Colyer Blair, Bak Maciej, Basanta David, Noble Robert
Department of Mathematics City, University of London London UK.
Department of Integrated Mathematical Oncology H. Lee Moffitt Cancer Center and Research Institute Tampa Florida USA.
Evol Appl. 2024 May 2;17(5):e13687. doi: 10.1111/eva.13687. eCollection 2024 May.
Spatial agent-based models are frequently used to investigate the evolution of solid tumours subject to localized cell-cell interactions and microenvironmental heterogeneity. As spatial genomic, transcriptomic and proteomic technologies gain traction, spatial computational models are predicted to become ever more necessary for making sense of complex clinical and experimental data sets, for predicting clinical outcomes, and for optimizing treatment strategies. Here we present a non-technical step by step guide to developing such a model from first principles. Stressing the importance of tailoring the model structure to that of the biological system, we describe methods of increasing complexity, from the basic Eden growth model up to off-lattice simulations with diffusible factors. We examine choices that unavoidably arise in model design, such as implementation, parameterization, visualization and reproducibility. Each topic is illustrated with examples drawn from recent research studies and state of the art modelling platforms. We emphasize the benefits of simpler models that aim to match the complexity of the phenomena of interest, rather than that of the entire biological system. Our guide is aimed at both aspiring modellers and other biologists and oncologists who wish to understand the assumptions and limitations of the models on which major cancer studies now so often depend.
基于主体的空间模型经常用于研究受局部细胞-细胞相互作用和微环境异质性影响的实体瘤的演变。随着空间基因组学、转录组学和蛋白质组学技术的兴起,空间计算模型预计对于理解复杂的临床和实验数据集、预测临床结果以及优化治疗策略将变得越来越必要。在此,我们提供一份从基本原理出发逐步开发此类模型的非技术性指南。我们强调使模型结构与生物系统结构相匹配的重要性,描述了从基本的伊登生长模型到具有扩散因子的非格点模拟等增加模型复杂性的方法。我们审视了模型设计中不可避免会出现的选择,例如实现方式、参数化、可视化和可重复性。每个主题都通过近期研究和前沿建模平台中的实例进行说明。我们强调旨在匹配感兴趣现象的复杂性而非整个生物系统复杂性的更简单模型的益处。我们的指南既面向有抱负的建模者,也面向其他希望了解当前许多重大癌症研究所依赖模型的假设和局限性的生物学家及肿瘤学家。