Dybowski Richard, McKinley Trevelyan J, Mastroeni Pietro, Restif Olivier
Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom.
PLoS One. 2013 Dec 20;8(12):e82317. doi: 10.1371/journal.pone.0082317. eCollection 2013.
Understanding the mechanisms underlying the observed dynamics of complex biological systems requires the statistical assessment and comparison of multiple alternative models. Although this has traditionally been done using maximum likelihood-based methods such as Akaike's Information Criterion (AIC), Bayesian methods have gained in popularity because they provide more informative output in the form of posterior probability distributions. However, comparison between multiple models in a Bayesian framework is made difficult by the computational cost of numerical integration over large parameter spaces. A new, efficient method for the computation of posterior probabilities has recently been proposed and applied to complex problems from the physical sciences. Here we demonstrate how nested sampling can be used for inference and model comparison in biological sciences. We present a reanalysis of data from experimental infection of mice with Salmonella enterica showing the distribution of bacteria in liver cells. In addition to confirming the main finding of the original analysis, which relied on AIC, our approach provides: (a) integration across the parameter space, (b) estimation of the posterior parameter distributions (with visualisations of parameter correlations), and (c) estimation of the posterior predictive distributions for goodness-of-fit assessments of the models. The goodness-of-fit results suggest that alternative mechanistic models and a relaxation of the quasi-stationary assumption should be considered.
要理解复杂生物系统中观察到的动态背后的机制,需要对多个替代模型进行统计评估和比较。虽然传统上是使用基于最大似然的方法,如赤池信息准则(AIC)来完成这项工作,但贝叶斯方法越来越受欢迎,因为它们以后验概率分布的形式提供了更多信息丰富的输出。然而,在贝叶斯框架中,对多个模型进行比较因在大参数空间上进行数值积分的计算成本而变得困难。最近提出了一种新的、高效的计算后验概率的方法,并将其应用于物理科学中的复杂问题。在这里,我们展示了如何将嵌套采样用于生物科学中的推理和模型比较。我们对小鼠感染肠炎沙门氏菌的实验数据进行了重新分析,展示了细菌在肝细胞中的分布。除了证实依赖AIC的原始分析的主要发现外,我们的方法还提供了:(a)跨参数空间的积分,(b)后验参数分布的估计(以及参数相关性的可视化),以及(c)用于模型拟合优度评估的后验预测分布的估计。拟合优度结果表明,应考虑替代的机制模型和放宽准平稳假设。