Computational Biology & Health Informatics, Department of Computer Science, University of Oxford, Oxford, UK.
Pharma Research and Early Development, Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
WIREs Mech Dis. 2023 Jan;15(1):e1581. doi: 10.1002/wsbm.1581. Epub 2022 Aug 26.
The L-type calcium current ( ) plays a critical role in cardiac electrophysiology, and models of are vital tools to predict arrhythmogenicity of drugs and mutations. Five decades of measuring and modeling have resulted in several competing theories (encoded in mathematical equations). However, the introduction of new models has not typically been accompanied by a data-driven critical comparison with previous work, so that it is unclear which model is best suited for any particular application. In this review, we describe and compare 73 published mammalian models and use simulated experiments to show that there is a large variability in their predictions, which is not substantially diminished when grouping by species or other categories. We provide model code for 60 models, list major data sources, and discuss experimental and modeling work that will be required to reduce this huge list of competing theories and ultimately develop a community consensus model of . This article is categorized under: Cardiovascular Diseases > Computational Models Cardiovascular Diseases > Molecular and Cellular Physiology.
L 型钙电流 ( ) 在心脏电生理学中起着关键作用,而 模型是预测药物和突变致心律失常性的重要工具。五十年来,对 的测量和建模产生了几种相互竞争的理论(用数学方程式表示)。然而,新模型的引入通常没有伴随与以前工作的数据驱动的关键比较,因此不清楚哪种模型最适合任何特定的应用。在这篇综述中,我们描述和比较了 73 个已发表的哺乳动物 模型,并使用模拟实验表明,它们的预测存在很大的可变性,而按物种或其他类别分组并不能显著降低这种可变性。我们为 60 个模型提供了模型代码,列出了主要的数据来源,并讨论了减少这一庞大的竞争理论清单并最终开发出 模型的社区共识模型所需的实验和建模工作。本文属于以下类别:心血管疾病 > 计算模型心血管疾病 > 分子和细胞生理学。