BACKGROUND Reproducing cell processes using an in silico system is an essential tool for understanding the underlying mechanisms and emergent properties of this extraordinary complex biological machine. However, computational models are seldom applied in the field of intracellular trafficking. In a cell, numerous molecular interactions occur on the surface or in the interior of membrane-bound compartments that continually change position and undergo dynamic processes of fusion and fission. At present, the available simulation tools are not suitable to develop models that incorporate the dynamic evolution of the cell organelles. RESULTS We developed a modeling platform combining Repast (Agent-Based Modeling, ABM) and COPASI (Differential Equations, ODE) that can be used to reproduce complex networks of molecular interactions. These interactions occur in dynamic cell organelles that change position and composition over the course of time. These two modeling strategies are fundamentally different and comprise of complementary capabilities. The ODEs can easily model the networks of molecular interactions, signaling cascades, and complex metabolic reactions. On the other hand, ABM software is especially suited to simulate the movement, interaction, fusion, and fission of dynamic organelles. We used the combined ABM-ODE platform to simulate the transport of soluble and membrane-associated cargoes that move along an endocytic route composed of early, sorting, recycling and late endosomes. We showed that complex processes that strongly depend on transport can be modeled. As an example, the hydrolysis of a GM2-like glycolipid was programmed by adding a trans-Golgi network compartment, lysosomal enzyme trafficking, endosomal acidification, and cholesterol processing to the simulation model. CONCLUSIONS The model captures the highly dynamic nature of cell compartments that fuse and divide, creating different conditions for each organelle. We expect that this modeling strategy will be useful to understand the logic underlying the organization and function of the endomembrane system. REVIEWERS This article was reviewed by Drs. Rafael Fernández-Chacón, James Faeder, and Thomas Simmen.

中文翻译：

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通过结合ODE和基于代理的建模策略来重建内体的组织和功能。

背景技术使用计算机系统（in silico system）来繁殖细胞过程是理解这种异常复杂的生物机器的潜在机制和新兴特性的重要工具。但是，计算模型很少用于细胞内运输领域。在一个细胞中，与膜结合的隔室的表面或内部会发生许多分子相互作用，这些相互作用会不断改变位置并经历融合和裂变的动态过程。目前，可用的仿真工具不适合开发包含细胞器动态演变的模型。结果我们开发了一个结合了Repast（基于代理的建模，ABM）和COPASI（微分方程，ODE）的建模平台，可用于复制复杂的分子相互作用网络。这些相互作用发生在动态细胞器中，该细胞器随时间改变位置和组成。这两种建模策略根本不同，并且包含互补功能。ODE可以轻松模拟分子相互作用，信号级联和复杂代谢反应的网络。另一方面，ABM软件特别适合于模拟动态细胞器的运动，相互作用，融合和裂变。我们使用组合的ABM-ODE平台来模拟可溶和膜相关货物的运输，这些货物沿着由早期，分选，回收和晚期内体组成的内吞途径移动。我们表明，可以对高度依赖运输的复杂过程进行建模。举个例子，通过在模拟模型中添加反式高尔基体网络隔室，溶酶体酶运输，内体酸化和胆固醇加工来编程GM2样糖脂的水解过程。结论该模型捕获了融合和分裂的细胞室的高度动态特性，为每个细胞器创造了不同的条件。我们希望这种建模策略将有助于理解内膜系统的组织和功能的逻辑。评论者本文由Drs。Dr.撰写。拉斐尔·费尔南德斯·查孔，詹姆斯·费德和托马斯·西门。为每个细胞器创造不同的条件。我们希望这种建模策略将有助于理解内膜系统的组织和功能的逻辑。评论者本文由Drs。Dr.撰写。拉斐尔·费尔南德斯·查孔，詹姆斯·费德和托马斯·西门。为每个细胞器创造不同的条件。我们希望这种建模策略将有助于理解内膜系统的组织和功能的逻辑。评论者本文由Drs。Dr.撰写。拉斐尔·费尔南德斯·查孔，詹姆斯·费德和托马斯·西门。