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，该网络由西非法语和英语中心组成，这些中心位于尼日利亚，塞拉利昂和塞内加尔。这三个国家的合作伙伴在相互合作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破坏性疾病拉沙热和恶性疟原虫疟疾方面有着长期成功的合作记录。此外，我们在非洲科学家的能力建设和培训方面进行了深度投资。我们认识到，为了真正参与这场基因组学革命，非洲研究人员不仅必须具备大规模基因组学项目的能力，而且必须具备从头到尾完全独立开展研究项目的能力。非洲的发热性疾病对该大陆来说是一个毁灭性的负担，对它的研究是一个大型联合项目和小型实地研究都能产生重大影响的地方。在这项建议中，我们将大大加强培训和支持非洲卫生方面的尖端基因组学研究的努力。我们将在博德研究所和WAGER站点开展年度严格培训，并将其发展成一个更大的培训项目，供所有h3非洲合作伙伴使用。我们将在Redeemer's University建立一个核心基因组学中心，使用lllumina MiSeq，并为每年从三个WAGER现场站点收集750个高质量的发热患者样本奠定基础。有了这些基础，我们将使用实地部署的和最先进的基因组技术来确定导致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做到这一点，其中两个项目侧重于可在现场部署的基因组诊断，并可在当地地点进行。项目包括：(1)通过现场诊断鉴定不明原因发热（FUO）的微生物；(2)微生物宏基因组学表征FUO；(3)研究LF和疟疾的人类遗传决定因素；(4)通过全基因组关联鉴定人类LF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.