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 Freeman; David Katz; Ravi Bandaru; Haizi Zheng; Hailu Fu; Viktor A Adalsteinsson; Manolis Kellis

doi:10.1101/2024.01.02.573710

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

bioRxiv [Preprint]. 2024 Jan 2:2024.01.02.573710. doi: 10.1101/2024.01.02.573710.

Authors

Yaping Liu^{1

2

3

4

5

6

7

8

9}, Sarah C Reed⁸, Christopher Lo⁸, Atish D Choudhury^{8

10}, Heather A Parsons¹⁰, Daniel G Stover¹⁰, Gavin Ha⁸, Gregory Gydush⁸, Justin Rhoades⁸, Denisse Rotem⁸, Samuel Freeman⁸, David Katz^{1

2

3}, Ravi Bandaru^{1

2

3}, Haizi Zheng³, Hailu Fu^{1

2

3}, Viktor A Adalsteinsson⁶, Manolis Kellis^{6

7}

Affiliations

¹ Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
² Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL 60611.
³ Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
⁴ Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229.
⁵ Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH 45229.
⁶ University of Cincinnati Center for Environmental Genetics, Cincinnati, OH 45229.
⁷ University of Cincinnati Cancer Center, Cincinnati, OH 45229.
⁸ Broad Institute of MIT and Harvard, Cambridge, MA 02142.
⁹ Massachusetts Institute of Technology, Computer Science and Artificial Intelligence Laboratory, Cambridge, MA 02139.
¹⁰ Dana-Farber Cancer Institute, Boston, MA, USA.

Abstract

Analysis of DNA methylation in cell-free DNA (cfDNA) reveals clinically relevant biomarkers but requires specialized protocols and sufficient input material that limits its applicability. Millions of cfDNA samples have been profiled by genomic sequencing. To maximize the gene regulation information from the existing dataset, we developed FinaleMe, a non-homogeneous Hidden Markov Model (HMM), to predict DNA methylation of cfDNA and, therefore, tissues-of-origin directly from plasma whole-genome sequencing (WGS). We validated the performance with 80 pairs of deep and shallow-coverage WGS and whole-genome bisulfite sequencing (WGBS) data.

Keywords: Cell-free DNA; DNA methylation; fragmentation; tissues-of-origin; whole-genome sequencing.

Publication types

Preprint

Grants and funding

R56 HG012360/HG/NHGRI NIH HHS/United States