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

Lookup NU author(s): Misti McCainORCiD, Professor Derek Mann, Professor Helen Reeves

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

AbstractINTRODUCTIONRESULTSDISCUSSIONMATERIALS AND METHODSAcknowledgmentsSupplementary MaterialsREFERENCES AND NOTES0eLettersAbstractMultimodal, 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 metadata

Author(s): SiejkaZielinska P, Cheng J, Jackson F, Liu Y, Soonawalla Z, Reddy S, Silva M, Puta L, McCain MV, Culver E, Bekkali N, SchusterBockler B, Palamara PF, Mann D, Reeves H, Barnes E, Sivakumar S, Song C

Publication type: Article

Publication status: Published

Journal: Science Advances

Year: 2021

Volume: 7

Issue: 36

Online publication date: 01/09/2021

Acceptance date: 01/09/2021

Date deposited: 17/11/2021

ISSN (electronic): 2375-2548

Publisher: American Association for the Advancement of Science (AAAS)

URL: https://doi.org/10.1126/sciadv.abh0534

DOI: 10.1126/sciadv.abh0534


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Funding

Funder referenceFunder name
C2195/A27450
C30358/A29725
C9380/A26813
C18342/A23390Cancer Research UK CRUK (open competition)
C63763/A26394
C63763/A27122
Ludwig Institute for Cancer Research
the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC)

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