Centre for Doctoral Training in Mathematics for Real-World Systems, University of Warwick, Coventry CV47AL, UK.
Healthcare Associated Infections and Antimicrobial Resistance Division, National Infection Service, Public Health England, London NW95EQ, UK.
Syst Biol. 2022 Aug 10;71(5):1073-1087. doi: 10.1093/sysbio/syab095.
Microbial population genetics models often assume that all lineages are constrained by the same population size dynamics over time. However, many neutral and selective events can invalidate this assumption and can contribute to the clonal expansion of a specific lineage relative to the rest of the population. Such differential phylodynamic properties between lineages result in asymmetries and imbalances in phylogenetic trees that are sometimes described informally but which are difficult to analyze formally. To this end, we developed a model of how clonal expansions occur and affect the branching patterns of a phylogeny. We show how the parameters of this model can be inferred from a given dated phylogeny using Bayesian statistics, which allows us to assess the probability that one or more clonal expansion events occurred. For each putative clonal expansion event, we estimate its date of emergence and subsequent phylodynamic trajectory, including its long-term evolutionary potential which is important to determine how much effort should be placed on specific control measures. We demonstrate the applicability of our methodology on simulated and real data sets. Inference under our clonal expansion model can reveal important features in the evolution and epidemiology of infectious disease pathogens. [Clonal expansion; genomic epidemiology; microbial population genomics; phylodynamics.].
微生物种群遗传学模型通常假设所有谱系在随时间推移的种群大小动态方面受到相同的限制。然而,许多中性和选择性事件可以否定这一假设,并有助于特定谱系相对于种群其余部分的克隆扩张。谱系之间这种不同的系统发育动态特性导致系统发育树中的不对称和不平衡,这些有时是非正式描述的,但很难进行正式分析。为此,我们开发了一种模型,用于说明克隆扩张如何发生以及如何影响系统发育树的分支模式。我们展示了如何使用贝叶斯统计从给定的已标记系统发育树中推断该模型的参数,这使我们能够评估一个或多个克隆扩张事件发生的概率。对于每个假定的克隆扩张事件,我们估计其出现的日期和随后的系统发育轨迹,包括其长期进化潜力,这对于确定应该在特定控制措施上投入多少努力非常重要。我们在模拟和真实数据集上展示了我们方法的适用性。在我们的克隆扩张模型下进行推断,可以揭示传染病病原体进化和流行病学中的重要特征。[克隆扩张;基因组流行病学;微生物种群基因组学;系统发育动力学。]