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A novel cost function for parameters estimation in oscillatory biochemical systems

机译:振荡生化系统中参数估计的新型成本函数

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Oscillatory pathways are among the most important classes of biochemical systems with examples ranging from circadian rhythms and cell cycle maintenance. Mathematical modeling of these highly interconnected biochemical networks is needed to meet numerous objectives such as investigating, predicting and controlling the dynamics of these systems. Identifying the kinetic rate parameters is essential for fully modeling these and other biological processes. These kinetic parameters, however, cannot be measured directly and most of them have to be estimated using parameter fitting techniques. One of the issues with estimating kinetic parameters in oscillatory systems is the irregularities in the Least Square (LS) cost function surface used to estimate these parameters, which is caused by the periodicity of the measurements. These irregularities result in numerous local minima, which limit the performance of even some of the most robust global optimization algorithms. We proposed a cost function to address these issues by integrating temporal information with periodic information embedded in the measurements. This new cost function has better surface properties leading to fewer local minima and better performance of global optimization algorithms. We verified for two oscillatory biochemical systems that our method results in an increased ability to estimate accurate kinetic parameters as compared to the traditional LS cost function. This will eventually lead to biochemical models that are more precise, predictable and controllable.
机译:振荡途径是生化系统中最重要的类别,其例子包括昼夜节律和细胞周期维持。需要对这些高度互连的生化网络进行数学建模,以实现许多目标,例如研究,预测和控制这些系统的动力学。鉴定动力学速率参数对于完全模拟这些和其他生物过程至关重要。但是,这些动力学参数无法直接测量,其中大多数必须使用参数拟合技术进行估算。估计振荡系统中动力学参数的问题之一是用于估计这些参数的最小二乘(LS)成本函数曲面中的不规则性,这是由测量的周期性引起的。这些不规则性导致许多局部最小值,甚至限制了某些最可靠的全局优化算法的性能。我们提出了一种成本函数,通过将时间信息与测量中嵌入的周期性信息相集成来解决这些问题。这个新的成本函数具有更好的表面特性,从而导致更少的局部最小值和更好的全局优化算法性能。我们验证了两个振荡生化系统,与传统的LS成本函数相比,我们的方法可提高估计准确动力学参数的能力。这最终将导致更精确,可预测和可控制的生化模型。

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