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Cell-free DNA TAPS provides multimodal information for early cancer detection

Abstract:
Multimodal, genome-wide characterization of epigenetic and genetic information in circulating cell-free DNA (cfDNA) could enable more sensitive early cancer detection, but it is technologically challenging. Recently, we developed TET-assisted pyridine borane sequencing (TAPS), which is a mild, bisulfite-free method for base-resolution direct DNA methylation sequencing. Here, we optimized TAPS for cfDNA (cfTAPS) to provide high-quality and high-depth whole-genome cell-free methylomes. We applied cfTAPS to 85 cfDNA samples from patients with hepatocellular carcinoma (HCC) or pancreatic ductal adenocarcinoma (PDAC) and noncancer controls. From only 10 ng of cfDNA (1 to 3 ml of plasma), we generated the most comprehensive cfDNA methylome to date. We demonstrated that cfTAPS provides multimodal information about cfDNA characteristics, including DNA methylation, tissue of origin, and DNA fragmentation. Integrated analysis of these epigenetic and genetic features enables accurate identification of early HCC and PDAC.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1126/sciadv.abh0534

Authors

More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Oxford Ludwig Institute
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Target Discovery Institute
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
NDM
Sub department:
Oxford Ludwig Institute
Role:
Author


Publisher:
American Association for the Advancement of Science
Journal:
Science Advances More from this journal
Volume:
7
Issue:
36
Article number:
eabh0534
Publication date:
2021-09-01
Acceptance date:
2021-07-14
DOI:
EISSN:
2375-2548


Language:
English
Keywords:
Pubs id:
1186259
Local pid:
pubs:1186259
Deposit date:
2021-07-14
ARK identifier:

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