The first step in the analysis of high-throughput experiment results is often to identify genes orproteins with certain characteristics, such as genes being differentially expressed (DE). To gainmore insights into the...The first step in the analysis of high-throughput experiment results is often to identify genes orproteins with certain characteristics, such as genes being differentially expressed (DE). To gainmore insights into the underlying biology, functional enrichment analysis is then conductedto provide functional interpretation for the identified genes or proteins. The hypergeometricP value has been widely used to investigate whether genes from predefined functional terms,e.g., Reactome, are enriched in the DE genes. The hypergeometric P value has several limitations: (1) computed independently for each term, thus neglecting biological dependence;(2) subject to a size constraint that leads to the tendency of selecting less-specific terms. In this paper,a Bayesian approach is proposed to overcome these limitations by incorporating the interconnected dependence structure of biological functions in the Reactome database through a CARprior in a Bayesian hierarchical logistic model. The inference on functional enrichment is thenbased on posterior probabilities that are immune to the size constraint. This method can detectmoderate but consistent enrichment signals and identify sets of closely related and biologicallymeaningful functional terms rather than isolated terms. The performance of the Bayesian methodis demonstrated via a simulation study and a real data application.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
基金This work has been supported in part by National Institutes of Health(NIH)[grant number 1R15HG006365-01]National Science Foundation(NSF)[grant number IIS-1302564].
文摘The first step in the analysis of high-throughput experiment results is often to identify genes orproteins with certain characteristics, such as genes being differentially expressed (DE). To gainmore insights into the underlying biology, functional enrichment analysis is then conductedto provide functional interpretation for the identified genes or proteins. The hypergeometricP value has been widely used to investigate whether genes from predefined functional terms,e.g., Reactome, are enriched in the DE genes. The hypergeometric P value has several limitations: (1) computed independently for each term, thus neglecting biological dependence;(2) subject to a size constraint that leads to the tendency of selecting less-specific terms. In this paper,a Bayesian approach is proposed to overcome these limitations by incorporating the interconnected dependence structure of biological functions in the Reactome database through a CARprior in a Bayesian hierarchical logistic model. The inference on functional enrichment is thenbased on posterior probabilities that are immune to the size constraint. This method can detectmoderate but consistent enrichment signals and identify sets of closely related and biologicallymeaningful functional terms rather than isolated terms. The performance of the Bayesian methodis demonstrated via a simulation study and a real data application.
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.
