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Radial Basis Function Approximations of Bayesian Parameter Posterior Densities for Uncertainty Analysis

机译:不确定性分析的贝叶斯参数后验密度的径向基函数逼近

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Dynamical models are widely used in systems biology to describe biological processes ranging from single cell transcription of genes to the tissue scale formation of gradients for cell guidance. One of the key issues for this class of models is the estimation of kinetic parameters from given measurement data, the so called parameter estimation. Measurement noise and the limited amount of data, give rise to uncertainty in estimates which can be captured in a probability density over the parameter space. Unfortunately, studying this probability density, using e.g. Markov chain Monte-Carlo, is often computationally demanding as it requires the repeated simulation of the underlying model. In the case of highly complex models, such as PDE models, this can render the study intractable. In this paper, we will present novel methods for analysis of such probability densities using networks of radial basis functions. We employed lattice generation algorithms, adaptive interacting particle sampling schemes as well as classical sampling schemes for the generation of approximation nodes coupled to the respective weighting scheme and compared their efficiency on different application examples. Our analysis showed that the novel method can yield an expected L_2 approximation error in marginals that is several orders of magnitude lower compared to classical approximations. This allows for a drastic reduction of the number of model evaluations. This facilitates the analysis of uncertainty for problems with high computational complexity. Finally, we successfully applied our method to a complex partial differential equation model for guided cell migration of dendritic cells.
机译:动力学模型被广泛用于系统生物学中,以描述从基因的单细胞转录到组织指导梯度的组织规模形成的生物学过程。此类模型的关键问题之一是根据给定的测量数据估算动力学参数,即所谓的参数估算。测量噪声和有限的数据量导致估计中的不确定性,这些不确定性可以在参数空间上的概率密度中捕获。不幸的是,使用马尔可夫链蒙特卡洛经常需要计算,因为它需要对基础模型进行重复仿真。在高度复杂的模型(例如PDE模型)的情况下,这会使研究变得棘手。在本文中,我们将介绍使用径向基函数网络分析此类概率密度的新颖方法。我们采用晶格生成算法,自适应交互粒子采样方案以及经典采样方案来生成与各个加权方案耦合的近似节点,并在不同的应用实例上比较了它们的效率。我们的分析表明,与经典近似方法相比,该新方法可以在边际中产生预期的L_2近似误差,该误差要低几个数量级。这样可以大大减少模型评估的数量。这有助于分析具有高计算复杂性的问题的不确定性。最后,我们成功地将我们的方法应用于树突状细胞的指导细胞迁​​移的复杂偏微分方程模型。

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