全基因組測序助力團隊發布首個中國人口血圖譜

StephenW

全基因組測序助力團隊發布首個中國人口血圖譜

華大基因
中國人群中廣泛存在的14種病毒。 圖片來源：Cell Discovery（2022 年）。 DOI: 10.1038/s41421-022-00476-1

全基因組測序技術可以發現人體血液中所含的各種已知或未知的病毒序列，可為病毒感染預防、疫苗研製、病毒基因組學和流行病學研究提供重要的數據庫。 例如，許多常見癌症都與致癌病毒有關，包括愛潑斯坦-巴爾病毒 (EBV)、乙型和丙型肝炎病毒（HBV 和 HCV）以及人乳頭瘤病毒 (HPV)。

2022年10月，上海交通大學轉化醫學研究院瑞金醫院華大基因利用華大基因自主研發的DNBSEQ測序平台，對中國代謝組學10585人的全基因組測序（WGS）數據中的非人基因序列進行深度分析 Analysis Program (ChinaMAP)，並構建了第一個中國人群的血液病毒學概況。 該成果發表在《Cell Discovery》雜誌上，為病毒感染預防和流行病學研究提供參考。

本研究通過從 10585 個人的 WGS 數據中提取非人類基因序列，建立了基於 WGS 的病毒序列分析方法，鑑定出指紋病毒、乙型皰疹病毒、人內源性逆轉錄病毒等 14 種廣泛存在於中國人群中的病毒。 、人類腺病毒 C 和乙型肝炎病毒。

檢出率最高的是指環病毒，在76.7%的個體中發現指紋病毒基因序列，包括TTV（Torque teno virus）和TLMV（TTV-like mini virus）； 在 30.3% 的個體中檢測到 HHV-4（人類伽瑪皰疹病毒 4，EBV），高於歐洲人群隊列中報告的比例 (14%)。

皰疹病毒 B (Betaherpesvirus) 也被廣泛檢測到，HHV7（人類皰疹病毒 7）、HHV6A（人類β皰疹病毒 6A）、HHV6B（人類β皰疹病毒 6B）和 HHV5（人類β皰疹病毒 5，HCMV）在 13.2%、0.36%、1.09 中被發現 % 和 1.03% 的個體。
左：乙型肝炎病毒在人類基因組上的整合位點； 右圖：乙型肝炎病毒基因組的整合位點。 圖片來源：Cell Discovery（2022 年）。 DOI: 10.1038/s41421-022-00476-1

人內源性逆轉錄病毒 K (HERV-K)、人乳腺腺病毒 C (HMV) 和乙型肝炎病毒 (HBV) 分別在 8.20%、2.41% 和 1.69% 的個體中被發現。

此外，該團隊在 50 個個體 (0.47%) 中檢測到 HPV 序列，涉及亞型 Gammapapillomavirus 1、Betapapillomavirus 1 和 Alphapapillomavirus 4。

最受監控的病毒：乙型肝炎病毒

乙型肝炎是我國主要的傳染病，目前仍是導致肝癌的主要原因之一。 研究小組在 1.69% 的個體中檢測到乙型肝炎病毒 (HBV) 序列，主要由兩種亞型 (77%) 組成，即 HBV-B 和 HBV-C。 此外，該團隊分析了人類基因組中的病毒整合事件，發現 10 個樣本中存在 HBV-B 病毒序列整合，18 個樣本中存在 HBV-C 病毒序列整合，結果表明整合事件與較高的病毒序列豐度顯著相關，並且 人類基因組上的 HBV 病毒序列整合位點區域沒有顯著富集。

該團隊通過全基因組關聯研究（GWAS）進一步研究了病毒感染與遺傳變異之間是否存在相關性。 結果表明，ACR 基因的錯義突變與 HHV6 病毒攜帶顯著相關，並且該基因座在東亞人群中富集。
HHV6 感染的全基因組關聯分析（曼哈頓圖）。 圖片來源：Cell Discovery（2022 年）。 DOI: 10.1038/s41421-022-00476-1

HHV6 屬於貝塔皰疹病毒，包括基因組序列同一性高達 90% 的兩種病毒 HHV6A 和 HHV6B。 雖然HHV6感染對大多數人無害，但研究也發現HHV6感染與多發性硬化症、阿爾茨海默病等神經系統疾病有關，表明HHV6感染的潛在危害不容忽視。

這一見解為今後研究HHV6病毒的傳播機制以及HHV6感染高危地區人群的遺傳風險評估提供了重要的數據庫。

綜上所述，本研究基於華大基因自有的DNBSEQ測序平台，利用深度WGS數據系統調查了大規模人群的血液病毒群，分析了14種病毒的人群攜帶率、病毒豐度和地理分佈。
結果發現，在 30% 的個體中檢測到的 EBV 是人群中最常見的致病病毒，血液中的 HBV 病毒豐度與整合事件相關，ACR 中的錯義突變與 HHV6 病毒攜帶顯著相關。 這些發現將為病毒感染預防和流行病學研究提供重要信息。 同時也為更大規模的人群基因組計劃提供了參考和借鑒。
更多信息：Jia Guo 等人，來自 ChinaMAP 的 10,585 人的血液病毒組，Cell Discovery (2022)。 DOI: 10.1038/s41421-022-00476-1

StephenW

Whole genome sequencing helps team release the first Chinese population blood atlas

by BGI Genomics
14 viruses that are 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 genomic and epidemiological research. For example, numerous 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 conduct an in-depth analysis of nonhuman genetic sequences in the whole genome sequencing (WGS) data of 10,585 people from 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 viral infection prevention and epidemiology.

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 that are widely present in the Chinese population, such as fingerprint virus, herpes B virus, human endogenous retrovirus, human adenovirus C, and hepatitis B virus.

The highest detection rate was for Anellovirus, with fingerprint virus genetic sequences including TTV (Torque teno virus) and TLMV (TTV-like mini virus) 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.
Left: integration sites of hepatitis B virus on the human genome; Right: integration sites of hepatitis B virus genome. Credit: Cell Discovery (2022). DOI: 10.1038/s41421-022-00476-1

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

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

Most monitored virus: Hepatitis B virus

Hepatitis B is a major infectious disease in China and is still one of the major 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. Further, 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 result indicating that integration events were significantly associated with higher viral sequence abundance and that there were no significantly enriched regions of 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 in the ACR gene was significantly associated with HHV6 viral carriage, and the locus was enriched in East Asian populations.
Genome-wide association analysis of HHV6 infection (Manhattan plot). Credit: Cell Discovery (2022). DOI: 10.1038/s41421-022-00476-1

HHV6 belongs to the 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 found that HHV6 infection is associated with neurological diseases such as multiple sclerosis and Alzheimer's disease, indicating the potential harmfulness of HHV6 infection cannot be ignored.

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

In summary, this study systematically investigated the blood viral group in a large-scale population using in-depth WGS data based on BGI's proprietary DNBSEQ sequencing platform and analyzed the population carriage rate, viral abundance and geographic distribution of 14 viruses.
It was found that EBV detected in 30% of individuals was the most frequent pathogenic virus carried in the population, HBV viral abundance in blood was associated with integration events, and the missense mutation in ACR was significantly associated with HHV6 virus carriage. These findings will provide important information for viral infection prevention and epidemiological studies. At the same time, it also provides references and lessons for larger population genomic projects.
More information: Jia Guo et al, The blood virome of 10,585 individuals from the ChinaMAP, Cell Discovery (2022). DOI: 10.1038/s41421-022-00476-1

StephenW

https://medicalxpress.com/news/2 ... ese-population.html