Department of Epidemiology, University of Michigan, Ann Arbor, Michigan 48109, USA.
Genetics. 2009 Dec;183(4):1421-30. doi: 10.1534/genetics.109.106021. Epub 2009 Sep 21.
We present a formalism for unifying the inference of population size from genetic sequences and mathematical models of infectious disease in populations. Virus phylogenies have been used in many recent studies to infer properties of epidemics. These approaches rely on coalescent models that may not be appropriate for infectious diseases. We account for phylogenetic patterns of viruses in susceptible-infected (SI), susceptible-infected-susceptible (SIS), and susceptible-infected-recovered (SIR) models of infectious disease, and our approach may be a viable alternative to demographic models used to reconstruct epidemic dynamics. The method allows epidemiological parameters, such as the reproductive number, to be estimated directly from viral sequence data. We also describe patterns of phylogenetic clustering that are often construed as arising from a short chain of transmissions. Our model reproduces the moments of the distribution of phylogenetic cluster sizes and may therefore serve as a null hypothesis for cluster sizes under simple epidemiological models. We examine a small cross-sectional sample of human immunodeficiency (HIV)-1 sequences collected in the United States and compare our results to standard estimates of effective population size. Estimated prevalence is consistent with estimates of effective population size and the known history of the HIV epidemic. While our model accurately estimates prevalence during exponential growth, we find that periods of decline are harder to identify.
我们提出了一种形式主义,用于将遗传序列推断种群规模和人口中传染病的数学模型统一起来。病毒系统发育已经在许多最近的研究中用于推断流行病的特性。这些方法依赖于可能不适用于传染病的合并模型。我们解释了易感感染(SI)、易感感染易感(SIS)和易感感染恢复(SIR)传染病模型中病毒的系统发育模式,我们的方法可能是用于重建流行病动力学的人口统计学模型的可行替代方法。该方法允许直接从病毒序列数据估计传染病参数,如繁殖数。我们还描述了经常被认为是由短链传播引起的系统发育聚类模式。我们的模型再现了系统发育聚类大小分布的矩,因此可以作为简单传染病模型下聚类大小的零假设。我们检查了在美国收集的一小部分人类免疫缺陷病毒(HIV)-1 序列的横截面样本,并将我们的结果与有效种群规模的标准估计进行了比较。估计的流行率与有效种群规模的估计和 HIV 流行的已知历史一致。虽然我们的模型可以准确估计指数增长期间的流行率,但我们发现下降期更难识别。