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系统发育学中的贝叶斯非参数聚类:流感病毒抗原进化建模

Bayesian nonparametric clustering in phylogenetics: modeling antigenic evolution in influenza.

作者信息

Cybis Gabriela B, Sinsheimer Janet S, Bedford Trevor, Rambaut Andrew, Lemey Philippe, Suchard Marc A

机构信息

Department of Statistics, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.

Department of Biomathematics, David Geffen School of Medicine at UCLA, Los Angeles, California, U.S.A.

出版信息

Stat Med. 2018 Jan 30;37(2):195-206. doi: 10.1002/sim.7196. Epub 2017 Jan 18.

Abstract

Influenza is responsible for up to 500,000 deaths every year, and antigenic variability represents much of its epidemiological burden. To visualize antigenic differences across many viral strains, antigenic cartography methods use multidimensional scaling on binding assay data to map influenza antigenicity onto a low-dimensional space. Analysis of such assay data ideally leads to natural clustering of influenza strains of similar antigenicity that correlate with sequence evolution. To understand the dynamics of these antigenic groups, we present a framework that jointly models genetic and antigenic evolution by combining multidimensional scaling of binding assay data, Bayesian phylogenetic machinery and nonparametric clustering methods. We propose a phylogenetic Chinese restaurant process that extends the current process to incorporate the phylogenetic dependency structure between strains in the modeling of antigenic clusters. With this method, we are able to use the genetic information to better understand the evolution of antigenicity throughout epidemics, as shown in applications of this model to H1N1 influenza. Copyright © 2017 John Wiley & Sons, Ltd.

摘要

流感每年导致多达50万人死亡,抗原变异性是其流行病学负担的主要部分。为了直观呈现众多病毒株之间的抗原差异,抗原绘图方法利用结合试验数据进行多维缩放,将流感抗原性映射到低维空间。对这类试验数据的分析理论上会使具有相似抗原性的流感毒株自然聚类,且这些聚类与序列进化相关。为了理解这些抗原组的动态变化,我们提出了一个框架,通过结合结合试验数据的多维缩放、贝叶斯系统发育机制和非参数聚类方法,对遗传进化和抗原进化进行联合建模。我们提出了一种系统发育中餐厅过程,将当前过程进行扩展,以便在抗原簇建模中纳入毒株之间的系统发育依赖结构。通过这种方法,我们能够利用遗传信息更好地理解整个疫情期间抗原性的演变,如该模型在H1N1流感中的应用所示。版权所有© 2017约翰·威利父子有限公司。

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