论文标题
基于高斯过程的全球灵敏度分析,用于复杂的生物力学问题
Global sensitivity analysis based on Gaussian-process metamodelling for complex biomechanical problems
论文作者
论文摘要
生物力学模型通常需要描述非常复杂的系统,器官或疾病,因此还包括大量参数。基于物理的模型的吸引人特征之一是,在这些模型(大多数)中,参数具有明确的物理含义。然而,这些参数的确定通常非常精心且昂贵,并且在人群中显示出很大的散布。因此,必须确定当前特定问题的最重要参数。为了区分对特定模型输出与非影响参数有重大影响的参数,我们使用灵敏度分析,特别是SOBOL方法作为基于全局方差的方法。但是,SOBOL方法需要大量的模型评估,这对于计算昂贵的模型而言是令人难以置信的。因此,我们将高斯工艺用作基础完整模型的元模型。 Metamodelling引入了进一步的不确定性,我们也对此进行了量化。我们通过将其应用于两个不同的问题来证明该方法:纳米颗粒介导的多相肿瘤增长模型中的药物递送以及动脉生长和重塑。即使是相对较少的完整模型评估,也足以确定两种情况下的影响参数,并将其与非影响参数分开。该方法还允许定量高阶相互作用效应。因此,我们表明,基于方差的全局灵敏度分析对于计算昂贵的生物力学模型是可行的。灵敏度分析的不同方面涵盖了估计过程中涉及的不确定性的透明声明。这样的全球灵敏度分析不仅有助于大大降低参数实验确定的成本,而且对这种复杂模型的反向分析也非常有益。
Biomechanical models often need to describe very complex systems, organs or diseases, and hence also include a large number of parameters. One of the attractive features of physics-based models is that in those models (most) parameters have a clear physical meaning. Nevertheless, the determination of these parameters is often very elaborate and costly and shows a large scatter within the population. Hence, it is essential to identify the most important parameter for a particular problem at hand. In order to distinguish parameters which have a significant influence on a specific model output from non-influential parameters, we use sensitivity analysis, in particular the Sobol method as a global variance-based method. However, the Sobol method requires a large number of model evaluations, which is prohibitive for computationally expensive models. We therefore employ Gaussian processes as a metamodel for the underlying full model. Metamodelling introduces further uncertainty, which we also quantify. We demonstrate the approach by applying it to two different problems: nanoparticle-mediated drug delivery in a multiphase tumour-growth model, and arterial growth and remodelling. Even relatively small numbers of evaluations of the full model suffice to identify the influential parameters in both cases and to separate them from non-influential parameters. The approach also allows the quantification of higher-order interaction effects. We thus show that a variance-based global sensitivity analysis is feasible for computationally expensive biomechanical models. Different aspects of sensitivity analysis are covered including a transparent declaration of the uncertainties involved in the estimation process. Such a global sensitivity analysis not only helps to massively reduce costs for experimental determination of parameters but is also highly beneficial for inverse analysis of such complex models.