) (ISNI:0000 0001 2106 9910) 
5  Dana-Farber Cancer Institute, Boston, USA (GRID:grid.65499.37) (ISNI:0000 0001 2106 9910) 
6  Northwestern University, Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Chicago, USA (GRID:grid.16753.36) (ISNI:0000 0001 2299 3507); Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, USA (GRID:grid.16753.36) (ISNI:0000 0004 0619 6876); Cincinnati Children’s Hospital Medical Center, Division of Human Genetics, Cincinnati, USA (GRID:grid.239573.9) (ISNI:0000 0000 9025 8099) 
7  Cincinnati Children’s Hospital Medical Center, Division of Human Genetics, Cincinnati, USA (GRID:grid.239573.9) (ISNI:0000 0000 9025 8099) 
8  Broad Institute of MIT and Harvard, Cambridge, USA (GRID:grid.66859.34) (ISNI:0000 0004 0546 1623); Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, USA (GRID:grid.116068.8) (ISNI:0000 0001 2341 2786) 
Pages
2790
Publication year
2024
Publication date
2024
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-024-47196-6
ProQuest document ID
3020236060
Copyright
© The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.