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动态网络的系统发育。

Phylogenies from dynamic networks.

机构信息

Dept of Electronic Engineering and Computer Science, Queen Mary University of London, London, United Kingdom.

Dept of Mathematics, Imperial College London, London, United Kingdom.

出版信息

PLoS Comput Biol. 2019 Feb 26;15(2):e1006761. doi: 10.1371/journal.pcbi.1006761. eCollection 2019 Feb.

Abstract

The relationship between the underlying contact network over which a pathogen spreads and the pathogen phylogenetic trees that are obtained presents an opportunity to use sequence data to learn about contact networks that are difficult to study empirically. However, this relationship is not explicitly known and is usually studied in simulations, often with the simplifying assumption that the contact network is static in time, though human contact networks are dynamic. We simulate pathogen phylogenetic trees on dynamic Erdős-Renyi random networks and on two dynamic networks with skewed degree distribution, of which one is additionally clustered. We use tree shape features to explore how adding dynamics changes the relationships between the overall network structure and phylogenies. Our tree features include the number of small substructures (cherries, pitchforks) in the trees, measures of tree imbalance (Sackin index, Colless index), features derived from network science (diameter, closeness), as well as features using the internal branch lengths from the tip to the root. Using principal component analysis we find that the network dynamics influence the shapes of phylogenies, as does the network type. We also compare dynamic and time-integrated static networks. We find, in particular, that static network models like the widely used Barabasi-Albert model can be poor approximations for dynamic networks. We explore the effects of mis-specifying the network on the performance of classifiers trained identify the transmission rate (using supervised learning methods). We find that both mis-specification of the underlying network and its parameters (mean degree, turnover rate) have a strong adverse effect on the ability to estimate the transmission parameter. We illustrate these results by classifying HIV trees with a classifier that we trained on simulated trees from different networks, infection rates and turnover rates. Our results point to the importance of correctly estimating and modelling contact networks with dynamics when using phylodynamic tools to estimate epidemiological parameters.

摘要

病原体传播的基础接触网络与获得的病原体系统发育树之间的关系为利用序列数据了解难以通过经验研究的接触网络提供了机会。然而,这种关系并不明确,通常在模拟中进行研究,通常假设接触网络在时间上是静态的,尽管人类接触网络是动态的。我们在动态 Erdős-Renyi 随机网络和两个具有倾斜度分布的动态网络上模拟病原体系统发育树,其中一个网络还具有聚类。我们使用树形状特征来探索添加动态性如何改变总体网络结构和系统发育之间的关系。我们的树特征包括树中小结构(樱桃,叉头)的数量,树不平衡的度量(Sackin 指数,Colless 指数),来自网络科学的特征(直径,接近度)以及使用从尖端到根的内部分支长度的特征。使用主成分分析,我们发现网络动态影响系统发育的形状,网络类型也是如此。我们还比较了动态和时间综合静态网络。我们发现,特别是像广泛使用的 Barabasi-Albert 模型这样的静态网络模型可能是动态网络的较差近似。我们探讨了错误指定网络对用于识别传播率的分类器性能的影响(使用监督学习方法)。我们发现,错误指定基础网络及其参数(平均度数,周转率)都会对估计传播参数的能力产生强烈的不利影响。我们通过使用针对来自不同网络,感染率和周转率的模拟树进行训练的分类器对 HIV 树进行分类,来说明这些结果。我们的结果表明,在使用系统发育动力学工具估计流行病学参数时,正确估计和建模具有动态的接触网络非常重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1f60/6420041/aed150903d00/pcbi.1006761.g001.jpg

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