Enhancing dengue virus genomic surveillance to uncover circulating genetic diversity

加强登革热病毒基因组监测以揭示循环遗传多样性

• 批准号: 10471494
• 负责人: Nathan Dale Grubaugh
• 金额: $ 150.75万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-21 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10471494
• 关键词: 2019-nCoV; Address; Cancer Surveillance Research Program; Caribbean region; Classification; Complex; County; Dengue; Dengue Virus; Development; Disease; Disease Outbreaks; Epidemiology; Evolution; Future; Genetic Variation; Genomics; Genotype; Goals; Knowledge; Measures; Modernization; Pattern; Phylogenetic Analysis; Process; Protocols documentation; Public Health; Research; Research Personnel; Serotyping; System; Training; Travel; Variant; Virus; data tools; genome sequencing; genomic data; innovation; interest; pathogen; programs; underserved area; variants of concern; viral genomics; virus genetics; whole genome

Project Summary New solutions are desperately needed to reduce the annual global burden of dengue. As we are currently witnessing for SARS-CoV-2, virus genomics can be harnessed to directly inform public health control measures. For most other pathogens, including dengue virus, we do not have the depth of genomic information for these uses. For dengue virus, part of the issue is its complexity: it is comprised of four genetically distinct serotypes with many defined genotypes and even more undefined variants. Furthermore, our current surveillance and research programs are not set up to fully take advantage of virus genomics. In this proposal, I will address the major barriers for modernizing dengue virus genomic programs: (1) development of a universal-dengue virus whole genome sequencing approach utilizing the framework being established globally for SARS-CoV-2; (2) formation of a collaborative network in the underserved region of the Caribbean to uncover the circulating dengue virus diversity and provide local training and sequencing support; (3) utilization of travel surveillance to provide information from beyond the network to serve as a template for other genomic surveillance systems; (4) development of a new dengue virus genetic classification system to more easily identify variants of concern/interest and to better utilize the genomic data without needing complex phylogenetic analysis; (5) creation of a webtool to provide easy access to the variant classification system, detailed regional and county-level analysis, genomic data, and protocols; and (6) detailed phylogenetic analysis to uncover key epidemiological processes, like the outbreak emergence interval and patterns of spread, to aid in future disease forecasting. Completion of the goals outlined in this proposal would significantly advance our knowledge and assessment of dengue virus diversity, evolution, and epidemiology. Researchers will be able to capitalize on these data and tools to facilitate the innovation of genomics-informed control strategies.

项目摘要 迫切需要新的解决方案来减少登革热的年度全球负担。正如我们目前 作为SARS-CoV-2的见证，病毒基因组学可以直接用于公共卫生控制 措施对于大多数其他病原体，包括登革热病毒，我们没有深入的基因组研究， 这些用途的信息。对于登革热病毒，问题的一部分在于它的复杂性：它由四个 具有许多确定的基因型和甚至更多未确定的变体的遗传上不同的血清型。此外，委员会认为， 我们目前的监测和研究计划并没有充分利用病毒基因组学。在 在这一建议中，我将解决登革热病毒基因组计划现代化的主要障碍：（1） 开发通用登革热病毒全基因组测序方法， （2）在服务不足的地区建立合作网络， * 在加勒比地区发现流行的登革热病毒多样性，并提供当地培训和测序支助; (3)利用旅行监测提供网络以外的信息，作为模板， 其他基因组监测系统;（4）开发新的登革热病毒基因分类系统， 更容易地识别关注/感兴趣的变体，并且更好地利用基因组数据，而不需要 复杂的系统发育分析;（5）创建一个网络工具，以提供对变异分类的方便访问 系统，详细的区域和县级分析，基因组数据和协议;以及（6）详细的 系统发育分析，以揭示关键的流行病学过程，如疫情出现间隔， 传播模式，以帮助未来的疾病预测。完成本提案中概述的目标 将大大提高我们对登革热病毒多样性、进化和 流行病学研究人员将能够利用这些数据和工具来促进创新， 基于基因组学的控制策略。

项目成果

Toward a global virus genomic surveillance network.

• DOI: 10.1016/j.chom.2023.03.003
• 发表时间: 2023-06-14
• 期刊: CELL HOST & MICROBE
• 影响因子: 30.3
• 作者: Hill, Verity;Githinji, George;Vogels, Chantal B. F.;Bento, Ana I.;Chaguza, Chrispin;Carrington, Christine V. F.;Grubaugh, Nathan D.
• 通讯作者: Grubaugh, Nathan D.