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Detection and characterization of jagged ends of double-stranded DNA in plasma
Cell-free DNA in plasma has been used for noninvasive prenatal testing and cancer liquid biopsy. The physical properties of cell-free DNA fragments in plasma, such as fragment sizes and ends, have attracted much recent interest, leading to the emerging field of cell-free DNA fragmentomics. However,...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462074/ https://www.ncbi.nlm.nih.gov/pubmed/32801148 http://dx.doi.org/10.1101/gr.261396.120 |
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author | Jiang, Peiyong Xie, Tingting Ding, Spencer C. Zhou, Ze Cheng, Suk Hang Chan, Rebecca W.Y. Lee, Wing-Shan Peng, Wenlei Wong, John Wong, Vincent W.S. Chan, Henry L.Y. Chan, Stephen L. Poon, Liona C.Y. Leung, Tak Y. Chan, K.C. Allen Chiu, Rossa W.K. Lo, Y.M. Dennis |
author_facet | Jiang, Peiyong Xie, Tingting Ding, Spencer C. Zhou, Ze Cheng, Suk Hang Chan, Rebecca W.Y. Lee, Wing-Shan Peng, Wenlei Wong, John Wong, Vincent W.S. Chan, Henry L.Y. Chan, Stephen L. Poon, Liona C.Y. Leung, Tak Y. Chan, K.C. Allen Chiu, Rossa W.K. Lo, Y.M. Dennis |
author_sort | Jiang, Peiyong |
collection | PubMed |
description | Cell-free DNA in plasma has been used for noninvasive prenatal testing and cancer liquid biopsy. The physical properties of cell-free DNA fragments in plasma, such as fragment sizes and ends, have attracted much recent interest, leading to the emerging field of cell-free DNA fragmentomics. However, one aspect of plasma DNA fragmentomics as to whether double-stranded plasma molecules might carry single-stranded ends, termed a jagged end in this study, remains underexplored. We have developed two approaches for investigating the presence of jagged ends in a plasma DNA pool. These approaches utilized DNA end repair to introduce differential methylation signals between the original sequence and the jagged ends, depending on whether unmethylated or methylated cytosines were used in the DNA end-repair procedure. The majority of plasma DNA molecules (87.8%) were found to bear jagged ends. The jaggedness varied according to plasma DNA fragment sizes and appeared to be in association with nucleosomal patterns. In the plasma of pregnant women, the jaggedness of fetal DNA molecules was higher than that of the maternal counterparts. The jaggedness of plasma DNA correlated with the fetal DNA fraction. Similarly, in the plasma of cancer patients, tumor-derived DNA molecules in patients with hepatocellular carcinoma showed an elevated jaggedness compared with nontumoral DNA. In mouse models, knocking out of the Dnase1 gene reduced jaggedness, whereas knocking out of the Dnase1l3 gene enhanced jaggedness. Hence, plasma DNA jagged ends represent an intrinsic property of plasma DNA and provide a link between nuclease activities and the fragmentation of plasma DNA. |
format | Online Article Text |
id | pubmed-7462074 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-74620742020-09-11 Detection and characterization of jagged ends of double-stranded DNA in plasma Jiang, Peiyong Xie, Tingting Ding, Spencer C. Zhou, Ze Cheng, Suk Hang Chan, Rebecca W.Y. Lee, Wing-Shan Peng, Wenlei Wong, John Wong, Vincent W.S. Chan, Henry L.Y. Chan, Stephen L. Poon, Liona C.Y. Leung, Tak Y. Chan, K.C. Allen Chiu, Rossa W.K. Lo, Y.M. Dennis Genome Res Method Cell-free DNA in plasma has been used for noninvasive prenatal testing and cancer liquid biopsy. The physical properties of cell-free DNA fragments in plasma, such as fragment sizes and ends, have attracted much recent interest, leading to the emerging field of cell-free DNA fragmentomics. However, one aspect of plasma DNA fragmentomics as to whether double-stranded plasma molecules might carry single-stranded ends, termed a jagged end in this study, remains underexplored. We have developed two approaches for investigating the presence of jagged ends in a plasma DNA pool. These approaches utilized DNA end repair to introduce differential methylation signals between the original sequence and the jagged ends, depending on whether unmethylated or methylated cytosines were used in the DNA end-repair procedure. The majority of plasma DNA molecules (87.8%) were found to bear jagged ends. The jaggedness varied according to plasma DNA fragment sizes and appeared to be in association with nucleosomal patterns. In the plasma of pregnant women, the jaggedness of fetal DNA molecules was higher than that of the maternal counterparts. The jaggedness of plasma DNA correlated with the fetal DNA fraction. Similarly, in the plasma of cancer patients, tumor-derived DNA molecules in patients with hepatocellular carcinoma showed an elevated jaggedness compared with nontumoral DNA. In mouse models, knocking out of the Dnase1 gene reduced jaggedness, whereas knocking out of the Dnase1l3 gene enhanced jaggedness. Hence, plasma DNA jagged ends represent an intrinsic property of plasma DNA and provide a link between nuclease activities and the fragmentation of plasma DNA. Cold Spring Harbor Laboratory Press 2020-08 /pmc/articles/PMC7462074/ /pubmed/32801148 http://dx.doi.org/10.1101/gr.261396.120 Text en © 2020 Jiang et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article, published in Genome Research, is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/. |
spellingShingle | Method Jiang, Peiyong Xie, Tingting Ding, Spencer C. Zhou, Ze Cheng, Suk Hang Chan, Rebecca W.Y. Lee, Wing-Shan Peng, Wenlei Wong, John Wong, Vincent W.S. Chan, Henry L.Y. Chan, Stephen L. Poon, Liona C.Y. Leung, Tak Y. Chan, K.C. Allen Chiu, Rossa W.K. Lo, Y.M. Dennis Detection and characterization of jagged ends of double-stranded DNA in plasma |
title | Detection and characterization of jagged ends of double-stranded DNA in plasma |
title_full | Detection and characterization of jagged ends of double-stranded DNA in plasma |
title_fullStr | Detection and characterization of jagged ends of double-stranded DNA in plasma |
title_full_unstemmed | Detection and characterization of jagged ends of double-stranded DNA in plasma |
title_short | Detection and characterization of jagged ends of double-stranded DNA in plasma |
title_sort | detection and characterization of jagged ends of double-stranded dna in plasma |
topic | Method |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7462074/ https://www.ncbi.nlm.nih.gov/pubmed/32801148 http://dx.doi.org/10.1101/gr.261396.120 |
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