论文标题

建模人心房细胞时,降低复杂性和无法识别性

Reducing complexity and unidentifiability when modelling human atrial cells

论文作者

Houston, C., Marchand, B., Engelbert, L., Cantwell, C. D.

论文摘要

心脏建模中细胞动作电位的数学模型已经变得越来越复杂,尤其是在控制单个离子通道电流开放和关闭的门控动力学中。随着心脏模型促进个性化医学的使用以告知临床决策,因此了解从校准到实验数据中隐藏的参数估计中隐藏的不确定性至关重要。这项研究将近似贝叶斯计算应用于其原始数据集中,将四个离子通道的门控动力学重新校准,从而在给定可用的实验数据的情况下选择单个独特值的不确定性和指示潜在问题的不确定性和指示。研究了两种方法以减少存在的不确定性:将模型重新校准到更完整的数据集中,并使用较少的参数来限制的不太复杂的公式。重新校准的模型被插入完整的细胞模型中,以研究对动作电位的整体影响。更完整的数据集的使用不会消除参数估计中存在的不确定性。不太复杂的模型,特别是对于快速钠电流,与较低的参数不确定性和提高的计算速度相适应了实验数据。

Mathematical models of a cellular action potential in cardiac modelling have become increasingly complex, particularly in gating kinetics which control the opening and closing of individual ion channel currents. As cardiac models advance towards use in personalised medicine to inform clinical decision-making, it is critical to understand the uncertainty hidden in parameter estimates from their calibration to experimental data. This study applies approximate Bayesian computation to re-calibrate the gating kinetics of four ion channels in two existing human atrial cell models to their original datasets, providing a measure of uncertainty and indication of potential issues with selecting a single unique value given the available experimental data. Two approaches are investigated to reduce the uncertainty present: re-calibrating the models to a more complete dataset and using a less complex formulation with fewer parameters to constrain. The re-calibrated models are inserted back into the full cell model to study the overall effect on the action potential. The use of more complete datasets does not eliminate uncertainty present in parameter estimates. The less complex model, particularly for the fast sodium current, gave a better fit to experimental data alongside lower parameter uncertainty and improved computational speed.

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