Characterization of Plasma Extrachromosomal Circular DNA in Gouty Arthritis

Abstract

Objective: Extrachromosomal circular DNA elements (eccDNAs) are known for their broad existence in cells and plasma, which may potentially play important roles in many biological processes. Our aim was to identify potentially functional or marked eccDNAs in gout patients.Methods: The Circle-Seq approach was applied for eccDNA detection from plasma in acute gout patients and healthy controls. Further analysis was performed on the distribution of genomic elements and eccDNA gene annotations in two groups.Results: We detected 57,216 and 109,683 eccDNAs from the acute gout and healthy control plasma, respectively. EccDNAs were mapped to the reference genome to identify diverse classes of genomic elements and there was no significant difference of eccDNAs on genomic element annotation between gout and control group. A total of 256 eccDNA-associated genes were detected as gout unique eccDNA genes, including COL1A1 and EPB42, which potentially contribute to hyperuricemia and gout, and a couple of genes involved in inflammation or immune response. Enrichment analysis showed that these eccDNA genes were highly correlated with defense response, stress response, and immune and inflammatory responses, including T cell receptor signaling pathway, Fc epsilon RI signaling pathway, and JAK-STAT signaling pathway.Conclusion: Our discovery reveals the novel potential biological roles of plasma eccDNAs in gouty arthritis.

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

“…To investigate the mechanism of eccDNA origin, the sequence pattern near the breakpoint has attracted significant research attention. 34,35 Therefore, we examined the DNA sequences flanking the start and end sites of eccDNAs within a 10 bp region to compare the nucleotide composition resulting from different protocols (Fig. 6a and S3†).…”

RAES：a rapid and high-fidelity method for artificial extrachromosomal circular DNA synthesis and its application as a bacterial DNA-free vector for robust microRNA overexpression

“…As its distinct topological structure and enigmatic functions in cells, eccDNA, the "magic" mobile and circular DNA molecule, has attracted increasing research interest in recent years. Although numerous studies suggested its potential role in various physiological and pathological statuses, including tumorigenesis [7,21,26], drug-resistance [16,34], aging [35,36], human reproduction [4,8,9] and immune-response [24,37,38], the detailed molecular role of eccDNA remains to be elucidated. One major hurdle in the area is the lack of a rapid and cost-effective method for eccDNA synthesis.…”

Extrachromosomal circular DNA: Current status and future prospects

“…For instance, by comparing sequences between the transcripts of the TTN gene and the associated eccDNA sequences, they proved that its production resulted from TTN circle and demonstrated that a fraction of eccDNAs residing inside the nucleus had transcription functions ( Møller et al, 2018 ). A new study characterized plasma eccDNA in gouty arthritis and identified several eccDNA genes such as COL1A1 and EPB42, which were considered to be closely associated with hyperuricemia and gout ( Pang et al, 2022 ). Several genes involved in inflammation or immune response were also identified by enrichment analysis.…”