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基于近似贝叶斯计算的单相和双相肿瘤生长的基于代理的模型校准。

Calibration of agent based models for monophasic and biphasic tumour growth using approximate Bayesian computation.

机构信息

School of Mathematical Sciences, Queensland University of Technology, Brisbane, QLD, Australia.

Centre for Data Science, Queensland University of Technology, Brisbane, QLD, Australia.

出版信息

J Math Biol. 2024 Feb 15;88(3):28. doi: 10.1007/s00285-024-02045-4.

Abstract

Agent-based models (ABMs) are readily used to capture the stochasticity in tumour evolution; however, these models are often challenging to validate with experimental measurements due to model complexity. The Voronoi cell-based model (VCBM) is an off-lattice agent-based model that captures individual cell shapes using a Voronoi tessellation and mimics the evolution of cancer cell proliferation and movement. Evidence suggests tumours can exhibit biphasic growth in vivo. To account for this phenomena, we extend the VCBM to capture the existence of two distinct growth phases. Prior work primarily focused on point estimation for the parameters without consideration of estimating uncertainty. In this paper, approximate Bayesian computation is employed to calibrate the model to in vivo measurements of breast, ovarian and pancreatic cancer. Our approach involves estimating the distribution of parameters that govern cancer cell proliferation and recovering outputs that match the experimental data. Our results show that the VCBM, and its biphasic extension, provides insight into tumour growth and quantifies uncertainty in the switching time between the two phases of the biphasic growth model. We find this approach enables precise estimates for the time taken for a daughter cell to become a mature cell. This allows us to propose future refinements to the model to improve accuracy, whilst also making conclusions about the differences in cancer cell characteristics.

摘要

基于代理的模型 (ABM) 常用于捕获肿瘤进化中的随机性;然而,由于模型的复杂性,这些模型通常难以通过实验测量进行验证。基于 Voronoi 细胞的模型 (VCBM) 是一种非格点基于代理的模型,它使用 Voronoi 镶嵌来捕获单个细胞的形状,并模拟癌细胞增殖和运动的演化。有证据表明,肿瘤在体内可以表现出双相生长。为了说明这一现象,我们将 VCBM 扩展到了可以捕捉两种不同生长阶段的存在。之前的工作主要集中在参数的点估计上,而没有考虑到估计不确定性。在本文中,我们使用近似贝叶斯计算来对模型进行校准,以匹配乳腺癌、卵巢癌和胰腺癌的体内测量数据。我们的方法涉及估计控制癌细胞增殖的参数的分布,并恢复与实验数据匹配的输出。我们的结果表明,VCBM 及其双相扩展为肿瘤生长提供了深入的了解,并量化了双相生长模型中两个阶段之间切换时间的不确定性。我们发现这种方法可以精确估计一个子细胞成为成熟细胞所需的时间。这使我们能够提出对模型进行未来改进的建议,以提高准确性,同时也对癌细胞特性的差异做出结论。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c890/10869399/38fd75bc5fb0/285_2024_2045_Fig1_HTML.jpg

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