Host and Microbial Genetic Determinants of Febrile Illness in West Africa

描述（由申请人提供）：该提案旨在调查西非发热性疾病的宿主和微生物基因组决定因素，并建立西非基因组研究（WAGER）网络，该网络由位于尼日利亚、塞拉利昂和塞内加尔的西非法语和英语卓越中心组成。这三个国家的合作伙伴在相互之间以及与布罗德研究所、哈佛大学和杜兰大学的美国合作伙伴在研究拉沙热和恶性疟原虫疟疾等毁灭性疾病方面有着长期的成功合作记录。此外，我们在能力建设和培训非洲科学家方面进行了大量投资。我们认识到，为了真正参与这场基因组学革命，非洲研究人员必须具备能力，不仅能够开展大规模基因组学项目，而且能够自始至终开展完全独立的研究项目。非洲的发热性疾病对非洲大陆来说是一个毁灭性的负担，其研究是一个大规模联合项目和小型实地研究都可以产生重大影响的地方。在这一提议中，我们将大力加强培训和支持非洲健康领域尖端基因组学研究的努力。我们将在Broad Institute和WAGER站点开展年度严格培训，并将其发展为可供所有H3 Africa合作伙伴使用的更大的培训计划。我们将在救世主大学建立一个核心基因组学中心，配备Illumina MiSeq，并为每年从三个WAGER现场收集750份高质量的发热患者样本奠定基础。有了这些基础，我们将使用现场部署和最先进的基因组技术来识别驱动发热性疾病的病原体，并检查传染病易感性的遗传基础。我们将通过四个项目来实现这一目标，其中两个项目侧重于可现场部署的基因组诊断，并可在当地开展。这些项目是：（1）通过现场诊断确定不明原因发热的微生物;（2）通过微生物宏基因组学确定不明原因发热的特征;（3）检查LF和疟疾的人类遗传决定因素;（4）通过全基因组关联确定LF的人类遗传决定因素。

DESCRIPTION (provided by applicant): This proposal aims to investigate host and microbial genomic determinants of febrile illness in West Africa and establish the West African GEnomic Research (WAGER) Network, consisting of West African Francophone and Anglophone centers of excellence in Nigeria, Sierra-Leone and Senegal. The partners in these three countries have a long-term track record of successful collaboration with each other and with US partners at the Broad Institute, Harvard University, and Tulane University studying the devastating diseases Lassa fever (LF) and Plasmodium falciparum malaria. Moreover, we have a demonstrated deep investment in capacity building and training of African scientists. We recognize that in order to truly participate in this genomic revolution, African researchers must be equipped not only to enable large-scale genomics projects, but also to carry out fully independent research projects, from beginning to end. Febrile illness in Africa is a devastating burden to the continent, and its study is a place in which both large-scale consortium projects and small field studies can have a major impact. In this proposal we will greatly enhance efforts for training and supporting cutting-edge genomics research on health in Africa. We will carry our annual rigorous trainings at the Broad Institute and at WAGER sites and develop them into a larger training program that can be used by all H3Africa partners. We will create a core genomics center at Redeemer's University with an lllumina MiSeq and lay the groundwork to collect 750 high quality samples from febrile patient per year from each of the three WAGER field sites. With these foundations in place, we will use both field-deployed and state-of-the-art genomic technology to identify pathogens driving febrile illness and to examine the genetic basis of infectious disease susceptibility. We will do this through four projects two of which are focused on field-deployable genomic diagnostics and can be carried out at the local sites. The projects are (1) Identifying Microbes Underlying Fever of Unknown Origin (FUO) Through Field Diagnostics; (2) Characterizing FUO through Microbial Metagenomics; (3) Examining Human Genetic Determinants of LF and Malaria; and (4) Identifying Human Genetic Determinants of LF Through Genome-Wide Association.