Viral deep-sequencing data play a crucial role toward understanding disease transmission network flows, because the higher resolution of these data compared to standard Sanger sequencing provide evidence into the direction of infectious disease transmission. To more fully utilize these rich data and account for the uncertainties in phylogenetic analysis outcomes, we propose a spatial Poisson process model to uncover HIV transmission flow patterns at the population level. We represent pairings of two individuals with viral sequence data as typed points, with coordinates representing covariates such as gender and age, and the point type representing the unobserved transmission statuses (linkage and direction). Points are associated with observed scores on the strength of evidence for each transmission status that are obtained through standard deep-sequenece phylogenetic analysis. Our method is able to jointly infer the latent transmission statuses for all pairings and the transmission flow surface on the source-recipient covariate space. In contrast to existing methods, our framework does not require pre-classification of the transmission statuses of data points, instead learning them probabilistically through a fully Bayesian inference scheme. By directly modeling continuous spatial processes with smooth densities, our method enjoys significant computational advantages compared to previous methods that rely on discretization of the covariate space. We demonstrate that our framework can capture age structures in HIV transmission at high resolution, and bring valuable insights in a case study on viral deep-sequencing data from Southern Uganda.
翻译:与标准Sanger测序相比,这些数据的更高分辨率为传染性疾病传播方向提供了证据。为了更充分地利用这些丰富的数据,并解释植物遗传分析结果的不确定性,我们提议了一个空间Poisson进程模型,以发现人口一级的艾滋病毒传播流模式。我们代表两个个人与病毒序列数据相配的打字点,其坐标代表的是诸如性别和年龄等共变式数据,以及代表未观测的传播状态(链接和方向)的点类型。点与通过标准的深序列血压分析获得的每一种传播状态的证据强度的观测得分有关。我们的方法能够共同推导出所有配对的潜在传播状态和源源源源-源端采集变异空间的传输流表面。与现有方法不同,我们的框架不需要预先分解数据传输状态,而不需要通过完全Bayes推断状态(链接和方向),而是与观察到的证据强度得分相关。我们的方法可以直接地模拟我们以往的甚深层数据传输结构的精确度,从而展示了我们以往的甚高分辨率分析方法。