Figueredo Grazziela P, Siebers Peer-Olaf, Owen Markus R, Reps Jenna, Aickelin Uwe
School of Computer Science, The University of Nottingham, Nottingham, United Kingdom.
Centre for Mathematical Medicine and Biology, School of Mathematical Sciences, The University of Nottingham, Nottingham, United Kingdom.
PLoS One. 2014 Apr 21;9(4):e95150. doi: 10.1371/journal.pone.0095150. eCollection 2014.
There is great potential to be explored regarding the use of agent-based modelling and simulation as an alternative paradigm to investigate early-stage cancer interactions with the immune system. It does not suffer from some limitations of ordinary differential equation models, such as the lack of stochasticity, representation of individual behaviours rather than aggregates and individual memory. In this paper we investigate the potential contribution of agent-based modelling and simulation when contrasted with stochastic versions of ODE models using early-stage cancer examples. We seek answers to the following questions: (1) Does this new stochastic formulation produce similar results to the agent-based version? (2) Can these methods be used interchangeably? (3) Do agent-based models outcomes reveal any benefit when compared to the Gillespie results? To answer these research questions we investigate three well-established mathematical models describing interactions between tumour cells and immune elements. These case studies were re-conceptualised under an agent-based perspective and also converted to the Gillespie algorithm formulation. Our interest in this work, therefore, is to establish a methodological discussion regarding the usability of different simulation approaches, rather than provide further biological insights into the investigated case studies. Our results show that it is possible to obtain equivalent models that implement the same mechanisms; however, the incapacity of the Gillespie algorithm to retain individual memory of past events affects the similarity of some results. Furthermore, the emergent behaviour of ABMS produces extra patters of behaviour in the system, which was not obtained by the Gillespie algorithm.
将基于主体的建模与仿真作为一种替代范式来研究早期癌症与免疫系统的相互作用,具有巨大的探索潜力。它不存在常微分方程模型的一些局限性,比如缺乏随机性、无法表示个体行为而非总体行为以及个体记忆。在本文中,我们以早期癌症为例,研究基于主体的建模与仿真在与常微分方程模型的随机版本对比时的潜在贡献。我们寻求以下问题的答案:(1)这种新的随机公式是否能产生与基于主体版本相似的结果?(2)这些方法能否互换使用?(3)与吉莱斯皮结果相比,基于主体的模型结果是否显示出任何优势?为了回答这些研究问题,我们研究了三个描述肿瘤细胞与免疫元素相互作用的成熟数学模型。这些案例研究在基于主体的视角下进行了重新概念化,并也转换为了吉莱斯皮算法公式。因此,我们在这项工作中的兴趣在于就不同仿真方法的可用性展开方法学讨论,而非对所研究的案例提供进一步的生物学见解。我们的结果表明,可以获得实现相同机制的等效模型;然而,吉莱斯皮算法无法保留过去事件的个体记忆影响了一些结果的相似性。此外,基于主体的建模与仿真的涌现行为在系统中产生了额外的行为模式,这是吉莱斯皮算法所无法获得的。