Temporal signal and the phylodynamic threshold of SARS-CoV-2
Temporal signal and the phylodynamic threshold of SARS-CoV-2
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DOI：
10.1093/ve/veaa061
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发表时间：
2020-07-01
期刊：
影响因子：
5.3
通讯作者：
Baele, Guy
中科院分区：
文献类型：
--
作者：
Duchene, Sebastian;Featherstone, Leo;Baele, Guy
正在进行的 SARS-CoV-2 爆发标志着首次近乎实时地生成并公开了大量基因组序列数据。对这些数据的早期分析显示序列变异较低，这一发现与最近出现的疫情爆发一致，但这提出了一个问题：这些数据对于进化速率和时间尺度的系统发育推断是否具有足够的信息。系统动力学阈值是一个关键概念，指的是可用基因组样本中积累了足够的分子进化变化以获得可靠的系统动力学估计的时间点。例如，在达到系统动力学阈值之前，基因组变异非常低，即使大量的基因组序列也可能不足以估计病毒的进化速度和爆发的时间范围。我们从公共数据库中收集了八个不同时间点的 SARS-CoV-2 基因组序列，并对时间信号进行了一系列测试，以确定是否以及何时达到系统动力学阈值，以及可以从这些数据中可靠得出的推论范围。我们的结果表明，到 2020 年 2 月 2 日，进化速率和时间尺度的估计已成为可能。对后续数据集（包括 47 至 122 个基因组）的分析以约 1.1 x 10(-3) 子/位点/年的进化速率收敛，起源时间约为 2019 年 11 月下旬。我们的研究提供了评估系统动力学阈值的指南，并表明建立此阈值是了解疫情基因组监测中早期数据的力量和局限性的基本步骤。
The ongoing SARS-CoV-2 outbreak marks the first time that large amounts of genome sequence data have been generated and made publicly available in near real time. Early analyses of these data revealed low sequence variation, a finding that is consistent with a recently emerging outbreak, but which raises the question of whether such data are sufficiently informative for phylogenetic inferences of evolutionary rates and time scales. The phylodynamic threshold is a key concept that refers to the point in time at which sufficient molecular evolutionary change has accumulated in available genome samples to obtain robust phylodynamic estimates. For example, before the phylodynamic threshold is reached, genomic variation is so low that even large amounts of genome sequences may be insufficient to estimate the virus's evolutionary rate and the time scale of an outbreak. We collected genome sequences of SARS-CoV-2 from public databases at eight different points in time and conducted a range of tests of temporal signal to determine if and when the phylodynamic threshold was reached, and the range of inferences that could be reliably drawn from these data. Our results indicate that by 2 February 2020, estimates of evolutionary rates and time scales had become possible. Analyses of subsequent data sets, that included between 47 and 122 genomes, converged at an evolutionary rate of about 1.1 x 10(-3) subs/site/year and a time of origin of around late November 2019. Our study provides guidelines to assess the phylodynamic threshold and demonstrates that establishing this threshold constitutes a fundamental step for understanding the power and limitations of early data in outbreak genome surveillance.