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Parameter estimation with bio-inspired meta-heuristic optimization: modeling the dynamics of endocytosis

机译:基于生物启发式元启发式优化的参数估计:对内吞作用的动力学建模

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Background We address the task of parameter estimation in models of the dynamics of biological systems based on ordinary differential equations (ODEs) from measured data, where the models are typically non-linear and have many parameters, the measurements are imperfect due to noise, and the studied system can often be only partially observed. A representative task is to estimate the parameters in a model of the dynamics of endocytosis, i.e., endosome maturation, reflected in a cut-out switch transition between the Rab5 and Rab7 domain protein concentrations, from experimental measurements of these concentrations. The general parameter estimation task and the specific instance considered here are challenging optimization problems, calling for the use of advanced meta-heuristic optimization methods, such as evolutionary or swarm-based methods. Results We apply three global-search meta-heuristic algorithms for numerical optimization, i.e., differential ant-stigmergy algorithm (DASA), particle-swarm optimization (PSO), and differential evolution (DE), as well as a local-search derivative-based algorithm 717 (A717) to the task of estimating parameters in ODEs. We evaluate their performance on the considered representative task along a number of metrics, including the quality of reconstructing the system output and the complete dynamics, as well as the speed of convergence, both on real-experimental data and on artificial pseudo-experimental data with varying amounts of noise. We compare the four optimization methods under a range of observation scenarios, where data of different completeness and accuracy of interpretation are given as input. Conclusions Overall, the global meta-heuristic methods (DASA, PSO, and DE) clearly and significantly outperform the local derivative-based method (A717). Among the three meta-heuristics, differential evolution (DE) performs best in terms of the objective function, i.e., reconstructing the output, and in terms of convergence. These results hold for both real and artificial data, for all observability scenarios considered, and for all amounts of noise added to the artificial data. In sum, the meta-heuristic methods considered are suitable for estimating the parameters in the ODE model of the dynamics of endocytosis under a range of conditions: With the model and conditions being representative of parameter estimation tasks in ODE models of biochemical systems, our results clearly highlight the promise of bio-inspired meta-heuristic methods for parameter estimation in dynamic system models within system biology.
机译:背景技术我们根据测量数据中的常微分方程(ODE)处理生物系统动力学模型中参数估计的任务,其中模型通常是非线性的,并且具有许多参数,由于噪声,测量不完美,并且所研究的系统通常只能部分观察。代表性的任务是从这些浓度的实验测量值估计Rab5和Rab7结构域蛋白浓度之间的切出转换过渡中反映的内吞作用动力学模型,即内体成熟,中的参数。此处考虑的一般参数估计任务和特定实例是具有挑战性的优化问题,要求使用高级的元启发式优化方法,例如进化或基于群体的方法。结果我们应用了三种全局搜索元启发式算法进行数值优化,即差分蚂蚁算法(DASA),粒子群优化(PSO)和差分进化(DE),以及局部搜索导数-基于算法717(A717)的ODE估计参数的任务。我们通过许多指标评估它们在考虑的代表性任务上的性能,包括重建系统输出的质量和完整的动力学特性以及收敛速度,包括真实实验数据和人工伪实验数据,包括变化的噪声量。我们比较了一系列观察方案下的四种优化方法,其中给出了不同完整性和解释准确性的数据作为输入。结论总体而言,全局元启发式方法(DASA,PSO和DE)明显优于本地基于导数的方法(A717)。在这三种元启发式方法中,就目标函数(即重构输出)和收敛性而言,差分进化(DE)表现最佳。这些结果适用于真实数据和人工数据,考虑的所有可观察性场景以及添加到人工数据中的所有噪声量。总之,所考虑的元启发式方法适用于在一系列条件下估计ODE模型中内吞动力学的参数:由于该模型和条件代表生化系统ODE模型中参数估计任务清楚地强调了系统生物学内动态系统模型中用于参数估计的生物启发式元启发式方法的前景。

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