Dearlove Bethany L, Frost Simon D W
Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
PLoS Comput Biol. 2015 Jul 6;11(7):e1004312. doi: 10.1371/journal.pcbi.1004312. eCollection 2015 Jul.
Previous work has shown that asymmetry in viral phylogenies may be indicative of heterogeneity in transmission, for example due to acute HIV infection or the presence of 'core groups' with higher contact rates. Hence, evidence of asymmetry may provide clues to underlying population structure, even when direct information on, for example, stage of infection or contact rates, are missing. However, current tests of phylogenetic asymmetry (a) suffer from false positives when the tips of the phylogeny are sampled at different times and (b) only test for global asymmetry, and hence suffer from false negatives when asymmetry is localised to part of a phylogeny. We present a simple permutation-based approach for testing for asymmetry in a phylogeny, where we compare the observed phylogeny with random phylogenies with the same sampling and coalescence times, to reduce the false positive rate. We also demonstrate how profiles of measures of asymmetry calculated over a range of evolutionary times in the phylogeny can be used to identify local asymmetry. In combination with different metrics of asymmetry, this combined approach offers detailed insights of how phylogenies reconstructed from real viral datasets may deviate from the simplistic assumptions of commonly used coalescent and birth-death process models.
先前的研究表明，病毒系统发育中的不对称性可能表明传播存在异质性，例如由于急性HIV感染或存在接触率较高的“核心群体”。因此，即使缺少关于感染阶段或接触率等直接信息，不对称性的证据也可能为潜在的人群结构提供线索。然而，当前的系统发育不对称性测试：（a）当系统发育的末端在不同时间进行采样时会出现假阳性；（b）仅测试全局不对称性，因此当不对称性局限于系统发育的一部分时会出现假阴性。我们提出了一种基于简单排列的方法来测试系统发育中的不对称性，即我们将观察到的系统发育与具有相同采样和合并时间的随机系统发育进行比较，以降低假阳性率。我们还展示了如何利用在系统发育的一系列进化时间上计算的不对称性度量的概况来识别局部不对称性。结合不同的不对称性度量，这种组合方法提供了详细的见解，说明从真实病毒数据集重建的系统发育可能如何偏离常用的合并和生灭过程模型的简单假设。
