Kazarnikov Alexey, Haario Heikki
Department of Mathematics and Physics, LUT University, Yliopistonkatu 34, 53850 Lappeenranta, Finland; Southern Mathematical Institute of the Vladikavkaz Scientific Centre of the Russian Academy of Sciences, 362027 Vladikavkaz, Russia.
Department of Mathematics and Physics, LUT University, Yliopistonkatu 34, 53850 Lappeenranta, Finland; Finnish Meteorological Institute, FI-00101, P.O. Box 503, Helsinki, Finland.
J Theor Biol. 2020 Sep 21;501:110319. doi: 10.1016/j.jtbi.2020.110319. Epub 2020 May 13.
Prevailing theories in biological pattern formation, such as in morphogenesis or multicellular structures development, have been based on purely chemical processes, with the Turing models as the prime example. Recent studies have challenged the approach, by underlining the role of mechanical forces. A quantitative discrimination of competing theories is difficult, however, due to the elusive character of the processes: different mechanisms may result in similar patterns, while patterns obtained with a fixed model and fixed parameter values, but with small random perturbations of initial values, will significantly differ in shape, while being of the "same" type. In this sense each model parameter value corresponds to a family of patterns, rather than a fixed solution. For this situation we create a likelihood that allows a statistically sound way to distinguish the model parameters that correspond to given patterns. The method allows us to identify model parameters of reaction-diffusion systems by using Turing patterns only, i.e., the steady-state solutions of the respective equations without the use of transient data or initial values. The method is tested with three classical models of pattern formation: the FitzHugh-Nagumo model, Gierer-Meinhardt system and Brusselator reaction-diffusion system. We quantify the accuracy achieved by different amounts of training data by Bayesian sampling methods. We demonstrate how a large enough ensemble of patterns leads to detection of very small but systematic structural changes, practically impossible to distinguish with the naked eye.
生物模式形成的主流理论,如形态发生或多细胞结构发育中的理论,一直基于纯粹的化学过程,其中图灵模型是主要例子。最近的研究对这种方法提出了挑战,强调了机械力的作用。然而,由于这些过程难以捉摸的特性,对相互竞争的理论进行定量区分很困难:不同的机制可能导致相似的模式,而使用固定模型和固定参数值,但初始值有小的随机扰动得到的模式,其形状会有显著差异,尽管属于“同一”类型。从这个意义上说,每个模型参数值对应于一族模式,而不是一个固定的解。针对这种情况,我们创建了一种似然性,它允许以一种统计上合理的方式来区分与给定模式对应的模型参数。该方法使我们能够仅通过使用图灵模式来识别反应扩散系统的模型参数,即相应方程的稳态解,而无需使用瞬态数据或初始值。该方法用三个经典的模式形成模型进行了测试:菲茨休 - 纳古莫模型、吉勒尔 - 迈因哈特系统和布鲁塞尔振子反应扩散系统。我们通过贝叶斯采样方法量化了不同数量的训练数据所达到的精度。我们展示了足够大的模式集合如何导致检测到非常小但系统的结构变化,而这些变化用肉眼几乎无法区分。