Characterization of extrachromosomal circular DNA for human dilated cardiomyopathy

Extrachromosomal circular DNAs (eccDNAs) are prevalent in different tumors, and have been shown to be important oncogenic drivers. While recent studies have found many eccDNAs in non-tumor cells, to date, the nature and characteristics of eccDNAs in human heart failure are rarely known. In this study, we provided a comprehensive analysis of eccDNAs in human heart failure caused by dilated cardiomyopathy (DCM). Using the Circle-Seq method, we identified the expression profile of eccDNAs in heart samples from DCM patients and healthy controls. Most eccDNAs were less than 1kb and enriched in two peaks. Analysis of the genomic distribution of eccDNAs revealed that eccDNAs were derived from all chromosomes and half of these eccDNAs carried at least one gene or gene fragment. Most eccDNAs originated from 5’UTR, 3’UTR, CpG island, long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs). In addition, eccDNAs were more enriched on gene-rich chromosomes 17 and 19. In conclusion, our work delineated the eccDNAs profiling of human healthy heart and DCM and explored potential functions of eccDNAs in the development of DCM. EccDNA expression profiles of of dilated cardiomyopathy patients and healthy controls were generated by high-throughput sequencing