Chemical and Biological Engineering, Northwestern University, Evanston, Illinois, United States of America.
Biology, University of Washington, Seattle, Washington, United States of America.
PLoS Comput Biol. 2024 Mar 8;20(3):e1011917. doi: 10.1371/journal.pcbi.1011917. eCollection 2024 Mar.
Computational models enable scientists to understand observed dynamics, uncover rules underlying behaviors, predict experimental outcomes, and generate new hypotheses. There are countless modeling approaches that can be used to characterize biological systems, further multiplied when accounting for the variety of model design choices. Many studies focus on the impact of model parameters on model output and performance; fewer studies investigate the impact of model design choices on biological insight. Here we demonstrate why model design choices should be deliberate and intentional in context of the specific research system and question. In this study, we analyze agnostic and broadly applicable modeling choices at three levels-system, cell, and environment-within the same agent-based modeling framework to interrogate their impact on temporal, spatial, and single-cell emergent dynamics. We identify key considerations when making these modeling choices, including the (i) differences between qualitative vs. quantitative results driven by choices in system representation, (ii) impact of cell-to-cell variability choices on cell-level and temporal trends, and (iii) relationship between emergent outcomes and choices of nutrient dynamics in the environment. This generalizable investigation can help guide the choices made when developing biological models that aim to characterize spatial-temporal dynamics.
计算模型使科学家能够理解观察到的动态，揭示行为背后的规则，预测实验结果，并生成新的假设。有无数种可以用来描述生物系统的建模方法，如果考虑到模型设计选择的多样性，那么这个数字还会进一步增加。许多研究都集中在模型参数对模型输出和性能的影响上；而较少的研究则探讨模型设计选择对生物学见解的影响。在这里，我们将展示为什么在特定的研究系统和问题背景下，模型设计选择应该是深思熟虑和有目的的。在这项研究中，我们在同一个基于 agent 的建模框架内，分析了系统、细胞和环境三个层次上的无偏和广泛适用的建模选择，以探究它们对时间、空间和单细胞涌现动态的影响。我们确定了在做出这些建模选择时需要考虑的关键因素，包括：（i）系统表示选择导致的定性与定量结果之间的差异；（ii）细胞间变异性选择对细胞水平和时间趋势的影响；（iii）涌现结果与环境中营养动态选择之间的关系。这种可推广的研究可以帮助指导开发旨在描述时空动态的生物学模型时做出的选择。
