Whole genome sequencing helps team publish China’s first population blood atlas

14 viruses widely present in the Chinese population. Credit: Cell discovery (2022). DOI: 10.1038/s41421-022-00476-1

Whole genome sequencing technology can discover various known or unspecified viral sequences contained in human blood, which can provide an important database for viral infection prevention, vaccine development, viral genomics and epidemiological research. For example, many common cancers are associated with oncogenic viruses, including Epstein-Barr virus (EBV), hepatitis B and C viruses (HBV and HCV), and human papillomavirus (HPV).

In October 2022, BGI Genomics, Ruijin Hospital, Shanghai Jiao Tong University Institute of Translational Medicine leveraged BGI’s proprietary DNBSEQ sequencing platform to perform in-depth analysis of non-human genetic sequences in Whole Genome Sequencing (WGS) data ) of 10,585 people from the China Metabolic Analysis Program (ChinaMAP) and constructed the first blood virological profile of the Chinese population. The results were published in the journal Cell discovery and provide a reference for the prevention and epidemiology of viral infections.

This study established a WGS-based method to analyze viral sequences by extracting non-human gene sequences from WGS data of 10,585 individuals and identified 14 viruses widely present in the Chinese population, such as the fingerprint virus. foxgloves, herpes B virus, human endogenous retrovirus. , human adenovirus C and hepatitis B virus.

The highest detection rate was for anellovirus, with genetic sequences of fingerprint viruses including TTV (Torque teno virus) and TLMV (TTV-like minivirus) found in 76.7% of individuals; HHV-4 (Human gammaherpesvirus 4, EBV) was detected in 30.3% of individuals, higher than that reported in the European population cohort (14%).

Herpesvirus B (Betaherpesvirus) was also widely detected, with HHV7 (Human herpesvirus 7), HHV6A (Human betaherpesvirus 6A), HHV6B (human betaherpesvirus 6B) and HHV5 (Human betaherpesvirus 5, HCMV) found in 13.2%, 0.36%, 1.09% and 1.03% of individuals, respectively.

Endogenous human retrovirus K (HERV-K), human mastadenovirus C (HMV) and hepatitis B virus (HBV) were found in 8.20%, 2.41% and 1.69% of individuals, respectively. .

Additionally, the team detected HPV sequences in 50 individuals (0.47%), involving Gammapapillomavirus 1, Betapapillomavirus 1, and Alphapapillomavirus 4 subtypes.

Most monitored virus: Hepatitis B virus

Hepatitis B is a major infectious disease in China and remains one of the leading causes of liver cancer. The research team detected hepatitis B virus (HBV) sequences in 1.69% of individuals, consisting mainly of two subtypes (77%), HBV-B and HBV-C. In addition, the team analyzed viral integration events in the human genome and found HBV-B viral sequence integration in 10 samples and HBV-C viral sequence integration in 18 samples. , a finding indicating that integration events were significantly associated with greater viral sequence abundance and that there were no regions significantly enriched for HBV viral sequence integration sites on the human genome.

The team further investigated whether there is a correlation between viral infection and genetic variation through genome-wide association studies (GWAS). The results showed that a missense mutation of the ACR gene was significantly associated with HHV6 virus carriage and that the locus was enriched in East Asian populations.

HHV6 belongs to betaherpesviruses and includes two viruses with up to 90% genomic sequence identity, HHV6A and HHV6B. Although HHV6 infection is harmless to most people, studies have also shown that HHV6 infection is associated with neurological diseases such as multiple sclerosis and Alzheimer’s disease, indicating that the potential harmfulness of HHV6 infection cannot be ignored.

This insight provides an important database for future studies of the mechanism of HHV6 virus transmission, as well as genetic risk assessment of populations in regions at high risk of HHV6 infection.

In summary, this study systematically investigated viral blood group in a large-scale population using extensive WGS data based on BGI’s proprietary DNBSEQ sequencing platform and analyzed population carriage rate, l viral abundance and geographical distribution of 14 viruses.

EBV detected in 30% of individuals was found to be the most frequently carried pathogenic virus in the population, HBV viral abundance in the blood was associated with integration events, and the false- sense in ACR was significantly associated with HHV6 virus carriage. These results will provide important information for the prevention of viral infections and epidemiological studies. At the same time, it also provides references and lessons for larger population genomics projects.

Provided by BGI Genomics