论文标题
具有随机参数的微分方程模型的有效推理和可识别性分析
Efficient inference and identifiability analysis for differential equation models with random parameters
论文作者
论文摘要
异质性是许多生物过程行为的主要因素。尽管如此,数学和统计分析忽略生物异质性作为实验数据的可变性来源很常见。因此,通过模型参数中的可变性明确合并异质性的模型的可识别性的方法相对欠发达。我们基于力矩匹配,开发了一个新的基于可能性的框架,用于对微分方程模型的推理和识别性分析,该模型通过根据概率分布而变化的参数捕获生物异质性。由于我们的新方法基于近似似然函数,因此它具有高度的灵活性。我们使用基于轮廓可能性的常见方法和基于马尔可夫链蒙特卡洛的贝叶斯方法来证明可识别性分析。通过三个案例研究,我们通过提供与独立观察到的数据有关模型参数的统计矩相关的高参数的推理和识别性分析来证明我们的方法。我们的方法具有与忽略异质性的模型的分析相当的计算成本,对许多现有替代方案有了重大改进。我们证明了随机参数模型的分析如何有助于从生物学数据中更好地理解异质性的来源。
Heterogeneity is a dominant factor in the behaviour of many biological processes. Despite this, it is common for mathematical and statistical analyses to ignore biological heterogeneity as a source of variability in experimental data. Therefore, methods for exploring the identifiability of models that explicitly incorporate heterogeneity through variability in model parameters are relatively underdeveloped. We develop a new likelihood-based framework, based on moment matching, for inference and identifiability analysis of differential equation models that capture biological heterogeneity through parameters that vary according to probability distributions. As our novel method is based on an approximate likelihood function, it is highly flexible; we demonstrate identifiability analysis using both a frequentist approach based on profile likelihood, and a Bayesian approach based on Markov-chain Monte Carlo. Through three case studies, we demonstrate our method by providing a didactic guide to inference and identifiability analysis of hyperparameters that relate to the statistical moments of model parameters from independent observed data. Our approach has a computational cost comparable to analysis of models that neglect heterogeneity, a significant improvement over many existing alternatives. We demonstrate how analysis of random parameter models can aid better understanding of the sources of heterogeneity from biological data.