Institut Curie, Université PSL, 26 rue d'Ulm, 75005, Paris, France.
INSERM, U900, 26 rue d'Ulm, 75005, Paris, France.
Brief Bioinform. 2024 Sep 23;25(6). doi: 10.1093/bib/bbae509.
Multiscale models provide a unique tool for analyzing 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. These models 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 construct these models more easily, relying on PhysiCell Studio, the PhysiCell Graphical User Interface. A step-by-step tutorial is provided as Supplementary Material and all models are provided at https://physiboss.github.io/tutorial/.
多尺度模型为分析复杂过程提供了独特的工具，这些过程研究跨越空间和时间的不同尺度上发生的事件。在生物系统的背景下，这些模型可以模拟发生在细胞内水平的机制，如信号转导，以及细胞在细胞外水平上与其他细胞进行通信和协调的机制。这些模型旨在理解复杂疾病中观察到的遗传或环境失调的影响，描述病变组织与免疫系统之间的相互作用，并提出恢复病变表型的策略。构建这些多尺度模型仍然是一项非常复杂的任务，包括选择要考虑的组件、模拟过程的详细程度，或拟合参数以适应数据。另一个困难是需要专家知识来用 C++或 Python 等语言编写这些模型，这可能会阻碍非专家的参与。通过结构化描述形式化方法来简化这个过程——结合图形界面——对于使建模更容易被更广泛的科学界接受以及为高级用户简化这个过程至关重要。本文介绍了三个依赖于 PhysiBoSS 框架的多尺度模型示例，PhysiBoSS 是 PhysiCell 的一个附加组件，它将细胞内描述作为连续时间布尔模型包含到基于代理的方法中。本文展示了如何更轻松地使用 PhysiCell Studio，即 PhysiCell 图形用户界面来构建这些模型。逐步教程作为补充材料提供，所有模型都可在 https://physiboss.github.io/tutorial/ 上获得。
