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首页> 外文期刊>Cancer Informatics >CoGNaC: A Chaste Plugin for the Multiscale Simulation of Gene Regulatory Networks Driving the Spatial Dynamics of Tissues and Cancer
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CoGNaC: A Chaste Plugin for the Multiscale Simulation of Gene Regulatory Networks Driving the Spatial Dynamics of Tissues and Cancer

机译：CoGNaC：Chaste插件，用于基因调控网络的多尺度仿真，驱动组织和癌症的空间动态

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摘要

We introduce a Chaste plugin for the generation and the simulation of Gene Regulatory Networks (GRNs) in multiscale models of multicellular systems. Chaste is a widely used and versatile computational framework for the multiscale modeling and simulation of multicellular biological systems. The plugin, named CoGNaC (Chaste and Gene Networks for Cancer), allows the linking of the regulatory dynamics to key properties of the cell cycle and of the differentiation process in populations of cells, which can subsequently be modeled using different spatial modeling scenarios. The approach of CoGNaC focuses on the emergent dynamical behavior of gene networks, in terms of gene activation patterns characterizing the different cellular phenotypes of real cells and, especially, on the overall robustness to perturbations and biological noise. The integration of this approach within Chaste's modular simulation framework provides a powerful tool to model multicellular systems, possibly allowing for the formulation of novel hypotheses on gene regulation, cell differentiation, and, in particular, cancer emergence and development. In order to demonstrate the usefulness of CoGNaC over a range of modeling paradigms, two example applications are presented. The first of these concerns the characterization of the gene activation patterns of human T-helper cells. The second example is a multiscale simulation of a simplified intestinal crypt, in which, given certain conditions, tumor cells can emerge and colonize the tissue.
机译：我们介绍了一个Chaste插件，用于在多细胞系统的多尺度模型中生成和仿真基因调控网络（GRN）。 Chaste是用于多细胞生物系统的多尺度建模和仿真的一种广泛使用的通用计算框架。该插件名为CoGNaC（用于癌症的Chaste and Gene Networks），可将调节动力学与细胞周期和细胞群分化过程的关键特性链接起来，随后可使用不同的空间建模场景对其进行建模。 CoGNaC的方法侧重于基因网络出现的动态行为，涉及表征真实细胞不同细胞表型的基因激活模式，尤其是对扰动和生物学噪声的总体鲁棒性。该方法在Chaste的模块化仿真框架中的集成提供了一种强大的工具，可以对多细胞系统进行建模，从而可能提出有关基因调节，细胞分化，尤其是癌症发生和发展的新假设。为了证明CoGNaC在一系列建模范例中的有用性，提出了两个示例应用程序。其中第一个涉及人T辅助细胞基因激活模式的表征。第二个例子是简化的肠道隐窝的多尺度模拟，其中，在一定条件下，肿瘤细胞可以出现并在组织中定植。

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