In silico investigation of novel biological pathways: The role of CD200 in regulation of T cell priming in experimental autoimmune encephalomyelitis
In silico investigation of novel biological pathways: The role of CD200 in regulation of T cell priming in experimental autoimmune encephalomyelitis
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DOI：
10.1016/j.biosystems.2013.03.007
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发表时间：
2013-05-01
期刊：
影响因子：
1.6
通讯作者：
Kumar, Vipin
中科院分区：
文献类型：
--
作者：
Greaves, Richard B.;Read, Mark;Kumar, Vipin
使用模拟来研究生物领域将不可避免地导致需要扩展现有的模拟，因为这些领域的新领域变得更加充分地了解。这样的模拟扩展可能需要加入更多的细胞类型、分子或分子途径，所有这些都可以对模拟行为产生深远的影响。在生物领域没有很好描述的情况下，必须采用结构化的开发方法，以确保扩展的模拟与其前身很好地结合。我们依靠迭代模拟开发和灵敏度分析来开发和讨论这样的方法论。通过对实验性自身免疫性脑脊髓炎(EAE)的案例研究模拟，证明了该方法的有效性。EAE是一种多发性硬化症的小鼠T细胞介导的自身免疫性疾病模型，在该模型中，它被用来研究另一条调节通路的活性。我们讨论了在研究特征不佳的生物机制时，这种方法的应用如何防止创建不适当的生物学模拟表示。(C)2013爱思唯尔爱尔兰有限公司。保留所有权利。
The use of simulation to investigate biological domains will inevitably lead to the need to extend existing simulations as new areas of these domains become more fully understood. Such simulation extensions can entail the incorporation of additional cell types, molecules or molecular pathways, all of which can exert a profound influence on the simulation behaviour. Where the biological domain is not well characterised, a structured development methodology must be employed to ensure that the extended simulation is well aligned with its predecessor. We develop and discuss such a methodology, relying on iterative simulation development and sensitivity analysis. The utility of this methodology is demonstrated using a case study simulation of experimental autoimmune encephalomyelitis (EAE), a murine T cell-mediated autoimmune disease model of multiple sclerosis, where it is used to investigate the activity of an additional regulatory pathway. We discuss how application of this methodology guards against creating inappropriate simulation representations of the biology when investigating poorly characterised biological mechanisms. (C) 2013 Elsevier Ireland Ltd. All rights reserved.