Vaughan Timothy G, Stadler Tanja
Department of Biosystems Science and Engineering, ETH Zurich, Klingelbergstrasse 48, Basel 4056, Switzerland.
Computational Evolution Group, Swiss Institute of Bioinformatics, Quartier Sorge - Bâtiment Amphipôle, Lausanne 1015, Switzerland.
Mol Biol Evol. 2025 Jun 4;42(6). doi: 10.1093/molbev/msaf130.
Phylodynamic methods provide a coherent framework for the inference of population parameters directly from genetic data. They are an important tool for understanding both the spread of epidemics as well as long-term macroevolutionary trends in speciation and extinction. In particular, phylodynamic methods based on multitype birth-death models have been used to infer the evolution of discrete traits, the movement of individuals or pathogens between geographic locations or host types, and the transition of infected individuals between disease stages. In these models, population heterogeneity is treated by assigning individuals to different discrete types. Typically, methods which allow inference of parameters under multitype birth-death models integrate over the possible birth-death trajectories (i.e. the type-specific population size functions) to reduce the computational demands of the inference. As a result, it has not been possible to use these methods to directly infer the dynamics of trait-specific population sizes, infected host counts or other such demographic quantities. In this article, we present a method which infers these multitype trajectories with minimal additional computational cost beyond that of existing methods. We demonstrate the practicality of our approach by applying it to a previously published set of Middle East respiratory syndrome coronavirus genomes, inferring the numbers of human and camel cases through time, together with the number and timing of spillovers from the camel reservoir. This application highlights the multitype population trajectory's ability to elucidate properties of the population which are not directly ancestral to its sampled members.
系统发育动力学方法为直接从基因数据推断种群参数提供了一个连贯的框架。它们是理解流行病传播以及物种形成和灭绝的长期宏观进化趋势的重要工具。特别是,基于多类型出生-死亡模型的系统发育动力学方法已被用于推断离散性状的进化、个体或病原体在地理位置或宿主类型之间的移动,以及感染个体在疾病阶段之间的转变。在这些模型中,通过将个体分配到不同的离散类型来处理种群异质性。通常,允许在多类型出生-死亡模型下推断参数的方法会对可能的出生-死亡轨迹(即特定类型的种群大小函数)进行积分,以降低推断的计算需求。因此,一直无法使用这些方法直接推断特定性状的种群大小、感染宿主数量或其他此类人口统计数量的动态。在本文中,我们提出了一种方法,该方法以比现有方法仅增加最小额外计算成本的方式推断这些多类型轨迹。我们通过将其应用于一组先前发表的中东呼吸综合征冠状病毒基因组,展示了我们方法的实用性,推断出随时间变化的人类和骆驼病例数,以及从骆驼宿主溢出的数量和时间。此应用突出了多类型种群轨迹阐明其抽样成员并非直接祖先的种群属性的能力。