Genetic factors play an important role in the etiology of inflammatory bowel disease(IBD). The launch of genome-wide association study(GWAS) represents a landmark in the genetic study of human complex disease. Concurr...Genetic factors play an important role in the etiology of inflammatory bowel disease(IBD). The launch of genome-wide association study(GWAS) represents a landmark in the genetic study of human complex disease. Concurrently, computational methods have undergone rapid development during the past a few years, which led to the identification of numerous disease susceptibility loci. IBD is one of the successful examples of GWAS and related analyses. A total of 163 genetic loci and multiple signaling pathways have been identified to be associated with IBD. Pleiotropic effects were found for many of these loci; and risk prediction models were built based on a broad spectrum of genetic variants. Important gene-gene, gene-environment interactions and key contributions of gut microbiome are being discovered. Here we will review the different types of analyses that have been applied to IBD genetic study, discuss the computational methods for each type of analysis, and summarize the discoveries made in IBD research with the application of these methods.展开更多
Salvia miltiorrhiza (Chinese, Danshen) is one of the most famous traditional herbs, and has been used to treat cardiovascular disease. Despite the wide application of Danshen in China, the mechanisms of its bioactive ...Salvia miltiorrhiza (Chinese, Danshen) is one of the most famous traditional herbs, and has been used to treat cardiovascular disease. Despite the wide application of Danshen in China, the mechanisms of its bioactive components are poorly understood. The present study used bioinformatics to identify possible mechanisms by which Danshen treats cardiovascular disease. Possible human protein targets of Danshen were identified in the PubChem database, possible human gene targets of cardiovascular disease were identified in the NCBI database, and then both sets of targets were analyzed using Ingenuity Pathway Analysis to predict molecular networks affected by Danshen in cardiovascular disease. The results suggest that signaling proteins affected by Danshen in cardiovascular disease, which include FASN, PAFAH1B2, PLA2G7, PAFAH1B3 and IL1B, are involved primarily in LXR/RXR activation, atherosclerosis signaling, hepatic fibrosis/hepatic stellate cell activation, acute phase response signaling. The main networks affected by Danshen are predicted to involve in cellular movement, immune cell trafficking, hematological system development and function;DNA replication, recombination, and repair, cancer, hematological disease;cardiovascular disease, organismal injury and abnormalities, tissue morphology.These results identify several specific proteins and pathways that may be affected by Danshen in cardiovascular disease, and they illustrate the power of integrative bioinformatics and chemical fragment analysis for focusing mechanistic studies.展开更多
The global dissemination of H5 avian influenza viruses represents a significant threat to both human and animal health.In thisstudy,we conducted a genome-wide siRNA library screening against the highly pathogenic H5N1 i...The global dissemination of H5 avian influenza viruses represents a significant threat to both human and animal health.In thisstudy,we conducted a genome-wide siRNA library screening against the highly pathogenic H5N1 influenza virus,leading us tothe identification of 457 cellular cofactors(441 proviral factors and 16 antiviral factors)involved in the virus replication cycle.Gene Ontology term enrichment analysis revealed that the candidate gene data sets were enriched in gene categoriesassociated with mRNA splicing via spliceosome in the biological process,integral component of membrane in the cellularcomponent,and protein binding in the molecular function.Reactome pathway analysis showed that the immune system(up to63 genes)was the highest enriched pathway.Subsequent comparisons with four previous siRNA library screenings revealedthat the overlapping rates of the involved pathways were 8.53%-62.61%,which were significantly higher than those of thecommon genes(1.85%-6.24%).Together,our genome-wide siRNA library screening unveiled a panorama of host cellularnetworks engaged in the regulation of highly pathogenic H5N1 influenza virus replication,which may provide potential targetsand strategies for developing novel antiviral countermeasures.展开更多
文摘Genetic factors play an important role in the etiology of inflammatory bowel disease(IBD). The launch of genome-wide association study(GWAS) represents a landmark in the genetic study of human complex disease. Concurrently, computational methods have undergone rapid development during the past a few years, which led to the identification of numerous disease susceptibility loci. IBD is one of the successful examples of GWAS and related analyses. A total of 163 genetic loci and multiple signaling pathways have been identified to be associated with IBD. Pleiotropic effects were found for many of these loci; and risk prediction models were built based on a broad spectrum of genetic variants. Important gene-gene, gene-environment interactions and key contributions of gut microbiome are being discovered. Here we will review the different types of analyses that have been applied to IBD genetic study, discuss the computational methods for each type of analysis, and summarize the discoveries made in IBD research with the application of these methods.
基金Supported by National Natural Science Foundation of China (grant NO. U1804179)Henan Science and Technology Innovation Team, Investigation on Plant Resources in Dabie Mountains and the study and utilization of active components of special plants (grant NO. 2017083)Nanhu Scholars Program for Young Scholars of Xinyang Normal University (grant NO. 2018001).
文摘Salvia miltiorrhiza (Chinese, Danshen) is one of the most famous traditional herbs, and has been used to treat cardiovascular disease. Despite the wide application of Danshen in China, the mechanisms of its bioactive components are poorly understood. The present study used bioinformatics to identify possible mechanisms by which Danshen treats cardiovascular disease. Possible human protein targets of Danshen were identified in the PubChem database, possible human gene targets of cardiovascular disease were identified in the NCBI database, and then both sets of targets were analyzed using Ingenuity Pathway Analysis to predict molecular networks affected by Danshen in cardiovascular disease. The results suggest that signaling proteins affected by Danshen in cardiovascular disease, which include FASN, PAFAH1B2, PLA2G7, PAFAH1B3 and IL1B, are involved primarily in LXR/RXR activation, atherosclerosis signaling, hepatic fibrosis/hepatic stellate cell activation, acute phase response signaling. The main networks affected by Danshen are predicted to involve in cellular movement, immune cell trafficking, hematological system development and function;DNA replication, recombination, and repair, cancer, hematological disease;cardiovascular disease, organismal injury and abnormalities, tissue morphology.These results identify several specific proteins and pathways that may be affected by Danshen in cardiovascular disease, and they illustrate the power of integrative bioinformatics and chemical fragment analysis for focusing mechanistic studies.
基金supported by the National Key Research and DevelopmentProgram of China(2021YFD1800203 and 2021YFD1800204)the National Natural Science Foundation of China(NSFC)(32192453,32272979,and 32172847)+2 种基金the China PostdoctoralScience Foundation(2019M660897)the Innovation Program ofChinese Academy of Agricultural Sciences(CAAS-CSLPDCP-202401)the Earmarked Fund for China Agriculture Re-search System(CARS-41-G12)。
文摘The global dissemination of H5 avian influenza viruses represents a significant threat to both human and animal health.In thisstudy,we conducted a genome-wide siRNA library screening against the highly pathogenic H5N1 influenza virus,leading us tothe identification of 457 cellular cofactors(441 proviral factors and 16 antiviral factors)involved in the virus replication cycle.Gene Ontology term enrichment analysis revealed that the candidate gene data sets were enriched in gene categoriesassociated with mRNA splicing via spliceosome in the biological process,integral component of membrane in the cellularcomponent,and protein binding in the molecular function.Reactome pathway analysis showed that the immune system(up to63 genes)was the highest enriched pathway.Subsequent comparisons with four previous siRNA library screenings revealedthat the overlapping rates of the involved pathways were 8.53%-62.61%,which were significantly higher than those of thecommon genes(1.85%-6.24%).Together,our genome-wide siRNA library screening unveiled a panorama of host cellularnetworks engaged in the regulation of highly pathogenic H5N1 influenza virus replication,which may provide potential targetsand strategies for developing novel antiviral countermeasures.
