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 W. Katz; Ravi Bandaru; Haizi Zheng; Hailu Fu; Viktor A. Adalsteinsson; Manolis Kellis

doi:10.1038/s41467-024-47196-6

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 W. Katz, Ravi Bandaru, Haizi Zheng, Hailu Fu, Viktor A. Adalsteinsson^*, Manolis Kellis^*

^*Corresponding author for this work

Biochemistry and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

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.

Original language	English (US)
Article number	2790
Journal	Nature communications
Volume	15
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-47196-6
State	Published - Dec 2024

Funding

This work was supported by the computational resources from the Broad Institute of MIT and Harvard, the Biomedical Informatics (BMI) high-performance computing cluster in CCHMC, and QUEST computational cluster in Northwestern University. This work also used the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by the National Science Foundation grant number ACI-1548562. This work used the XSEDE at the Pittsburgh Supercomputing Center (PSC) through allocation MCB190124P and MCB190006P. Y.L. is supported by the Broad Next10 grant from the Broad Institute of MIT and Harvard, trustee award from Cincinnati Children’s Hospital Medical Center, the startup grant to Y.L. from Cincinnati Children’s Hospital Medical Center, Northwestern University, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, and NHGRI (R56HG012360 to Y.L.). The authors acknowledge the generous support of the Gerstner Family Foundation to V.A.A., the Wong Family Foundation and DFCI Medical Oncology grant to A.D.C.

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Liu, Y., Reed, S. C., Lo, C., Choudhury, A. D., Parsons, H. A., Stover, D. G., Ha, G., Gydush, G., Rhoades, J., Rotem, D., Freeman, S., Katz, D. W., Bandaru, R., Zheng, H., Fu, H., Adalsteinsson, V. A., & Kellis, M. (2024). FinaleMe: Predicting DNA methylation by the fragmentation patterns of plasma cell-free DNA. Nature communications, 15(1), Article 2790. https://doi.org/10.1038/s41467-024-47196-6

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title = "FinaleMe: Predicting DNA methylation by the fragmentation patterns of plasma cell-free DNA",

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.",

author = "Yaping Liu and Reed, {Sarah C.} and Christopher Lo and Choudhury, {Atish D.} and Parsons, {Heather A.} and Stover, {Daniel G.} and Gavin Ha and Gregory Gydush and Justin Rhoades and Denisse Rotem and Samuel Freeman and Katz, {David W.} and Ravi Bandaru and Haizi Zheng and Hailu Fu and Adalsteinsson, {Viktor A.} and Manolis Kellis",

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Liu, Y, Reed, SC, Lo, C, Choudhury, AD, Parsons, HA, Stover, DG, Ha, G, Gydush, G, Rhoades, J, Rotem, D, Freeman, S, Katz, DW, Bandaru, R, Zheng, H, Fu, H, Adalsteinsson, VA & Kellis, M 2024, 'FinaleMe: Predicting DNA methylation by the fragmentation patterns of plasma cell-free DNA', Nature communications, vol. 15, no. 1, 2790. https://doi.org/10.1038/s41467-024-47196-6

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

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