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/.
翻译:多尺度模型为研究跨时空不同尺度发生的复杂过程提供了独特工具。在生物系统背景下,此类模型能够模拟细胞内水平(如信号传导)和细胞外水平(细胞间通信与协调)的机制。其目标在于理解复杂疾病中观察到的遗传或环境失调的影响,描述病理组织与免疫系统间的相互作用,并提出逆转疾病表型的策略。构建这些多尺度模型仍是极其复杂的任务,包括需考虑组件的选择、模拟过程的细节层次以及参数与数据的拟合。另一重困难在于需要使用C++或Python等语言编程这些模型所需的专业知识,这可能阻碍非专业人士的参与。通过结构化描述形式(结合图形界面)简化此过程,对于让更广泛的科学界能够进行建模以及为高级用户优化流程至关重要。本文介绍了三个依赖PhysiBoSS框架的多尺度模型案例,该框架作为PhysiCell的扩展模块,将细胞内描述以连续时间布尔模型形式整合到基于智能体的建模方法中。文章展示了如何借助PhysiCell图形用户界面PhysiCell Studio轻松构建此类模型。逐步教程作为补充材料提供,所有模型可通过以下网址获取:https://physiboss.github.io/tutorial/。