tmRNA,a combination of a tRNA-related fragment and a small mRNA fragment,was confirmed as the integration site of genomic islands(GIs).Using sequence alignment and comparative genomics,68 GIs associated with tmRNA gen...tmRNA,a combination of a tRNA-related fragment and a small mRNA fragment,was confirmed as the integration site of genomic islands(GIs).Using sequence alignment and comparative genomics,68 GIs associated with tmRNA genes were identified among 13 genera of Enterobacteriaceae.Among them,53 GIs were found in Escherichia coli and Salmonella enterica.Among these 53 GIs,tandem GIs were verified in eight S.enterica and two E.coli chromosomes.The downstream regions of the tmRNA genes in most of the E.coli and S.enterica chromosomes include one GI or tandem GIs region and a remnant variable region distal to the tmRNA.The chronology of integration of tandem GIs into the genome indicated that GIs farther from the tmRNA were incorporated into the genome earlier than those nearer from the tmRNA.The integrases of the tmRNA gene-associated GIs can be further categorized into three subtypes:HP1 integrases,PhiCTX integrases,and P4 integrases,which are the most predominant.The GIs were first integrated into the chromosome by the P4 integrase,subsequently by the PhiCTX integrase,and finally by the HP1 integrase.Thus,the tmRNA gene is an important site for investigating the genetics and evolution of tandem GIs.展开更多
Oncovirus infection is crucial in human malignancies.Certain oncoviruses can lead to structural variations in the human genome known as viral genomic integration,which can contribute to tumorigenesis.Existing viral in...Oncovirus infection is crucial in human malignancies.Certain oncoviruses can lead to structural variations in the human genome known as viral genomic integration,which can contribute to tumorigenesis.Existing viral integration detection tools differ in their underlying algorithms pinpointing different aspects or features of viral integration phenomenon.We discuss about major procedures in performing viral integration detection.More importantly,we provide a technical update on Virus-Clip to facilitate its usage on the latest human genome builds(hg19 and hg38)and the adoption of multi-thread mode for faster initial read alignment.By comparing the execution of Virus-Clip using single-thread and multi-thread modes of read alignment on targeted-panel sequencing data of HBV-associated hepatocellular carcinoma patients,we demonstrate the marked improvement of multi-thread mode in terms of significantly reduced execution time,while there is negligible difference in memory usage.Taken together,with the current update of Virus-Clip,it will continue supporting the in silico detection of oncoviral integration for better understanding of various human malignancies.展开更多
针对面向整个全基因组关联研究(genome-wide association studies,GWAS)未覆盖基因组区的数据集成问题,提出基于自训练的半监督机器学习实现的语意映射技术应用于该研究领域的方法。研究结果表明:该方法能有效实现对整个GWAS未覆盖基因...针对面向整个全基因组关联研究(genome-wide association studies,GWAS)未覆盖基因组区的数据集成问题,提出基于自训练的半监督机器学习实现的语意映射技术应用于该研究领域的方法。研究结果表明:该方法能有效实现对整个GWAS未覆盖基因组区的自动的语意映射,精度达到94.2%,召回率达到97.5%,能有效降低对人类专家的依赖程度,实现对整个GWAS未覆盖基因组区数据的快捷有效集成。展开更多
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
Asthma,a chronic respiratory disease with a global prevalence of approximately 300 million individuals,presents a significant societal and economic burden.This multifaceted syndrome exhibits diverse clinical phenotype...Asthma,a chronic respiratory disease with a global prevalence of approximately 300 million individuals,presents a significant societal and economic burden.This multifaceted syndrome exhibits diverse clinical phenotypes and pathogenic endotypes influenced by various factors.The advent of omics technologies has revolutionized asthma research by delving into the molecular foundation of the disease to unravel its underlying mechanisms.Omics technologies are employed to systematically screen for potential biomarkers,encompassing genes,transcripts,methylation sites,proteins,and even the microbiome components.This review provides an insightful overview of omics applications in asthma research,with a special emphasis on genetics,transcriptomics,epigenomics,and the microbiome.We explore the cutting-edge methods,discoveries,challenges,and potential future directions in the realm of asthma omics research.By integrating multi-omics and non-omics data through advanced sta-tistical techniques,we aspire to advance precision medicine in asthma,guiding diagnosis,risk assessment,and personalized treatment strategies for this heterogeneous condition.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
Microarray and deep sequencing technologies have provided unprecedented opportunities for mapping genome mutations,RNA transcripts,transcription factor binding,and histone modifications at high resolution at the genom...Microarray and deep sequencing technologies have provided unprecedented opportunities for mapping genome mutations,RNA transcripts,transcription factor binding,and histone modifications at high resolution at the genome-wide level.This has revolutionized the way in which transcriptomes,regulatory networks and epigenetic regulations have been studied and large amounts of heterogeneous data have been generated.Although efforts are being made to integrate these datasets unbiasedly and efficiently,how best to do this still remains a challenge.Here we review major impacts of high-throughput genome-wide data generation,their relevance to human diseases,and various bioinformatics approaches for data integration.Finally,we provide a case study on inflammatory diseases.展开更多
基金supported by the National Natural Science Foundation of China (30821005 and 30870075)the National Basic Research Program of China (2009CB118906)the Shanghai Leading Academic Discipline Project (B203)
文摘tmRNA,a combination of a tRNA-related fragment and a small mRNA fragment,was confirmed as the integration site of genomic islands(GIs).Using sequence alignment and comparative genomics,68 GIs associated with tmRNA genes were identified among 13 genera of Enterobacteriaceae.Among them,53 GIs were found in Escherichia coli and Salmonella enterica.Among these 53 GIs,tandem GIs were verified in eight S.enterica and two E.coli chromosomes.The downstream regions of the tmRNA genes in most of the E.coli and S.enterica chromosomes include one GI or tandem GIs region and a remnant variable region distal to the tmRNA.The chronology of integration of tandem GIs into the genome indicated that GIs farther from the tmRNA were incorporated into the genome earlier than those nearer from the tmRNA.The integrases of the tmRNA gene-associated GIs can be further categorized into three subtypes:HP1 integrases,PhiCTX integrases,and P4 integrases,which are the most predominant.The GIs were first integrated into the chromosome by the P4 integrase,subsequently by the PhiCTX integrase,and finally by the HP1 integrase.Thus,the tmRNA gene is an important site for investigating the genetics and evolution of tandem GIs.
基金the National Natural Science Foundation of China(81872222)Hong Kong Research Grants Council Theme-based Research Scheme(T12-704/16-R)。
文摘Oncovirus infection is crucial in human malignancies.Certain oncoviruses can lead to structural variations in the human genome known as viral genomic integration,which can contribute to tumorigenesis.Existing viral integration detection tools differ in their underlying algorithms pinpointing different aspects or features of viral integration phenomenon.We discuss about major procedures in performing viral integration detection.More importantly,we provide a technical update on Virus-Clip to facilitate its usage on the latest human genome builds(hg19 and hg38)and the adoption of multi-thread mode for faster initial read alignment.By comparing the execution of Virus-Clip using single-thread and multi-thread modes of read alignment on targeted-panel sequencing data of HBV-associated hepatocellular carcinoma patients,we demonstrate the marked improvement of multi-thread mode in terms of significantly reduced execution time,while there is negligible difference in memory usage.Taken together,with the current update of Virus-Clip,it will continue supporting the in silico detection of oncoviral integration for better understanding of various human malignancies.
文摘针对面向整个全基因组关联研究(genome-wide association studies,GWAS)未覆盖基因组区的数据集成问题,提出基于自训练的半监督机器学习实现的语意映射技术应用于该研究领域的方法。研究结果表明:该方法能有效实现对整个GWAS未覆盖基因组区的自动的语意映射,精度达到94.2%,召回率达到97.5%,能有效降低对人类专家的依赖程度,实现对整个GWAS未覆盖基因组区数据的快捷有效集成。
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).
文摘Asthma,a chronic respiratory disease with a global prevalence of approximately 300 million individuals,presents a significant societal and economic burden.This multifaceted syndrome exhibits diverse clinical phenotypes and pathogenic endotypes influenced by various factors.The advent of omics technologies has revolutionized asthma research by delving into the molecular foundation of the disease to unravel its underlying mechanisms.Omics technologies are employed to systematically screen for potential biomarkers,encompassing genes,transcripts,methylation sites,proteins,and even the microbiome components.This review provides an insightful overview of omics applications in asthma research,with a special emphasis on genetics,transcriptomics,epigenomics,and the microbiome.We explore the cutting-edge methods,discoveries,challenges,and potential future directions in the realm of asthma omics research.By integrating multi-omics and non-omics data through advanced sta-tistical techniques,we aspire to advance precision medicine in asthma,guiding diagnosis,risk assessment,and personalized treatment strategies for this heterogeneous condition.
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Microarray and deep sequencing technologies have provided unprecedented opportunities for mapping genome mutations,RNA transcripts,transcription factor binding,and histone modifications at high resolution at the genome-wide level.This has revolutionized the way in which transcriptomes,regulatory networks and epigenetic regulations have been studied and large amounts of heterogeneous data have been generated.Although efforts are being made to integrate these datasets unbiasedly and efficiently,how best to do this still remains a challenge.Here we review major impacts of high-throughput genome-wide data generation,their relevance to human diseases,and various bioinformatics approaches for data integration.Finally,we provide a case study on inflammatory diseases.
