Gill Mandev S, Lemey Philippe, Bennett Shannon N, Biek Roman, Suchard Marc A
Department of Statistics, Columbia University, New York, NY 10027, USA.
Department of Microbiology and Immunology, Rega Institute, KU Leuven, Minderbroederstaat 10, 3000 Leuven, Belgium.
Syst Biol. 2016 Nov;65(6):1041-1056. doi: 10.1093/sysbio/syw050. Epub 2016 Jul 1.
Effective population size characterizes the genetic variability in a population and is a parameter of paramount importance in population genetics and evolutionary biology. Kingman's coalescent process enables inference of past population dynamics directly from molecular sequence data, and researchers have developed a number of flexible coalescent-based models for Bayesian nonparametric estimation of the effective population size as a function of time. Major goals of demographic reconstruction include identifying driving factors of effective population size, and understanding the association between the effective population size and such factors. Building upon Bayesian nonparametric coalescent-based approaches, we introduce a flexible framework that incorporates time-varying covariates that exploit Gaussian Markov random fields to achieve temporal smoothing of effective population size trajectories. To approximate the posterior distribution, we adapt efficient Markov chain Monte Carlo algorithms designed for highly structured Gaussian models. Incorporating covariates into the demographic inference framework enables the modeling of associations between the effective population size and covariates while accounting for uncertainty in population histories. Furthermore, it can lead to more precise estimates of population dynamics. We apply our model to four examples. We reconstruct the demographic history of raccoon rabies in North America and find a significant association with the spatiotemporal spread of the outbreak. Next, we examine the effective population size trajectory of the DENV-4 virus in Puerto Rico along with viral isolate count data and find similar cyclic patterns. We compare the population history of the HIV-1 CRF02_AG clade in Cameroon with HIV incidence and prevalence data and find that the effective population size is more reflective of incidence rate. Finally, we explore the hypothesis that the population dynamics of musk ox during the Late Quaternary period were related to climate change. [Coalescent; effective population size; Gaussian Markov random fields; phylodynamics; phylogenetics; population genetics.
有效种群大小表征了一个种群中的遗传变异性，并且是种群遗传学和进化生物学中至关重要的一个参数。金曼的溯祖过程使得能够直接从分子序列数据推断过去的种群动态，并且研究人员已经开发了许多灵活的基于溯祖的模型，用于对有效种群大小作为时间函数的贝叶斯非参数估计。种群统计学重建的主要目标包括识别有效种群大小的驱动因素，以及理解有效种群大小与这些因素之间的关联。在基于贝叶斯非参数溯祖方法的基础上，我们引入了一个灵活的框架，该框架纳入了随时间变化的协变量，利用高斯马尔可夫随机场来实现有效种群大小轨迹的时间平滑。为了近似后验分布，我们采用了为高度结构化高斯模型设计的高效马尔可夫链蒙特卡罗算法。将协变量纳入种群统计学推断框架能够在考虑种群历史不确定性的同时，对有效种群大小与协变量之间的关联进行建模。此外，它可以导致对种群动态的更精确估计。我们将我们的模型应用于四个例子。我们重建了北美浣熊狂犬病的种群统计学历史，并发现与疫情的时空传播存在显著关联。接下来，我们结合病毒分离株计数数据研究了波多黎各登革热病毒4型（DENV-4）的有效种群大小轨迹，并发现了类似的周期性模式。我们将喀麦隆HIV-1 CRF02_AG分支的种群历史与HIV发病率和流行率数据进行比较，发现有效种群大小更能反映发病率。最后，我们探讨了晚第四纪时期麝牛的种群动态与气候变化相关的假说。[溯祖；有效种群大小；高斯马尔可夫随机场；系统发育动力学；系统发育学；种群遗传学。
