Molecular characterization of cell-free eccDNAs in human plasma

Abstract Extrachromosomal circular DNAs (eccDNAs) have been reported in most eukaryotes. However, little is known about the cell-free eccDNA profiles in circulating system such as blood. To characterize plasma cell-free eccDNAs, we performed sequencing analysis in 26 libraries from three blood donor...

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Autores principales:	Jing Zhu, Fan Zhang, Meijun Du, Peng Zhang, Songbin Fu, Liang Wang
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f225f617c66e4c15b3de2466f9baf9f4
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spelling	oai:doaj.org-article:f225f617c66e4c15b3de2466f9baf9f42021-12-02T15:06:26ZMolecular characterization of cell-free eccDNAs in human plasma10.1038/s41598-017-11368-w2045-2322https://doaj.org/article/f225f617c66e4c15b3de2466f9baf9f42017-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-11368-whttps://doaj.org/toc/2045-2322Abstract Extrachromosomal circular DNAs (eccDNAs) have been reported in most eukaryotes. However, little is known about the cell-free eccDNA profiles in circulating system such as blood. To characterize plasma cell-free eccDNAs, we performed sequencing analysis in 26 libraries from three blood donors and negative controls. We identified thousands of unique plasma eccDNAs in the three subjects. We observed proportional eccDNA increase with initial DNA input. The detected eccDNAs were also associated with circular DNA enrichment efficiency. Increasing the sequencing depth in an additional sample identified many more eccDNAs with highly heterogenous molecular structure. Size distribution of eccDNAs varied significantly from 31 bp to 19,989 bp. We found significantly higher GC content in smaller eccDNAs (<500 bp) than the larger ones (>500 bp) (p < 0.01). We also found an enrichment of eccDNAs at exons and 3′UTR (enrichment folds from 1.36 to 3.1) as well as the DNase hypersensitive sites (1.58–2.42 fold), H3K4Me1 (1.23–1.42 fold) and H3K27Ac (1.33–1.62 fold) marks. Junction sequence analysis suggested fundamental role of nonhomologous end joining mechanism during eccDNA formation. Further characterization of the extracellular eccDNAs in peripheral blood will facilitate understanding of their molecular mechanisms and potential clinical utilities.Jing ZhuFan ZhangMeijun DuPeng ZhangSongbin FuLiang WangNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jing Zhu Fan Zhang Meijun Du Peng Zhang Songbin Fu Liang Wang Molecular characterization of cell-free eccDNAs in human plasma
description	Abstract Extrachromosomal circular DNAs (eccDNAs) have been reported in most eukaryotes. However, little is known about the cell-free eccDNA profiles in circulating system such as blood. To characterize plasma cell-free eccDNAs, we performed sequencing analysis in 26 libraries from three blood donors and negative controls. We identified thousands of unique plasma eccDNAs in the three subjects. We observed proportional eccDNA increase with initial DNA input. The detected eccDNAs were also associated with circular DNA enrichment efficiency. Increasing the sequencing depth in an additional sample identified many more eccDNAs with highly heterogenous molecular structure. Size distribution of eccDNAs varied significantly from 31 bp to 19,989 bp. We found significantly higher GC content in smaller eccDNAs (<500 bp) than the larger ones (>500 bp) (p < 0.01). We also found an enrichment of eccDNAs at exons and 3′UTR (enrichment folds from 1.36 to 3.1) as well as the DNase hypersensitive sites (1.58–2.42 fold), H3K4Me1 (1.23–1.42 fold) and H3K27Ac (1.33–1.62 fold) marks. Junction sequence analysis suggested fundamental role of nonhomologous end joining mechanism during eccDNA formation. Further characterization of the extracellular eccDNAs in peripheral blood will facilitate understanding of their molecular mechanisms and potential clinical utilities.
format	article
author	Jing Zhu Fan Zhang Meijun Du Peng Zhang Songbin Fu Liang Wang
author_facet	Jing Zhu Fan Zhang Meijun Du Peng Zhang Songbin Fu Liang Wang
author_sort	Jing Zhu
title	Molecular characterization of cell-free eccDNAs in human plasma
title_short	Molecular characterization of cell-free eccDNAs in human plasma
title_full	Molecular characterization of cell-free eccDNAs in human plasma
title_fullStr	Molecular characterization of cell-free eccDNAs in human plasma
title_full_unstemmed	Molecular characterization of cell-free eccDNAs in human plasma
title_sort	molecular characterization of cell-free eccdnas in human plasma
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f225f617c66e4c15b3de2466f9baf9f4
work_keys_str_mv	AT jingzhu molecularcharacterizationofcellfreeeccdnasinhumanplasma AT fanzhang molecularcharacterizationofcellfreeeccdnasinhumanplasma AT meijundu molecularcharacterizationofcellfreeeccdnasinhumanplasma AT pengzhang molecularcharacterizationofcellfreeeccdnasinhumanplasma AT songbinfu molecularcharacterizationofcellfreeeccdnasinhumanplasma AT liangwang molecularcharacterizationofcellfreeeccdnasinhumanplasma
_version_	1718388488963883008

Molecular characterization of cell-free eccDNAs in human plasma

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