The characteristics of extrachromosomal circular DNA in patients with end-stage renal disease

Abstract

Background End-stage renal disease (ESRD) is the final stage of chronic kidney disease (CKD). In addition to the structurally intact chromosome genomic DNA, there is a double-stranded circular DNA called extrachromosomal circular DNA (eccDNA), which is thought to be involved in the epigenetic regulation of human disease. However, the features of eccDNA in ESRD patients are barely known. In this study, we identified eccDNA from ESRD patients and healthy people, as well as revealed the characteristics of eccDNA in patients with ESRD. Methods Using the high-throughput Circle-Sequencing technique, we examined the eccDNA in peripheral blood mononuclear cells (PBMCs) from healthy people (NC) (n = 12) and ESRD patients (n = 16). We analyzed the length distribution, genome elements, and motifs feature of eccDNA in ESRD patients. Then, after identifying the specific eccDNA in ESRD patients, we explored the potential functions of the target genes of the specific eccDNA. Finally, we investigated the probable hub eccDNA using algorithms. Results In total, 14,431 and 11,324 eccDNAs were found in the ESRD and NC groups, respectively, with sizes ranging from 0.01 kb to 60 kb at most. Additionally, the ESRD group had a greater distribution of eccDNA on chromosomes 4, 11, 13, and 20. In two groups, we also discovered several motifs of specific eccDNAs. Furthermore, we identified 13,715 specific eccDNAs in the ESRD group and 10,585 specific eccDNAs in the NC group, both of which were largely annotated as mRNA catalog. Pathway studies using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that the specific eccDNA in ESRD was markedly enriched in cell junction and communication pathways. Furthermore, we identified potentially 20 hub eccDNA-targeting genes from all ESRD-specific eccDNA-targeting genes. Also, we found that 39 eccDNA-targeting genes were associated with ESRD, and some of these eccDNAs may be related to the pathogenesis of ESRD. Conclusions Our findings revealed the characteristics of eccDNA in ESRD patients and discovered potentially hub and ESRD-relevant eccDNA-targeting genes, suggesting a novel probable mechanism of ESRD.

Identification and characterization of extrachromosomal circular DNA in large‐artery atherosclerotic stroke

“…Compared with the healthy controls (CON), the size distribution and genomic characteristics of plasma eccDNA were not significantly altered in the LAA stroke patients. Similar with previous researches on plasma and cells/tissues from patients and healthy controls, 17 , 18 , 19 the formation of eccDNAs was positively related to the distribution of genes on the chromosomes both in the CON and LAA stroke patients. The size of more than 90% eccDNAs was <1 kb, and two peaks were observed within 1 kb in the CON and LAA stroke patients.…”

A comprehensive analysis of library preparation methods shows high heterogeneity of extrachromosomal circular DNA but distinct chromosomal amount levels reflecting different cell states

“…S1 and S5†), which may serve as an important feature for eccDNA. Expanding upon previous research that focused solely on specific overlapped rings between different samples, 8,9,44 we exploited this global feature as an eccDNA signature. Additionally, samples with the same treatment condition tended to cluster together based on the distribution of eccDNA across genomic elements.…”

Exploring the Role of Clustered Mutations in Carcinogenesis and Their Potential Clinical Implications in Cancer

“…Additionally, 76.1% of kataegic occurrences display mutational signatures linked to AID/APOBEC3 deaminase activity [ 1 ]. Recently, extrachromosomal DNA (ecDNA)-associated kataegis , termed kyklonas (Greek for cyclone), was found in 31% of samples with circular ecDNA and highly open chromatin, facilitating interactions across vast genomic distances [ 33 , 34 ]. In ecDNA regions containing cancer-related genes, there is a pronounced increase in kyklonic episodes and the associated mutational load compared to ecDNA segments devoid of such genes.…”