Utilising a simulation platform to understand the effect of domain model assumptions.
Utilising a simulation platform to understand the effect of domain model assumptions.
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DOI：
10.1007/s11047-014-9428-7
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发表时间：
2015
影响因子：
2.1
通讯作者：
Coles M
中科院分区：
文献类型：
--
作者：
Alden K;Andrews PS;Veiga-Fernandes H;Timmis J;Coles M
计算和数学建模方法越来越多地被采用，试图进一步我们对复杂生物系统的理解。这种方法可能会受到强烈的批评，因为所捕获的生物系统的实质性方面目前尚不清楚，这意味着需要做出可能对模拟响应产生关键影响的假设。我们利用CoSMoS过程开发了一种基于药物的模拟Peyer’s patches （PP）形成的方法，PP是肠道相关的淋巴器官，在启动对感染的适应性免疫反应中起关键作用。尽管遗传工具、成像技术和离体培养系统的使用已经为PP发育过程中涉及的细胞成分和相关途径提供了重要的见解，但使用这些方法无法解决的有趣问题仍然存在，并且已经将这些合理的假设引入到我们的模型中以解决这一问题。在这里，我们不关注模型本身的发展，而是演示如何使用生成的模拟来评估这些假设如何影响模拟响应。例如，我们考虑了我们假设的影响，即淋巴组织细胞向肠道的迁移速度在PP发育过程中保持不变。我们证明，对领域模型构建过程中所做的假设进行分析，既可以增加对模型作为其捕获的生物系统的表示的信心，也可以建议需要进一步进行生物实验的领域。
Computational and mathematical modelling approaches are increasingly being adopted in attempts to further our understanding of complex biological systems. This approach can be subjected to strong criticism as substantial aspects of the biological system being captured are not currently known, meaning assumptions need to be made that could have a critical impact on simulation response. We have utilised the CoSMoS process in the development of an agent-based simulation of the formation of Peyer’s patches (PP), gut-associated lymphoid organs that have a key role in the initiation of adaptive immune responses to infection. Although the use of genetic tools, imaging technologies and ex vivo culture systems has provided significant insight into the cellular components and associated pathways involved in PP development, interesting questions remain that cannot be addressed using these approaches, and as such well justified assumptions have been introduced into our model to counter this. Here we focus not on the development of the model itself, but instead demonstrate how the resultant simulation can be used to assess how these assumptions impact the simulation response. For example, we consider the impact of our assumption that the migration rate of lymphoid tissue cells into the gut remains constant throughout PP development. We demonstrate that an analysis of the assumptions made in the construction of the domain model may either increase confidence in the model as a representation of the biological system it captures, or may suggest areas where further biological experimentation is required.
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DOI：
10.1084/jem.20021294
发表时间：
2003-05-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Luther SA;Ansel KM;Cyster JG
通讯作者：
Cyster JG
影响因子：
7.3
作者：
Patel, Amisha;Harker, Nicola;Veiga-Fernandes, Henrique
通讯作者：
Veiga-Fernandes, Henrique
DOI：
10.3102/10769986025002101
发表时间：
2000-06-01
影响因子：
2.4
作者：
Vargha, A;Delaney, HD
通讯作者：
Delaney, HD
影响因子：
4.4
作者：
Yoshida, H;Kawamoto, H;Nishikawa, S
通讯作者：
Nishikawa, S
影响因子：
4.4
作者：
Mebius, RE;Miyamoto, T;Akashi, K
通讯作者：
Akashi, K