论文标题

确切的基于晶格的随机细胞培养仿真算法,结合了自发和接触依赖性反应

Exact lattice-based stochastic cell culture simulation algorithms incorporating spontaneous and contact-dependent reactions

论文作者

Boldog, Peter

论文摘要

在本文中,我们解决了细胞运动和分裂的建模问题,特别关注了基于晶格的,精确的随机模拟框架中的体积排除现象。我们提出了一种新的精确方法,称为降低速率方法-RRM,它比以前使用的大量细胞要快得多。此外,我们引入了三种新型反应类型:接触抑制,接触促进和自发反应。据我们所知,这些反应类型尚未在基于晶格的细胞培养物随机模拟中考虑到。这些新类型的事件可以很容易地应用于复杂的系统,从而能够生成生物可行的随机细胞培养模拟。此外,我们表明排除算法和我们的RRM算法在数学上是等效的,因为即使在新引入的反应类型中,也属于两种方法中的下一个反应和相应的索期时间都属于相同的反应和时间分布。 精确的,基于代理的细胞培养模拟方法似乎被低估了,并且主要用作验证相应随机模型的确定性近似值的基准测试工具。我们提出的方法是精确的,它们易于实现,具有较高的预测价值,并且可以通过新功能方便地扩展。因此,这些方法具有巨大的潜力。

In this paper, we address the modeling issues of cell movement and division with a special focus on the phenomenon of volume exclusion in a lattice-based, exact stochastic simulation framework. We propose a new exact method, called Reduced Rate Method -- RRM, that is substantially quicker than the previously used exclusion method, for large number of cells. In addition, we introduce three novel reaction types: the contact-inhibited, the contact-promoted, and the spontaneous reactions. To the best of our knowledge, these reaction types have not been taken into account in lattice-based stochastic simulations of cell cultures. These new types of events may be easily applied to complicated systems, enabling the generation of biologically feasible stochastic cell culture simulations. Furthermore, we show that the exclusion algorithm and our RRM algorithm are mathematically equivalent in the sense that the next reaction to be realized and the corresponding sojourn time both belong to the same reaction and time distributions in the two approaches -- even with the newly introduced reaction types. Exact, agent-based, stochastic methods of cell culture simulations seem to be undervalued and are mostly used as benchmarking tools to validate deterministic approximations of the corresponding stochastic models. Our proposed methods are exact, they are easy to implement, have a high predictive value, and can be conveniently extended with new features. Therefore, these approaches promise a great potential.

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