The Geography of Avian Influenza Evolution: Spatial and Temporal Relationships Between Virus Genes and Human-Environment Factors

流感病毒造成了巨大的经济损失，对公共卫生构成了巨大的挑战。基因重组和重组产生的大流行毒株可能会在未来造成重大灾难。在20世纪，三次流感大流行在短暂的暴发期间导致数百万人死亡。亚洲最近出现的H5N1禽流感人间病例提醒公共卫生工作者、政策制定者和全体民众注意在不久的将来出现新的流感大流行的可能性。这项研究项目将使用计算遗传学和地理学方法来建立一个公共的、空间上参考的禽流感病毒(AIV)基因数据库，并将调查人类-环境因素与AIV进化之间的关系。研究人员的具体目标是(1)利用流感病毒的基因组序列数据对其进行基因分型，(2)构建公共流感基因-地理数据库(IGGD)，(3)分析人类环境生态因素对流感病毒进化的影响。该项目将系统地描述流感病毒基因型的空间和时间模式，并加强对流感病毒进化的生态系统驱动因素的基本了解。研究人员将使用来自国家生物技术信息中心和洛斯阿拉莫斯国家实验室的流感基因组测序数据。该项目的分析将集中在H5N1禽流感。该项目的第一阶段将涉及开发一种新的流感基因分型算法，该算法将在公共基因数据库中进一步对H5N1禽流感病毒进行分类。该基因分型算法将通过避免多个序列比对和构建系统发育树来对AIV进行基因分型。新的基因类型将由每个病毒片段的聚类指数确定。这一阶段的成果包括流感基因分型算法和与每个AIV分离株相关的基因分型。第二阶段将涉及开发公共IGGD，以存储和管理流感病毒基因信息和相关的人类环境生态系统因素。IGGD将是第一个此类时空流感基因数据库。它将包括被假设与AIV进化相关的基因信息以及生态系统因素。该数据库Web服务器不仅将为大流行毒株预测提供重要资源，而且将为未来的医学地理和分子流行病学分析提供重要资源。最后一阶段将分析人类-环境生态系统因素对禽流感病毒进化的影响，包括气候、鸟类迁徙模式、人口分布、耕作系统、农业产出以及土地利用和土地覆盖参数。该项目将使用常规统计方法和建立生态位模型来分析AIV基因和生态系统变量之间的关系。该项目将开发工具来研究AIV的进化及其相关的生态系统因素。这项工作的最终目标是加强对流感病毒进化的人类-环境生态系统驱动因素的基本了解。大多数医学地理研究都是在人群层面上进行的，但这项研究将包括从区域层面的环境数据到分子层面的遗传信息。影响流感进化的因素还没有得到很好的理解，因为之前的研究没有同时考虑人类和环境生态系统因素。这项研究将同时对它们进行调查。

The influenza virus has been responsible for large economic losses and is a great public health challenge. Pandemic strains that emerge from genetic reassortment and recombination may cause a major disaster in the future. During the 20th century, three influenza pandemics killed millions of people during short outbreak periods. Recent human cases of H5N1 avian influenza in Asia have alerted public health workers, policy makers, and the population as a whole to the possibility of the emergence of a new influenza pandemic in the near future. This research project will use computational genetics and geographic approaches to build a public, spatially referenced avian influenza virus (AIV) genotype database and will investigate relationships between human-environment factors and AIV evolution. The investigators' specific objectives are (1) to classify influenza viral genotypes using their genomic sequence data, (2) to construct a public Influenza Genotype-Geographic Database (IGGD), and (3) to analyze the impacts of human-environment ecosystem factors on influenza viral evolution. This project will generate a systematic description of the spatial and temporal patterns of influenza viral genotypes and enhance basic understanding of ecosystem drivers of influenza viral evolution. The investigators will use influenza genome sequencing data from the National Center for Biotechnology Information and the Los Alamos National Laboratory. The analysis in this project will focus on H5N1 AIV. The first phase of the project will involve development of a new influenza genotyping algorithm that will further categorize H5N1 AIVs within a public genotype database. This proposed genotyping algorithm will categorize the genotypes of AIVs by avoiding multiple sequence alignment and phylogeny tree construction. The new genotypes will be determined by the cluster index for each segment of each virus. The deliverables for this phase include an influenza genotyping algorithm and genotype associated with each AIV isolate. The second phase will involve developing the public IGGD to store and manage the influenza viral genotype information and associated human-environment ecosystem factors. The IGGD will be the first spatial-temporal influenza genotype database of its kind. It will include genotype information as well as the ecosystems factors that have been hypothesized to be related to AIV evolution. This database web server will provide an important resource for not only pandemic strain prediction but also future medical geography and molecular epidemiological analysis. The last phase will analyze the impacts of human-environment ecosystem factors on AIV evolution, including climate, bird migration patterns, human population distributions, farming systems, agricultural output, and land-use and land-cover parameters. Relationships between the AIV genotype and the ecosystems variables will be analyzed using both a conventional statistics and by building ecological niche models.The project will develop tools to study AIV evolution and the ecosystems factors in which it is associated. The ultimate goal of this effort is to enhance basic understanding of human-environment ecosystem drivers of influenza viral evolution. Most medical geographic studies are conducted at the population level, but this study will include scales from regional-level environmental data to molecular-level genetic information. The factors that influence the evolution of influenza are not well understood because previous studies have not jointly looked at both human and environmental ecosystem factors. This study will investigate them simultaneously.