School of Mathematical Sciences, Queensland University of Technology (QUT), Brisbane, Australia.
Institute of Health and Biomedical Innovation, QUT, Kelvin Grove, Australia.
Bull Math Biol. 2019 Mar;81(3):676-698. doi: 10.1007/s11538-018-0532-1. Epub 2018 Nov 15.
We present a novel framework to parameterise a mathematical model of cell invasion that describes how a population of melanoma cells invades into human skin tissue. Using simple experimental data extracted from complex experimental images, we estimate three model parameters: (i) the melanoma cell proliferation rate, [Formula: see text]; (ii) the melanoma cell diffusivity, D; and (iii) [Formula: see text], a constant that determines the rate that melanoma cells degrade the skin tissue. The Bayesian sequential learning framework involves a sequence of increasingly sophisticated experimental data from: (i) a spatially uniform cell proliferation assay; (ii) a two-dimensional circular barrier assay; and (iii) a three-dimensional invasion assay. The Bayesian sequential learning approach leads to well-defined parameter estimates. In contrast, taking a naive approach that attempts to estimate all parameters from a single set of images from the same experiment fails to produce meaningful results. Overall, our approach to inference is simple-to-implement, computationally efficient, and well suited for many cell biology phenomena that can be described by low-dimensional continuum models using ordinary differential equations and partial differential equations. We anticipate that this Bayesian sequential learning framework will be relevant in other biological contexts where it is challenging to extract detailed, quantitative biological measurements from experimental images and so we must rely on using relatively simple measurements from complex images.
我们提出了一种新的框架,用于参数化描述黑色素瘤细胞如何侵入人体皮肤组织的细胞入侵数学模型。使用从复杂实验图像中提取的简单实验数据,我们估计了三个模型参数:(i)黑色素瘤细胞的增殖率 [Formula: see text];(ii)黑色素瘤细胞的扩散系数 D;以及(iii)[Formula: see text],这是一个决定黑色素瘤细胞降解皮肤组织速度的常数。贝叶斯序贯学习框架涉及从以下三种越来越复杂的实验数据的序列:(i)空间均匀的细胞增殖测定;(ii)二维圆形障碍测定;和(iii)三维入侵测定。贝叶斯序贯学习方法导致了明确定义的参数估计。相比之下,采取一种从同一实验的同一组图像中尝试估计所有参数的简单方法无法产生有意义的结果。总体而言,我们的推理方法易于实现、计算效率高,非常适合许多可以用常微分方程和偏微分方程描述的低维连续模型来描述的细胞生物学现象。我们预计,这种贝叶斯序贯学习框架将在其他生物学背景下具有相关性,在这些背景下,从实验图像中提取详细、定量的生物学测量值具有挑战性,因此我们必须依赖于从复杂图像中使用相对简单的测量值。