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Abstract：
Multiscale models provide a unique tool for studying complex processes that study events occurring at different scales across space and time. In the context of biological systems, such models can simulate mechanisms happening at the intracellular level such as signaling, and at the extracellular level where cells communicate and coordinate with other cells. They aim to understand the impact of genetic or environmental deregulation observed in complex diseases, describe the interplay between a pathological tissue and the immune system, and suggest strategies to revert the diseased phenotypes. The construction of these multiscale models remains a very complex task, including the choice of the components to consider, the level of details of the processes to simulate, or the fitting of the parameters to the data. One additional difficulty is the expert knowledge needed to program these models in languages such as C++ or Python, which may discourage the participation of non-experts. Simplifying this process through structured description formalisms - coupled with a graphical interface - is crucial in making modeling more accessible to the broader scientific community, as well as streamlining the process for advanced users. This article introduces three examples of multiscale models which rely on the framework PhysiBoSS, an add-on of PhysiCell that includes intracellular descriptions as continuous time Boolean models to the agent-based approach. The article demonstrates how to easily construct such models, relying on PhysiCell Studio, the PhysiCell Graphical User Interface. A step-by-step tutorial is provided as a Supplementary Material and all models are provided at: https://physiboss.github.io/tutorial/.
摘要：
多尺度模型为研究复杂过程提供了独特的工具，这些过程研究跨空间和时间在不同尺度上发生的事件。在生物系统的背景下，这样的模型可以模拟发生在细胞内水平的机制，如信号，在细胞外水平，细胞与其他细胞交流和协调。他们旨在了解在复杂疾病中观察到的遗传或环境放松管制的影响，描述病理组织和免疫系统之间的相互作用，并提出恢复患病表型的策略。这些多尺度模型的构建仍然是一项非常复杂的任务，包括要考虑的组件的选择，要模拟的过程的细节水平，或参数对数据的拟合。另一个困难是用C++或Python等语言编程这些模型所需的专业知识。这可能会阻碍非专家的参与。通过结构化的描述形式简化这个过程-加上图形界面-对于使建模更容易被更广泛的科学界访问至关重要。以及简化高级用户的流程。本文介绍了三个依赖于PhysiBoSS框架的多尺度模型示例，PhysiCell的附加组件，其中包括作为基于代理的方法的连续时间布尔模型的细胞内描述。本文演示了如何轻松构建此类模型，依靠PhysiCell工作室，PhysiCell图形用户界面。分步教程作为补充材料提供，所有模型都在以下位置提供：https://physiboss。github.io/tutorial/.
