Cell free extrachromosomal circular DNA is common in human urine
Lv, W.; Pan, X.; Han, P.; Wang, Z.; Yuan, H.; Feng, W.; Wang, Q.; Qu, K.; Xu, Z.; Li, Y.; Zheng, T.; Lin, L.; Liu, C.; Liu, X.; Li, H.; Henriksen, R. H. A.; Bolund, L.; Lin, L.; Jin, X.; Yang, H.; Zhang, X.; Regenberg, B.; Luo, Y.
Show abstract
Cell free extrachromosomal circular DNA (eccDNA) is evolving as a potential biomarker in liquid biopsies for disease diagnosis. In this study, an optimized next generation sequencing-based Circle-Seq method was developed to investigate urinary cell free eccDNA (ucf-eccDNA) from 28 adult healthy volunteers (mean age = 28, 19 males/ 9 females). The genomic distributions and sequence compositions of ucf-eccDNAs were comprehensively characterized. Approximately 1.2 million unique ucf-eccDNAs are identified, covering 14.9% of the human genome. Comprehensive characterization of ucf-eccDNAs show that ucf-eccDNAs contain higher GC content than flanking genomic regions. Most eccDNAs are less than 1000 bp and present four pronounced peaks at 203, 361, 550 and 728 bp, indicating the association between eccDNAs and the numbers of intact nucleosomes. Analysis of genomic distribution of ucf-eccDNAs show that eccDNAs are found in all chromosomes but enriched in chromosomes i.e. chr.17, 19 and 20 with high density of protein-codding genes, CpG islands, SINE and simple repeat elements. Lastly, analysis of sequence motif signatures at eccDNA junction sites reveal that direct repeats (DRs) are commonly found, indicating a potential role of DRs in eccDNA biogenesis. This work underscores the deep sequencing analysis of ucf-eccDNAs and provides a valuable reference resource for exploring potential applications of ucf-eccDNA as diagnostic biomarkers of urogenital disorders in the future. Significance StatementExtrachromosomal circular DNA (eccDNA) is an important genetic element and a biomarker for disease diagnosis and treatment. In this study, we conduct a comprehensive characterization of urinary cell free eccDNA (ucf-eccDNA) in 28 heathy subjects. Over one million ucf-eccDNAs are identified. Ucf-eccDNAs are characterized as high GC content. The size of most ucf-eccDNAs is less than 1000 bp and enriched in four peaks resembling the size of single, double, triple, and quadruple nucleosomes. The genomic distribution of ucf-eccDNAs is enriched in generic regions, protein-coding genes, Alu, CpG islands, SINE and simple repeats. Sequence motif analysis of ucf-eccDNA junctions identified simple direct repeats (DRs) commonly presented in most eccDNAs, suggesting potential roles of DRs in eccDNA biogenesis.
Matching journals
The top 11 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Whole-miRNome sequencing (WMS) - a panel for targeted sequencing of all human miRNA genes 93%
- Exome-wide benchmark of difficult-to-sequence regions using short-read next-generation DNA sequencing 92%
- Genetic variations in G-Quadruplex forming sequences affect the transcription of human disease-related genes 91%
Similar papers in this journal
- Finding new cancer epigenetic and genetic biomarkers from cell-free DNA by combining SALP-seq and machine learning：esophageal cancer as an example 92%
- LBFextract: unveiling transcription factor dynamics from liquid biopsy data 91%
- RNA-seq derived sequence variations are excellent features for cell line identification 91%
Similar papers in this journal
- Impact of Salivary and Pancreatic Amylase Gene Copy Numbers on Diabetes, Obesity, and Functional Profiles of Microbiome in Northern Japanese Population 93%
- An integrated Asian human SNV and indel benchmark combining multiple sequencing methods 93%
- Genomic alterations and abnormal expression of APE2 in multiple cancers 92%
Similar papers in this journal
- Copy number variation profile-based genomic subtyping of premenstrual dysphoric disorder in Chinese 93%
- Hybrid capture-based sequencing enables unbiased recovery of SAR-CoV-2 genomes from fecal samples and characterization of the dynamics of intra-host variants 91%
- Improved in situ sequencing for high-resolution targeted spatial transcriptomic analysis in tissue sections 90%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.