Circle-Seq reveals genomic and disease-specific hallmarks in urinary cell-free extrachromosomal circular DNAs
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Circle-Seq reveals genomic and disease-specific hallmarks in urinary cell-free extrachromosomal circular DNAs. / Lv, Wei; Pan, Xiaoguang; Han, Peng; Wang, Ziyu; Feng, Weijia; Xing, Xue; Wang, Qingqing; Qu, Kunli; Zeng, Yuchen; Zhang, Cailin; Xu, Zhe; Li, Yi; Zheng, Tianyu; Lin, Ling; Liu, Chengxun; Liu, Xuemei; Li, Hanbo; Henriksen, Rasmus Amund; Bolund, Lars; Lin, Lin; Jin, Xin; Yang, Huanming; Zhang, Xiuqing; Yin, Tailang; Regenberg, Birgitte; He, Fan; Luo, Yonglun.
In: Clinical and Translational Medicine, Vol. 12, No. 4, e817, 2022.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Circle-Seq reveals genomic and disease-specific hallmarks in urinary cell-free extrachromosomal circular DNAs
AU - Lv, Wei
AU - Pan, Xiaoguang
AU - Han, Peng
AU - Wang, Ziyu
AU - Feng, Weijia
AU - Xing, Xue
AU - Wang, Qingqing
AU - Qu, Kunli
AU - Zeng, Yuchen
AU - Zhang, Cailin
AU - Xu, Zhe
AU - Li, Yi
AU - Zheng, Tianyu
AU - Lin, Ling
AU - Liu, Chengxun
AU - Liu, Xuemei
AU - Li, Hanbo
AU - Henriksen, Rasmus Amund
AU - Bolund, Lars
AU - Lin, Lin
AU - Jin, Xin
AU - Yang, Huanming
AU - Zhang, Xiuqing
AU - Yin, Tailang
AU - Regenberg, Birgitte
AU - He, Fan
AU - Luo, Yonglun
N1 - © 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.
PY - 2022
Y1 - 2022
N2 - BACKGROUND: Extrachromosomal circular deoxyribonucleic acid (eccDNA) is evolving as a valuable biomarker, while little is known about its presence in urine.METHODS: Here, we report the discovery and analysis of urinary cell-free eccDNAs (ucf-eccDNAs) in healthy controls and patients with advanced chronic kidney disease (CKD) by Circle-Seq.RESULTS: Millions of unique ucf-eccDNAs were identified and comprehensively characterised. The ucf-eccDNAs are GC-rich. Most ucf-eccDNAs are less than 1000 bp and are enriched in four pronounced peaks at 207, 358, 553 and 732 bp. Analysis of the genomic distribution of ucf-eccDNAs shows that eccDNAs are found on all chromosomes but enriched on chromosomes 17, 19 and 20 with a high density of protein-coding genes, CpG islands, short interspersed transposable elements (SINEs) and simple repeat elements. Analysis of eccDNA junction sequences further suggests that microhomology and palindromic repeats might be involved in eccDNA formation. The ucf-eccDNAs in CKD patients are significantly higher than those in healthy controls. Moreover, eccDNA with miRNA genes is highly enriched in CKD ucf-eccDNA.CONCLUSIONS: This work discovers and provides the first deep characterisation of ucf-eccDNAs and suggests ucf-eccDNA as a valuable noninnvasive biomarker for urogenital disorder diagnosis and monitoring.
AB - BACKGROUND: Extrachromosomal circular deoxyribonucleic acid (eccDNA) is evolving as a valuable biomarker, while little is known about its presence in urine.METHODS: Here, we report the discovery and analysis of urinary cell-free eccDNAs (ucf-eccDNAs) in healthy controls and patients with advanced chronic kidney disease (CKD) by Circle-Seq.RESULTS: Millions of unique ucf-eccDNAs were identified and comprehensively characterised. The ucf-eccDNAs are GC-rich. Most ucf-eccDNAs are less than 1000 bp and are enriched in four pronounced peaks at 207, 358, 553 and 732 bp. Analysis of the genomic distribution of ucf-eccDNAs shows that eccDNAs are found on all chromosomes but enriched on chromosomes 17, 19 and 20 with a high density of protein-coding genes, CpG islands, short interspersed transposable elements (SINEs) and simple repeat elements. Analysis of eccDNA junction sequences further suggests that microhomology and palindromic repeats might be involved in eccDNA formation. The ucf-eccDNAs in CKD patients are significantly higher than those in healthy controls. Moreover, eccDNA with miRNA genes is highly enriched in CKD ucf-eccDNA.CONCLUSIONS: This work discovers and provides the first deep characterisation of ucf-eccDNAs and suggests ucf-eccDNA as a valuable noninnvasive biomarker for urogenital disorder diagnosis and monitoring.
KW - Biomarkers
KW - DNA
KW - DNA, Circular/genetics
KW - Female
KW - Genomics
KW - Humans
KW - Male
KW - Renal Insufficiency, Chronic/diagnosis
U2 - 10.1002/ctm2.817
DO - 10.1002/ctm2.817
M3 - Journal article
C2 - 35474296
VL - 12
JO - Clinical and Translational Medicine
JF - Clinical and Translational Medicine
SN - 2001-1326
IS - 4
M1 - e817
ER -
ID: 307748262