Pathogen Population Genomics and Evolution

前言：随着病原体基因特别是全基因组序列数据的日益丰富， 迫切需要分析工具和创新方法来利用它们。特别是， 利用基因组数据推断传播链和病原菌进化的方法 通过宿主免疫、疫苗和抗生素进行选择仍处于初级阶段。这些问题是 从根本上不同于每次检查一个序列时提出的问题类型，即 阐明感染和发病机制中保守的生物学方面。人口基因组研究减少 关于病原体的种群异质性、其后果和原因。这些推论自然而然 致力于传输动态模型的参数估计，甚至更多 从根本上说，到确定应该如何构建这样的模型，以及测试它们的 预测。到目前为止，使用MIDAS和非MIDAS资金进行分析工作，使用非MIDAS资金用于 测序的成本，在过去的五年里，我们使用病原体取得了许多重大发现 种群基因组学和遗传学，我们已经确定了许多改进和扩展方法的机会 在接下来的五年里，以及将现有的方法应用于生物学和 流行病学。

Introduction: With increasing availability of pathogen genetic and especially whole-genome sequence data, there is a pressing need for analytical tools and innovative approaches to make use of them. In particular, methods for using genomic data to make inferences about transmission chains and pathogen evolution under selection by host immunity, vaccines, and antibiotics, are still in their infancy. These questions are fundamentally different from the types of questions asked when examining one sequence at a time, which illuminate the biology of conserved aspects of infection and pathogenesis. Population genomic studies shed light on population heterogeneity in the pathogen, its consequences and causes. These inferences naturally lend themselves to the estimation of parameters for transmission-dynamic models and, even more fundamentally, to the determination of how such models should be structured, and the testing of their predictions. To date, using MIDAS and non-MIDAS funding for analytic efforts, and non-MIDAS funding for the costs of sequencing, we have made a number of significant discoveries over the last five years using pathogen population genomics and genetics, and we have identified many opportunities to improve and expand methods over the next five years, as well as to apply existing methods to significant questions of biology and epidemiology.