The molecular characterization of plasma extrachromosomal circular DNA in myasthenia gravis
Objective To analyze molecular features and potential functions of plasma extrachromosomal circular DNA(eccDNA),we performed full-length sequencing of eccDNA in plasma from patients with myasthenia gravis(MG).This study preliminarily explored the mechanism of eccDNA in the pathogenesis of MG.Methods Plasma samples were collected from two MG patients and two sex-and age-matched healthy individuals.EccDNA of 4 plasma samples were sequenced at full length based on a novel technology platform of rolling circle amplification(RCA)and nanopore sequencing.Combined with bioinformatics analysis,we compared the differences in size distribution,chromosomal origin,genomic element distribution,and functional enrichment of eccDNA between MG patients and 2 healthy adults.Results The plasma eccDNA with a length of 250-500 bp was most distributed both in the MG patient group and the healthy control group.EccDNA samples showed another distribution peak between 150-300 bp in the MG patient group,while it was extremely low in the healthy control group.In the healthy control group,eccDNA was most distributed on chromosome 1,while in the MG patient group,eccDNA was most distributed on chromosome 2.The proportion of eccDNA-derived genomic elements of MG patients were higher than those of healthy controls in the intronic and distal intergenic regions,while the propotion in the exonic regions were lower than those of healthy controls.Compared with healthy controls,the pathways enriched in eccDNA differential genes in the MG patient group were mostly related to chloride channel activity,chloride transmembrane transport,calcium binding and cellular signaling.Conclusions In this study,we found that differences in the molecular characteristics(size distribution,chromosomal origin,genomic element distribution,and functional enrichment)of plasma eccDNA were obvious between MG patients and healthy individuals,suggesting that eccDNA may affect the development of MG through potential functions such as regulation of gene expression,cell signaling,synaptic development,and regulation of immune function.In the future,eccDNA may be used as a novel biomarker for early diagnosis and monitoring of the efficacy of MG.
extrachromosomal circular DNAmyasthenia gravisrolling circle amplificationnanopore sequencing technology
万方数据
维普
