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A sparse hierarchical Bayesian model for detecting relevant antigenic sites in virus evolution

机译:一种稀疏的等级贝叶斯模型,用于检测病毒演化中的相关抗原位点

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摘要

Understanding how viruses offer protection against closely related emerging strains is vital for creating effective vaccines. For many viruses, multiple serotypes often co-circulate and testing large numbers of vaccines can be infeasible. Therefore the development of an in silico predictor of cross-protection between strains is important to help optimise vaccine choice. Here we present a sparse hierarchical Bayesian model for detecting relevant antigenic sites in virus evolution (SABRE) which can account for the experimental variability in the data and predict antigenic variability. The method uses spike and slab priors to identify sites in the viral protein which are important for the neutralisation of the virus. Using the SABRE method we are able to identify a number of key antigenic sites within several viruses, as well as providing estimates of significant changes in the evolutionary history of the serotypes. We show how our method outperforms alternative established methods; standard mixed effects models, the mixed effects LASSO, and the mixed effects elastic nets. We also propose novel proposal mechanisms for the Markov chain Monte Carlo simulations, which improve mixing and convergence over that of the established component-wise Gibbs sampler.
机译:了解病毒如何提供针对紧密相关的新兴病毒株的保护对于创建有效疫苗至关重要。对于许多病毒,经常会同时传播多种血清型,因此无法测试大量疫苗。因此,菌株间交叉保护的计算机预测因子的发展对于帮助优化疫苗选择很重要。在这里,我们提出了一种稀疏的分层贝叶斯模型,用于检测病毒进化中的相关抗原位点(SABRE),该模型可以解释数据中的实验变异性并预测抗原变异性。该方法使用刺突和平板先验来鉴定病毒蛋白中对病毒中和重要的位点。使用SABRE方法,我们能够识别几种病毒中的许多关键抗原位点,并提供血清型进化史上重大变化的估计值。我们展示了我们的方法如何胜过其他已建立的方法。标准混合效果模型,混合效果LASSO和混合效果弹性网。我们还为马尔可夫链蒙特卡罗模拟提出了新颖的提议机制,该机制比已建立的逐分量吉布斯采样器提高了混合和收敛性。

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