Exploiting Viral Genomics to Understand Disease

利用病毒基因组学来了解疾病

• 批准号: 8831594
• 负责人: Suman Ranjan Das
• 金额: $ 289.5万
• 依托单位: J. CRAIG VENTER INSTITUTE, INC.
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8831594
• 关键词: Algorithms; Animal Viruses; Animals; Antiviral Agents; Antiviral resistance; Bioinformatics; Bioterrorism; Communicable Diseases; Communities; Data; Data Set; Disease; Disease Outbreaks; Epidemic; Evolution; Family; Genetic Recombination; Genetic Variation; Genome; Genomic approach; Genomics; Human; Human Virus; Immune response; Institutes; National Institute of Allergy and Infectious Disease; Pathogenesis; Phylogenetic Analysis; Public Health; Research Project Grants; Sequence Analysis; Vaccines; Viral; Viral Pathogenesis; Virus; Virus Diseases; deep sequencing; genome sequencing; metagenomic sequencing; microbiome; next generation sequencing; novel; pandemic disease; pandemic preparedness; pathogen; response; transcriptomics; transmission process

Research' Project 1 focuses on significant endemic viral pathogens from humans and viruses from animal hosts that have strong zoonotic potential. High-throughput whole-genome next-generation sequencing (NGS), combined with bioinformatics algorithms, will be used to sequence and analyze the genomes from more than 10,000 strains representing seven viral species. This will characterize the genetic diversity over a range of virus families, including many NIAID priority pathogens, to understand critical evolutionary mechanisms central to viral evolution, pathogenesis, transmission, and/or antiviral resistance. Specifically we aim to: 1) compare and contrast the genetic diversity and evolutionary dynamics of viruses circulating within and/or between humans and animal reservoirs, 2) elucidate viral-host-microbiome determinants that influence viral pathogenesis, and 3) perform deep sequencing to understand intra-host viral diversity, transmission dynamics, and antiviral resistance. Collectively, this project will use multiple genomics approaches (e.g., genomic sequencing, metagenomics, and transcriptomics) to provide the scientific community with genomic data sets of broad use from important viral families. These data will be analyzed using phylogenetics and other bioinformatics algorithms to show the spatial and temporal evolution of these pathogens. Finally, the data generated will identify, track, and predict antigenic drift/shift, recombination, escape from natural or vaccine-induced host immune responses, antiviral resistance, inter- and intra-species transmission, and the response of a host's commensal microbiota to viral infection. The information generated from these studies will help us to produce superior vaccines and antivirals, and the data sets will prove critical for rapid responses to the emergence of novel pathogens (i.e., pandemic preparedness) that arise naturally or as a result of bioterrorism.

研究'项目1的重点是人类和动物病毒的重要特有病毒病原体 具有强大人畜共患潜力的宿主。高通量全基因组下一代测序 （NGS）结合生物信息学算法，将用于对基因组进行测序和分析。 超过10,000个代表7种病毒物种的菌株。这将表征一个遗传多样性 病毒家族范围，包括许多NIAID优先病原体，以了解关键进化 机制是病毒进化，发病机理，传播和/或抗病毒抗性的中心。特别是我们 目的是：1）比较和对比循环的病毒的遗传多样性和进化动力学 和/或人类和动物储层之间，2）阐明病毒宿主 - 菌菌群决定因素 影响病毒发病机理，3）进行深度测序以了解宿主内病毒多样性， 传输动力学和抗病毒抗性。 总的来说，该项目将使用多种基因组学方法（例如，基因组测序，宏基因组学， 和转录组学）为科学界提供了重要的基因组数据集 病毒家庭。这些数据将使用系统发育学和其他生物信息学算法进行分析，以显示 这些病原体的空间和时间演变。最后，生成的数据将识别，跟踪和 预测抗原漂移/移位，重组，从天然或疫苗诱导的宿主免疫反应中逃脱， 抗病毒抗性，种间和种内传播以及宿主共生的响应 微生物群至病毒感染。这些研究产生的信息将有助于我们产生优越的 疫苗和抗病毒药物以及数据集将证明对快速反应新颖的出现至关重要 病原体（即大流行的准备）自然或由于生物恐怖主义而产生。