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http://dx.doi.org/10.5808/gi.22047

Metagenomic analysis of viral genes integrated in whole genome sequencing data of Thai patients with Brugada syndrome  

Suwalak Chitcharoen (Program in Bioinformatics and Computational Biology, Graduate School, Chulalongkorn University)
Chureerat Phokaew (Center of Excellence for Medical Genomics, Medical Genomics Cluster, Faculty of Medicine, Chulalongkorn University)
John Mauleekoonphairoj (Department of Medicine, Faculty of Medicine, Center of Excellence in Arrhythmia Research Chulalongkorn University, Chulalongkorn University)
Apichai Khongphatthanayothin (Department of Medicine, Faculty of Medicine, Center of Excellence in Arrhythmia Research Chulalongkorn University, Chulalongkorn University)
Boosamas Sutjaporn (Excellence Center for Genomics and Precision Medicine, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society)
Pharawee Wandee (Department of Medicine, Faculty of Medicine, Center of Excellence in Arrhythmia Research Chulalongkorn University, Chulalongkorn University)
Yong Poovorawan (Department of Pediatrics, Faculty of Medicine, Chulalongkorn University)
Koonlawee Nademanee (Department of Medicine, Faculty of Medicine, Center of Excellence in Arrhythmia Research Chulalongkorn University, Chulalongkorn University)
Sunchai Payungporn (Center of Excellence in Systems Microbiology, Department of Biochemistry, Faculty of Medicine, Chulalongkorn University)
Publication Information
Genomics & Informatics / v.20, no.4, 2022 , pp. 44.1-44.13 More about this Journal
Abstract
Brugada syndrome (BS) is an autosomal dominant inheritance cardiac arrhythmia disorder associated with sudden death in young adults. Thailand has the highest prevalence of BS worldwide, and over 60% of patients with BS still have unclear disease etiology. Here, we performed a new viral metagenome analysis pipeline called VIRIN and validated it with whole genome sequencing (WGS) data of HeLa cell lines and hepatocellular carcinoma. Then the VIRIN pipeline was applied to identify viral integration positions from unmapped WGS data of Thai males, including 100 BS patients (case) and 100 controls. Even though the sample preparation had no viral enrichment step, we can identify several virus genes from our analysis pipeline. The predominance of human endogenous retrovirus K (HERV-K) viruses was found in both cases and controls by blastn and blastx analysis. This study is the first report on the full-length HERV-K assembled genomes in the Thai population. Furthermore, the HERV-K integration breakpoint positions were validated and compared between the case and control datasets. Interestingly, Brugada cases contained HERV-K integration breakpoints at promoters five times more often than controls. Overall, the highlight of this study is the BS-specific HERV-K breakpoint positions that were found at the gene coding region "NBPF11" (n = 9), "NBPF12" (n = 8) and long non-coding RNA (lncRNA) "PCAT14" (n = 4) region. The genes and the lncRNA have been reported to be associated with congenital heart and arterial diseases. These findings provide another aspect of the BS etiology associated with viral genome integrations within the human genome.
Keywords
Brugada syndrome; human endogenous retrovirus K; metagenome; VIRIN; virus integration breakpoint; whole genome sequencing;
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