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HBV Integration Induces Complex Interactions between Host and Viral Genomic Functions at the Insertion Site

Journal of Clinical and Translational Hepatology 2021年第3期9卷 399-408页

作者： Dake Zhang Ke Zhang Urlike Protzer changqing zeng Beijing Advanced Innovation Centre for Biomedical Engineering Key Laboratory for Biomechanics and Mechanobiology of Ministry of EducationSchool of Biological Science and Medical EngineeringBeihang UniversityBeijingChina SCG Cell Therapy Pte.Ltd Singapore Institute of Virology Technical University of Munich/Helmholtz Zentrum MünchenMunichGermany German Center for Infection Research(DZIF) MunichGermany Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijingChina University of Chinese Academy of Sciences BeijingChina

Hepatitis B virus(HBV),one of the well-known DNA oncogenic viruses,is the leading cause of hepatocellular carcinoma(HCC).In infected hepatocytes,HBV DNA can be integrated into the host genome through an insertional mutagenesis process inducing *** of the genomic features surrounding integration sites will deepen our understanding of mechanisms underlying ***,the quantity and biological activity of integration sites may reflect the DNA damage within affected cells or the potential survival benefits they may *** wellknown human genomic features include repeat elements,particular regions(such as telomeres),and frequently interrupted genes(e.g.,telomerase reverse transcriptase[***],lysine methyltransferase 2B[***2B],cyclin E1[CCNE1],and cyclin A2[CCNA2]).Consequently,distinct genomic features within diverse integrations differentiate their biological ***,accumulating evidence has shown that viral proteins produced by integrants may cause cell damage even after the suppression of HBV *** integration-derived gene products can also serve as tumor markers,promoting the development of novel therapeutic strategies for *** integrants can be single copy or multiple copies of different fragments with complicated rearrangement,which warrants elucidation of the whole viral integrant arrangement in future *** of these considerations underlie an urgent need to develop novel methodology and technology for sequence characterization and function evaluation of integration events in chronic hepatitis B-associated disease progression by monitoring both host genomic features and viral *** endeavor may also serve as a promising solution for evaluating the risk of tumorigenesis and as a companion diagnostic for designing therapeutic strategies targeting integration-related disease complications.

关键词： Double-strand break Chimeric reads Junction reads Fusion transcript Virus cellular junction Virus cell junction Virus host junction

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Evolutionary significance of selected EDAR variants in Tibetan high-altitude adaptations

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Science China(Life Sciences) 2018年第1期61卷 68-78页

作者： Jianming Shao Muhammad Sohail Raza Basang Zhuoma changqing zeng CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of Genomics Chinese Academy of Sciences Beijing 100101 China University of Chinese Academy of Sciences Beijing 100049 China The Innovation Center of Excellence on Science and Education of Life Sciences Chinese Academy of Sciences Beijing 100049 China Collaborative Innovation Center of Genetics and Development Shanghai 200438 China Medical College of Tibet University Lhasa 850002 China

Humans have been exposed to many environmental challenges since their evolutionary origins in Africa and subsequent migrations to the rest of the world. A severe environmental challenge to human migrants was hypoxia caused by low barometric oxygen pressure at high altitudes. Several genome-wide scans have elucidated the genetic basis of human high-altitude ***, the dearth of functional variant information has led to the successful association of only a few candidate genes. In the present study, we employed a candidate gene approach and re-sequenced the EDAR locus in 45 Tibetan individuals to identify mutations involved in hypoxia adaptation. We identified 10 and five quantitative trait-associated mutations for oxygen saturation (SaO_2) and blood platelet count, respectively, at the EDAR locus. Among these, rs10865026 and rs3749110 (associated with SaO_2 and platelet count, respectively) were identified as functional candidate targets. These data demonstrate that EDAR has undergone natural selection in recent human history and indicate an important role of EDAR variants in Tibetan high-altitude adaptations.

关键词： Tibetan high altitude adaptation EDAR

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Scanning for signatures of geographically restricted selection based on population genomics analysis

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Chinese Science Bulletin 2007年第19期52卷 2649-2656页

作者： DENG LiBin TANG XiaoLi KANG Jian WANG QingYun zeng changqing Beijing Institute of Genomics Chinese Academy of Sciences Beijing 101300 China Graduate University of Chinese Academy of Sciences Beijing 100049 China Department of Mathematical Sciences School of Science Tsinghua University Beijing 100084 China School of Mathematical Sciences Beijing Normal University Beijing 100875 China

Natural selection, as the driving force of human evolution, has direct impact on population differentiation. However, it is still unclear to what extent the genetic differentiation has been caused by natural selection. To explore this question, we performed a genome-wide scan with single nucleotide polymorphism (SNP) data from the International HapMap Project. Single locus FST analysis was applied to assess the frequency difference among populations in autosomes. Based on the empirical distribution of FST, we identified 12669 SNPs correlating to population differentiation and 1853 candidate genes subjected to geographic restricted natural selection. Further interpretation of gene ontogeny revealed 121 categories of biological process with the enrichments of candidate genes. Our results suggest that natural selection may play an important role in human population differentiation. In addition, our analysis provides new clues as well as research methods for our understanding of population differentiation and natural selection.

关键词：单核苷酸基因多态性染色体扫描技术

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The study of neighboring nucleotide composition and transition/transversion bias

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Science China(Life Sciences) 2006年第4期49卷 395-402页

作者： ZHAO Hui LI Qizhai LI Jun zeng changqing HU Songnian YU Jun Beijing Institute of Genomics Chinese Academy of SciencesBeijing 100030China Academy of Mathematics and Systems Science Chinese Academy of SciencesBeijing 100080China Graduate University of Chinese Academy of Sciences Beijing 100039China

Base substitution is one of the raw fuels that produce genetic variation; drive evolution. Recent studies have shown that the genome components affect mutation patterns to some extent. In order to infer the correlation between the Transition/Transversion ratio (Ts/Tv); the number of immediately adjacent A&T nucleotides, we investigated 3611007 Oryza sativa SNPs (including 45462 coding SNPs,; 242811 intronic SNPs); 32019 Arabidopsis SNPs. The results show that Ts/Tv is negatively correlated with the number of immediately adjacent A&T in O. Sativa; Arabidopsis. We further calculated AT2 (the number of SNPs whose immediately adjacent nucleotides are either A or T); AT0 (the number of SNPs whose immediately adjacent nucleotides are either C or G) for all 6 types of SNPs. C/G SNP of O. sativa; Arabidopsis has the highest AT2/AT0, which denotes C/G SNP may be influenced by the adjacent A&T nucleotides mostly. For SNPs in O. sativa, the neighboring effect of A&T nucleotides is limited to 2 nucleotides on both sides; for SNPs in Arabidopsis, the effect extends no more than 4 nucleotides on both sides.

关键词： Base substitution SNP Transition bias Transition Transversion

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In vitro Transcriptome Analysis of Two Chinese Isolates of Streptococcus suis Serotype 2

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Genomics, Proteomics & Bioinformatics 2014年第6期12卷 266-275页

作者： Dake Zhang Nan Du Sufang Ma Qingtao Hu Guangwen Lu Wei Chen changqing zeng CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of Sciences CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of Sciences University of Chinese Academy of Sciences

The Streptococcus suis serotype 2（S. suis 2） isolates 05ZYH33 and 98HAH33 have caused severe human infections in China. Using a strand-specific RNA-seq analysis, we compared the in vitro transcriptomes of these two Chinese isolates with that of a reference strain（P1/7）. In the89 K genomic island that is specific to these Chinese isolates, a toxin–antitoxin system showed relatively high levels of transcription among the S. suis. The known virulence factors with high transcriptional activity in these two highly-pathogenic strains are mainly involved in adhesion, biofilm formation, hemolysis and the synthesis and transport of the outer membrane protein. Furthermore,our analysis of novel transcripts identified over 50 protein-coding genes with one of them encoding a toxin protein. We also predicted over 30 small RNAs（s RNAs） in each strain, and most of them are involved in riboswitches. We found that six s RNA candidates that are related to bacterial virulence, including csp A and rli38, are specific to Chinese isolates. These results provide insight into the factors responsible for the difference in virulence among the different S. suis 2 isolates.

关键词： Streptococcus suis serotype 2 Transcriptome Novel transcripts s RNA Virulence factor

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Genetic Flux Between H1 and H2 Haplotypes of the 17q21.31 Inversion in European Population

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Genomics, Proteomics & Bioinformatics 2011年第3期9卷 113-118页

作者： Libin Deng Xiaoli Tang Xiangwen Hao Wei Chen Jiari Lin Yangyu Yu Dake Zhang changqing zeng Faculty of Basic Medical Science Nanchang University Nanchang 330006 China Beijing Institute of Genomics Chinese Academy of Sciences Beijing 100029 China Institute of Translational Medicine Nanchang University Nanchang 330006 China

The chromosome 17q21.31 inversion is a 900-kb common structural polymorphism found primarily in European population. Although the genetic flux within inversion region was assumed to be considerable suppressed, it is still unclear about the details of genetic exchange between the H1 （non-inverted sequence） and H2 （inverted sequence） haplotypes of this inversion. Here we describe a refmed map of genetic exchanges between pairs of gene arrangements within the 17q21.31 region. Using HapMap phase II data of 1,546 single nucleotide polymorphisms, we successfully deduced 96 H1 and 24 H2 haplotypes in European samples by neighbor-joining tree reconstruction. Furthermore, we identified 15 and 26 candidate tracts with reciprocal and non-reciprocal genetic exchanges, respectively. In all 15 regions harboring reciprocal exchange, haplotypes reconstructed by clone sequencing did not support these exchange events, suggesting that such signals of exchange between two sister chromosomes in certain heterozygous individual were caused by phasing error regions. On the other hand, the finished clone sequencing across 4 of 26 tracts with non-reciprocal genetic flux confirmed that this kind of genetic exchange was caused by gene conversion. In summary, as crossover between pairs of gene arrangements had been considerably suppressed, gene conversion might be the most important mechanism for genetic exchange at 17q21.31.

关键词： genetic flux inversion haplotype polymorphism

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Building and sharing medical cohorts for research

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The Innovation 2024年第3期5卷 23-24页

作者： Guo-Bo Chen Siyang Liu Lei Zhang Tao Huang Xiaohua Tang Yixue Li changqing zeng Department of Genetic and Genomic Medicine Zhejiang Provincial People’s HospitalAffiliated People’s Hospital of Hangzhou Medical CollegeHangzhou 310014China Ningbo Institute of Life and Health Industry University of Chinese Academy of SciencesNingbo 315000China School of Public Health(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhen 518017China China National GeneBank Shenzhen 518116China Shanghai Institute of Nutrition and Health Chinese Academy of SciencesShanghai 200031China Wenzhou Central Hospital Dingli Clinical Medical School of Wenzhou Medical UniversityWenzhou 325000China Guangzhou Laboratory Guangzhou 510320China Henan Academy of Sciences Zhengzhou 450046China

Cohort studies are costly and time *** require not only laboratory equipment and assays but also collaboration from participants and health *** to cost constraints,they are often confined to a specific ***,they play a crucial role in providing fundamental insights for medical advancements,shedding light on the origins of diseases,and acting in socioeconomic influence in policy making.

关键词： consuming constraints insight

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A Long Type of TBCK Is a Novel Cytoplasmic and Mitotic Apparatus-Associated Protein Likely Suppressing Cell Proliferation

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Journal of Genetics and Genomics 2014年第2期41卷 69-72页

作者： Jin Wu Qianyi Li Yan Li Jing Lin Dong Yang Guixin Zhu Limin Wang Dacheng He Guanting Lu changqing zeng Laboratory of Disease Genomics and Individualized Medicine Beijing Institute of GenomicsChinese Academy of Sciences University of Chinese Academy of Sciences Key Laboratory for Cell Proliferation and Regulation of the Ministry of Education Beijing Normal University

Autoantibodies from patients with various connective tissue diseases have been shown to be specific probes that can detect cellular structures, including centrosome, centromere/kineto- chore, spliceosome, Golgi comple... 详细信息

关键词： Cell TBC A Long Type of TBCK Is a Novel Cytoplasmic and Mitotic Apparatus-Associated Protein Likely Suppressing Cell Proliferation

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High Throughput SNP Genotyping with Two Mini-sequencing Assays

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Acta Biochimica et Biophysica Sinica 2004年第6期36卷 379-384页

作者： Chunqing LUO1,2#, Libin DENG1#, and changqing zeng1,2* The Institute of Genetic and Developmental Biology, the Chinese Academy of Sciences, Beijing 100101, China 2Beijing Genomics Institute, the Chinese Academy of Sciences, Beijing 101300, China The Institute of Genetic and Developmental Biology the Chinese Academy of SciencesBeijing 100101 China Beijing Genomics Institute the Chinese Academy of SciencesBeijing 101300 China

Two mini-sequencing methods, FP-TDI (template-directed dye-terminator incorporation with fluorescence-polarization) and MassArray (matrix assisted laser desorption ionization time of flight detection mass spectrometry), were optimized. A numeric standard was introduced to evaluate the SNP scoring quality of FP-TDI assay, thus made the optimization work easier. At the same time, using multi-PCR technology, 8-plex genotyping of MassArray assay was successfully carried out, some softwares were developed and the data process of MassArray was highly automated. Then these two methods were applied to high throughput SNP genotyping, the accuracy, efficiency and robustness were compared. The result shows FP-TDI is more sensitive to the concentration of SNPprimer and PCR product, as well as extension cycles, the SNPprimer length of FP-TDI should be 24–30 bp long, whereas MassArray assay prefers to be as short as only 16 *** 6440 SNP sites of human chromosome 3 were genotyped in a sample of 90 individuals, 4792 sites by FP-TDI assay and 1648 sites by MassArray assay, the success rates of FP-TDI and MassArray were 67.7% and 93.6% respectively. The throughput of MassArray was higher than FP-TDI, and the cost of MassArray was lower, MassArray was more suitable for high throughput SNP genotyping.

关键词： SNP genotyping FP-TDI MassArray high throughput

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Overview of HBV whole genome data in public repositories and the Chinese HBV reference sequences

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Progress in Natural Science:Materials International 2008年第1期18卷 13-20页

作者： Guanghua Wu a,b, Huiguo Ding c, changqing zeng b,* a Graduate School of Chinese Academy of Sciences, Beijing 100049, China b Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 101300, China c Beijing Youan Hospital, Capital Medical University, Beijing 100069, China Graduate School of Chinese Academy of Sciences Beijing 100049 China Beijing Institute of Genomics Chinese Academy of Sciences Beijing 101300 China Beijing Youan Hospital Capital Medical University Beijing 100069 China

The number of Hepatitis B virus (HBV) whole genomic sequences in public nucleotide databases (GenBank, EMBL, and DDBJ) had reached 866 by January 1, 2007. Coming from 46 countries and regions, these sequences were categorized as eight genotypes (A–H). With the statistical and phylogenetic analysis on all available complete genomic data of HBV, we here present an overview of HBV sequences in public databases. From all registered 229 HBV genomes in Chinese regions as well as 59 sequencing data from our research group, we report the establishment of reference sequences of HBV strains prevailing in China. These analyses provide clues for the effects of HBV genotypes in host clinical progressions, geographic distribution of the infection, and the viral evolutionary history. Moreover, the viral sequence reference would be helpful in the identiffcation of various HBV mutations. Based on the analysis of various public databases, we suggest that the Chinese HBV database with the clinical information should be constructed.

关键词： Public databases HBV genomic sequences Genotype Subtype Chinese reference sequences

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