Liver cancer ranks sixth in cancer incidence, and is the third leading cause of cancer-related deaths worldwide. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, which arises from hepatocytes an...Liver cancer ranks sixth in cancer incidence, and is the third leading cause of cancer-related deaths worldwide. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, which arises from hepatocytes and accounts for approximately 70%-85% of cases. Hepatitis B virus (HBV) frequently causes liver inflammation, hepatic damage and subsequent cirrhosis. Integrated viral DNA is found in 85%-90% of HBV-related HCCs. Its presence in tumors from non-cirrhotic livers of children or young adults further supports the role of viral DNA integration in hepatocarcinogenesis. Integration of subgenomic HBV DNA fragments into different locations within the host DNA is a significant feature of chronic HBV infection. Integration has two potential consequences: (1) the host genome becomes altered (“cis” effect); and (2) the HBV genome becomes altered (“trans” effect). The cis effect includes insertional mutagenesis, which can potentially disrupt host gene function or alter host gene regulation. Tumor progression is frequently associated with rearrangement and partial gain or loss of both viral and host sequences. However, the role of integrated HBV DNA in hepatocarcinogenesis remains controversial. Modern technology has provided a new paradigm to further our understanding of disease mechanisms. This review summarizes the role of HBV DNA integration in human carcinogenesis.展开更多
INTRODUCTIONHepatitis B virus (HBV) belongs to the group ofhepatovirus, a major pathogen of human acute andchronic hepatitis B[1 4], which has a very closeassociation with human hepatocellular carcinoma(HCC)[5-8], For...INTRODUCTIONHepatitis B virus (HBV) belongs to the group ofhepatovirus, a major pathogen of human acute andchronic hepatitis B[1 4], which has a very closeassociation with human hepatocellular carcinoma(HCC)[5-8], For example, a statistical data from ahospital in Shanghai showed that 80% of HCCpatients were positive for HBsAg ( personalcommunication).展开更多
Hepatitis B virus(HBV) is still a worldwide health concern. While divergent factors are involved in its pathogenesis, it is now clear that HBV RNAs, principally templates for viral proteins and viral DNAs, have divers...Hepatitis B virus(HBV) is still a worldwide health concern. While divergent factors are involved in its pathogenesis, it is now clear that HBV RNAs, principally templates for viral proteins and viral DNAs, have diverse biological functions involved in HBV pathogenesis. These functions include viral replication, hepatic fibrosis and hepatocarcinogenesis. Depending on the sequence similarities, HBV RNAs may act as sponges for host mi RNAs and may deregulate mi RNA functions, possibly leading to pathological consequences. Some parts of the HBV RNA molecule may function as viralderived mi RNA, which regulates viral replication. HBV DNA can integrate into the host genomic DNA and produce novel viral-host fusion RNA, which may have pathological functions. To date, elimination of HBVderived covalently closed circular DNA has not been achieved. However, RNA transcription silencing may be an alternative practical approach to treat HBVinduced pathogenesis. A full understanding of HBV RNA transcription and the biological functions of HBV RNA may open a new avenue for the development of novel HBV therapeutics.展开更多
Genome-wide association mapping studies(GWAS)based on Big Data are a potential approach to improve marker-assisted selection in plant breeding.The number of available phenotypic and genomic data sets in which medium-s...Genome-wide association mapping studies(GWAS)based on Big Data are a potential approach to improve marker-assisted selection in plant breeding.The number of available phenotypic and genomic data sets in which medium-sized populations of several hundred individuals have been studied is rapidly increasing.Combining these data and using them in GWAS could increase both the power of QTL discovery and the accuracy of estimation of underlying genetic effects,but is hindered by data heterogeneity and lack of interoperability.In this study,we used genomic and phenotypic data sets,focusing on Central European winter wheat populations evaluated for heading date.We explored strategies for integrating these data and subsequently the resulting potential for GWAS.Establishing interoperability between data sets was greatly aided by some overlapping genotypes and a linear relationship between the different phenotyping protocols,resulting in high quality integrated phenotypic data.In this context,genomic prediction proved to be a suitable tool to study relevance of interactions between genotypes and experimental series,which was low in our case.Contrary to expectations,fewer associations between markers and traits were found in the larger combined data than in the individual experimental series.However,the predictive power based on the marker-trait associations of the integrated data set was higher across data sets.Therefore,the results show that the integration of medium-sized to Big Data is an approach to increase the power to detect QTL in GWAS.The results encourage further efforts to standardize and share data in the plant breeding community.展开更多
Genome data of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is essential for virus diagnosis,vaccine development,and variant surveillance.To archive and integrate worldwide SARS-CoV-2 genome data,a serie...Genome data of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is essential for virus diagnosis,vaccine development,and variant surveillance.To archive and integrate worldwide SARS-CoV-2 genome data,a series of resources have been constructed,serving as a fundamental infrastructure for SARS-CoV-2 research,pandemic prevention and control,and coronavirus disease 2019(COVID-19)therapy.Here we present an over-view of extant SARS-CoV-2 resources that are devoted to genome data deposition and integration.We review deposition resources in data accessibility,metadata standardization,data curation and annotation;review integrative resources in data source,de-redundancy processing,data curation and quality assessment,and variant annotation.Moreover,we address issues that impede SARS-CoV-2 genome data integration,including low-complexity,inconsistency and absence of isolate name,sequence inconsistency,asynchronous update of genome data,and mismatched metadata.We finally provide insights into data standardization consensus and data submission guidelines,to promote SARS-CoV-2 genome data sharing and integration.展开更多
The explosion of next-generation sequencing(NGS)has enabled the widespread use of genomic data in precision medicine.Currently,several neonatal genome projects have emerged to explore the advantages of NGS to diagnose...The explosion of next-generation sequencing(NGS)has enabled the widespread use of genomic data in precision medicine.Currently,several neonatal genome projects have emerged to explore the advantages of NGS to diagnose or screen for rare genetic disorders.These projects have made remarkable achievements,but still the genome data could be further explored with the assistance of phenotype collection.In contrast,longitudinal birth cohorts are great examples to record and apply phenotypic information in clinical studies starting at the neonatal period,especially the trajectory analyses for health development or disease progression.It is obvious that efficient integration of genotype and phenotype benefits not only the clinical management of rare genetic disorders but also the risk assessment of complex diseases.Here,we first summarize the recent neonatal genome projects as well as some longitudinal birth cohorts.Then,we propose two simplified strategies by integrating genotypic and phenotypic information in precision medicine based on current studies.Finally,research collaborations,sociological issues,and future perspectives are discussed.How to maximize neonatal genomic information to benefit the pediatric population remains an area in need of more research and effort.展开更多
Structural variations (SVs) are mutations with large-scale changes (generally>50 bp) in the genome. SVs are major sources of the genetic diversity of organisms and thus are of high relevance to phenotype variations...Structural variations (SVs) are mutations with large-scale changes (generally>50 bp) in the genome. SVs are major sources of the genetic diversity of organisms and thus are of high relevance to phenotype variations, gene dosage and evolutionary genetics. Except detecting SVs through comparative genetic analyses, dozens of software had been developed based on the alignment of short-reads to a single linear genome in the past decades (Guan and Sung, 2016).展开更多
The principal reason of chronic liver disease,cirrhosis and hepatocellular carcinoma is chronic viral hepatitis all over the world.Hepatitis B virus(HBV)has some mutagenic effects on the host genome.HBV may be exhibit...The principal reason of chronic liver disease,cirrhosis and hepatocellular carcinoma is chronic viral hepatitis all over the world.Hepatitis B virus(HBV)has some mutagenic effects on the host genome.HBV may be exhibiting these mutagenic effects through integrating into the host genome,through its viral proteins or through some epigenetic mechanisms related with HBV proteins.This review aims to summarize the molecular mechanisms used by HBV for effecting host genome determined in the last decade.The focus will be on the effects of integration,HBV proteins,especially HBV X protein and epigenetic mechanisms on the host genome.These interactions between HBV and the host genome also forms the underlying mechanisms of the evolution of hepatocellular carcinoma.展开更多
文摘Liver cancer ranks sixth in cancer incidence, and is the third leading cause of cancer-related deaths worldwide. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, which arises from hepatocytes and accounts for approximately 70%-85% of cases. Hepatitis B virus (HBV) frequently causes liver inflammation, hepatic damage and subsequent cirrhosis. Integrated viral DNA is found in 85%-90% of HBV-related HCCs. Its presence in tumors from non-cirrhotic livers of children or young adults further supports the role of viral DNA integration in hepatocarcinogenesis. Integration of subgenomic HBV DNA fragments into different locations within the host DNA is a significant feature of chronic HBV infection. Integration has two potential consequences: (1) the host genome becomes altered (“cis” effect); and (2) the HBV genome becomes altered (“trans” effect). The cis effect includes insertional mutagenesis, which can potentially disrupt host gene function or alter host gene regulation. Tumor progression is frequently associated with rearrangement and partial gain or loss of both viral and host sequences. However, the role of integrated HBV DNA in hepatocarcinogenesis remains controversial. Modern technology has provided a new paradigm to further our understanding of disease mechanisms. This review summarizes the role of HBV DNA integration in human carcinogenesis.
基金This work was supported by Projects of Tackling Key Problems in ScienceTechnology from the State Science+2 种基金Technology Ministry (TJ99-LA01) Shanghai ScienceTechnology Commission (994919033 )
文摘INTRODUCTIONHepatitis B virus (HBV) belongs to the group ofhepatovirus, a major pathogen of human acute andchronic hepatitis B[1 4], which has a very closeassociation with human hepatocellular carcinoma(HCC)[5-8], For example, a statistical data from ahospital in Shanghai showed that 80% of HCCpatients were positive for HBsAg ( personalcommunication).
基金Supported by the Research Program on Hepatitis from Japan Agency for Medical Research and Development,AMED to Otsuka M,No.JP18fk0210214the Project for Cancer Research and Therapeutic Evolution(P-CREATE)from AMED to Otsuka M,No.JP19cm0106602
文摘Hepatitis B virus(HBV) is still a worldwide health concern. While divergent factors are involved in its pathogenesis, it is now clear that HBV RNAs, principally templates for viral proteins and viral DNAs, have diverse biological functions involved in HBV pathogenesis. These functions include viral replication, hepatic fibrosis and hepatocarcinogenesis. Depending on the sequence similarities, HBV RNAs may act as sponges for host mi RNAs and may deregulate mi RNA functions, possibly leading to pathological consequences. Some parts of the HBV RNA molecule may function as viralderived mi RNA, which regulates viral replication. HBV DNA can integrate into the host genomic DNA and produce novel viral-host fusion RNA, which may have pathological functions. To date, elimination of HBVderived covalently closed circular DNA has not been achieved. However, RNA transcription silencing may be an alternative practical approach to treat HBVinduced pathogenesis. A full understanding of HBV RNA transcription and the biological functions of HBV RNA may open a new avenue for the development of novel HBV therapeutics.
基金funding within the Wheat BigData Project(German Federal Ministry of Food and Agriculture,FKZ2818408B18)。
文摘Genome-wide association mapping studies(GWAS)based on Big Data are a potential approach to improve marker-assisted selection in plant breeding.The number of available phenotypic and genomic data sets in which medium-sized populations of several hundred individuals have been studied is rapidly increasing.Combining these data and using them in GWAS could increase both the power of QTL discovery and the accuracy of estimation of underlying genetic effects,but is hindered by data heterogeneity and lack of interoperability.In this study,we used genomic and phenotypic data sets,focusing on Central European winter wheat populations evaluated for heading date.We explored strategies for integrating these data and subsequently the resulting potential for GWAS.Establishing interoperability between data sets was greatly aided by some overlapping genotypes and a linear relationship between the different phenotyping protocols,resulting in high quality integrated phenotypic data.In this context,genomic prediction proved to be a suitable tool to study relevance of interactions between genotypes and experimental series,which was low in our case.Contrary to expectations,fewer associations between markers and traits were found in the larger combined data than in the individual experimental series.However,the predictive power based on the marker-trait associations of the integrated data set was higher across data sets.Therefore,the results show that the integration of medium-sized to Big Data is an approach to increase the power to detect QTL in GWAS.The results encourage further efforts to standardize and share data in the plant breeding community.
基金supported by Strategic Priority Research Program of the Chinese Academy of Sciences[XDB38030201,XDB38030400,XDB38050300]Youth Innovation Promotion Association of Chinese Academy of Sciences[2019104]。
文摘Genome data of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is essential for virus diagnosis,vaccine development,and variant surveillance.To archive and integrate worldwide SARS-CoV-2 genome data,a series of resources have been constructed,serving as a fundamental infrastructure for SARS-CoV-2 research,pandemic prevention and control,and coronavirus disease 2019(COVID-19)therapy.Here we present an over-view of extant SARS-CoV-2 resources that are devoted to genome data deposition and integration.We review deposition resources in data accessibility,metadata standardization,data curation and annotation;review integrative resources in data source,de-redundancy processing,data curation and quality assessment,and variant annotation.Moreover,we address issues that impede SARS-CoV-2 genome data integration,including low-complexity,inconsistency and absence of isolate name,sequence inconsistency,asynchronous update of genome data,and mismatched metadata.We finally provide insights into data standardization consensus and data submission guidelines,to promote SARS-CoV-2 genome data sharing and integration.
基金the Ministry of Science and Technology National Key Research and Development Program(2020YFC2006402)a Project supported by Shanghai Municipal Science and Technology Major Project(2017SHZDZX01).
文摘The explosion of next-generation sequencing(NGS)has enabled the widespread use of genomic data in precision medicine.Currently,several neonatal genome projects have emerged to explore the advantages of NGS to diagnose or screen for rare genetic disorders.These projects have made remarkable achievements,but still the genome data could be further explored with the assistance of phenotype collection.In contrast,longitudinal birth cohorts are great examples to record and apply phenotypic information in clinical studies starting at the neonatal period,especially the trajectory analyses for health development or disease progression.It is obvious that efficient integration of genotype and phenotype benefits not only the clinical management of rare genetic disorders but also the risk assessment of complex diseases.Here,we first summarize the recent neonatal genome projects as well as some longitudinal birth cohorts.Then,we propose two simplified strategies by integrating genotypic and phenotypic information in precision medicine based on current studies.Finally,research collaborations,sociological issues,and future perspectives are discussed.How to maximize neonatal genomic information to benefit the pediatric population remains an area in need of more research and effort.
文摘Structural variations (SVs) are mutations with large-scale changes (generally>50 bp) in the genome. SVs are major sources of the genetic diversity of organisms and thus are of high relevance to phenotype variations, gene dosage and evolutionary genetics. Except detecting SVs through comparative genetic analyses, dozens of software had been developed based on the alignment of short-reads to a single linear genome in the past decades (Guan and Sung, 2016).
文摘The principal reason of chronic liver disease,cirrhosis and hepatocellular carcinoma is chronic viral hepatitis all over the world.Hepatitis B virus(HBV)has some mutagenic effects on the host genome.HBV may be exhibiting these mutagenic effects through integrating into the host genome,through its viral proteins or through some epigenetic mechanisms related with HBV proteins.This review aims to summarize the molecular mechanisms used by HBV for effecting host genome determined in the last decade.The focus will be on the effects of integration,HBV proteins,especially HBV X protein and epigenetic mechanisms on the host genome.These interactions between HBV and the host genome also forms the underlying mechanisms of the evolution of hepatocellular carcinoma.
