Utilize Microbial Metagenomics for Viral Pathogen Characterization

项目摘要-项目1 最近的突发公共卫生事件，最引人注目的是2014-2016年的埃博拉疫情，暴露了 西非卫生系统的脆弱性和改善全球卫生系统的迫切需要 监测传染病威胁。尽管这一地区存在传染病的负担， 人们对西非传播的微生物，特别是病毒的了解很少。 这在一定程度上是由于在许多地区缺乏检测已知病原体的诊断能力， 以及由许多这些微生物引起的非特异性症状，使得临床很难 确定感染的原因。在这方面，基因组方法，包括下一代 测序，最近已经成为病原体检测和发现的强大工具，如 并使人们能够有价值地了解这些病毒的起源、传播和生物学特性 病原体。在这个项目中，我们建议使用尖端的下一代测序能力 在西非三个合作中心建立，以识别已知和新病毒 在发烧的患者和健康对照中。我们将使用计算方法来组装 完整的病毒基因组，并了解该病毒的进化动力学和种群遗传学 通过元基因组测序确定的最重要的病毒威胁。最后，我们将 采用新的工具来提高病原体测序的效率和灵敏度。 该项目将为强大的测序的可持续应用建立一个框架 公共卫生背景下的技术，并确定该地区最紧迫的病毒威胁， 为项目2中相关诊断测试的开发提供信息。此外， 三个西非国家，我们合作中心的排序努力将产生广泛的 对广泛地理区域的病毒的洞察，并允许共享 在整个西非加强生物监测的方法。这不仅将继续 推进西非传染病基因组学研究，将提供立竿见影、可操作的 对保护当地社区和防止未来疫情爆发的见解。

Project Summary – Project 1 Recent public health emergencies, most notably the 2014-2016 Ebola epidemic, have exposed the vulnerabilities in West African health systems and the urgent need for improved global surveillance of infectious disease threats. Despite the burden of infectious disease in this region, the spectrum of circulating microbes, especially viruses, in West Africa is poorly understood. This owes, in part, to the lack of diagnostic capacity to detect known pathogens in many areas, and the nonspecific symptoms caused by many of these microbes, making it difficult to clinically determine the cause of infection. In this context, genomic approaches, including next-generation sequencing, have recently emerged as powerful tools for pathogen detection and discovery, as well as enabling valuable insight into the origins, transmission and biological properties of these pathogens. In this Project, we propose to use cutting edge next-generation sequencing capacity established at the three West African Collaborative Centers to identify known and novel viruses in patients with a fever and healthy controls. We will use computational approaches to assemble full viral genomes and understand the evolutionary dynamics and population genetics of the most important viral threats identified through metagenomic sequencing. Lastly, we will implement novel tools to enhance the efficiency and sensitivity of pathogen sequencing. This project will establish a framework for the sustainable application of powerful sequencing technologies in public health contexts and identify the most pressing viral threats in this region, informing the development of relevant diagnostic tests in Project 2. Furthermore, working across three West African countries, the sequencing efforts of our collaborative center will yield broad insights into the virome across a wide geographic region and allow for the sharing of approaches to enhance biosurveillance across West Africa. Not only will this continue to advance the genomics of infectious disease in West Africa, it will provide immediate, actionable insights to protect local communities and prevent future outbreaks.