Measuring asymmetry in time-stamped phylogenies

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 ...过往研究表明，病毒系统发育树（viral phylogeny）的不对称性或可反映传播过程的异质性，例如由急性HIV感染，或是接触率更高的‘核心群体’所引发的传播异质性。因此，即便缺乏感染阶段或接触率等直接观测信息，不对称性的相关证据仍可为解析种群潜在结构提供重要线索。然而，当前的系统发育不对称性检测方法存在两类局限：其一，当系统发育树的末梢样本采样时间不同时，会出现假阳性结果；其二，仅能检测全局不对称性，因此当不对称性仅局限于系统发育树的某一部分时，会出现假阴性结果。本研究提出一种简单的基于置换的系统发育不对称性检测方法：通过将观测得到的系统发育树，与采样时间和溯祖时间（coalescence time）均一致的随机生成系统发育树进行比对，以降低假阳性发生率。本研究同时展示了，针对一系列进化时间尺度计算得到的不对称性度量谱……