Implementation of a regulatory gene network to simulate the TH1/2 differentiation in an agent-based model of hypersensitivity reactions
Implementation of a regulatory gene network to simulate the TH1/2 differentiation in an agent-based model of hypersensitivity reactions
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DOI：
10.1093/bioinformatics/btn135
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发表时间：
2008-06-01
期刊：
影响因子：
5.8
通讯作者：
Castiglione, Filippo
中科院分区：
文献类型：
--
作者：
Santoni, Daniele;Pedicini, Marco;Castiglione, Filippo
动机：在免疫应答中，T辅助细胞从前体类型TH0向TH1或TH2表型的不平衡分化通常导致病理状况。一般而言，偏向于TH1应答的免疫反应可能导致自身免疫疾病，而增强的TH2应答可能导致过敏反应。这项工作的目的是整合的TH分化的基因网络的超敏反应的代理为基础的模型。这样一个系统的实现引入了第二个层次的描述超越了介观层次的细胞间的互动的代理为基础的模型。细胞内水平包括基因激活和转录的细胞内部动态。基因调控网络包括已被发现参与TH细胞分化过程的基因相关分子。结果：模拟器再现了IgE介导的过敏反应的标志，并提供了一个例子，说明如何结合联合收割机的介观水平的描述免疫细胞的微观基因水平的动态。
Motivation: An unbalanced differentiation of T helper cells from precursor type TH0 to the TH1 or TH2 phenotype in immune responses often leads to a pathological condition. In general, immune reactions biased toward TH1 responses may result in auto-immune diseases, while enhanced TH2 responses may cause allergic reactions. The aim of this work is to integrate a gene network of the TH differentiation in an agent-based model of the hyper-sensitivity reaction. The implementation of such a system introduces a second level of description beyond the mesoscopic level of the inter-cellular interaction of the agent-based model. The intra-cellular level consists in the cell internal dynamics of gene activation and transcription. The gene regulatory network includes genes-related molecules that have been found to be involved in the differentiation process in TH cells.Results: The simulator reproduces the hallmarks of an IgE-mediated hypersensitive reaction and provides an example of how to combine the mesoscopic level description of immune cells with the microscopic gene-level dynamics.