Pairing experimentation and computational modeling to understand the role of tissue inducer cells in the development of lymphoid organs.
Pairing experimentation and computational modeling to understand the role of tissue inducer cells in the development of lymphoid organs.
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DOI：
10.3389/fimmu.2012.00172
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发表时间：
2012
影响因子：
7.3
通讯作者：
Coles MC
中科院分区：
文献类型：
--
作者：
Alden K;Timmis J;Andrews PS;Veiga-Fernandes H;Coles MC
遗传工具、成像技术和离体培养系统的使用为组织诱导细胞和相关信号通路在淋巴器官形成和功能中的作用提供了重要的见解。尽管实验技术取得了进步，但利用现有方法很难解剖复杂三维组织形成的分子和细胞过程。因此，已经开发了一套强大的模拟工具来模拟参与淋巴组织发育的过程。具体地说，不同的组织诱导剂细胞群体在动态形成佩耶尔斑块的作用已经被检查。利用系统工程的方法，开发了一个无偏的淋巴组织诱导细胞功能模型，该模型允许发展与体内观察到的统计学上没有差异的新行为。这些结果为利用统计方法探索模拟器如何预测不同生理条件下的细胞行为和结果提供了信心。这种被称为敏感性分析技术的方法，可以深入了解系统的组成部分（如特定的细胞类型、粘附分子或趋化因子）何时开始对观察到的行为产生影响，并量化组成部分对最终结果（淋巴组织的形成）的影响。通过在计算机模拟的设计、校准和分析中使用这种原则性方法，可以开发出一种强大的计算机工具，既可以进一步了解正在探索的生物系统，又可以作为生成假设的工具，这些假设可以利用实验方法进行测试。
The use of genetic tools, imaging technologies and ex vivo culture systems has provided significant insights into the role of tissue inducer cells and associated signaling pathways in the formation and function of lymphoid organs. Despite advances in experimental technologies, the molecular and cellular process orchestrating the formation of a complex three-dimensional tissue is difficult to dissect using current approaches. Therefore, a robust set of simulation tools have been developed to model the processes involved in lymphoid tissue development. Specifically, the role of different tissue inducer cell populations in the dynamic formation of Peyer’s patches has been examined. Utilizing approaches from systems engineering, an unbiased model of lymphoid tissue inducer cell function has been developed that permits the development of emerging behaviors that are statistically not different from that observed in vivo. These results provide the confidence to utilize statistical methods to explore how the simulator predicts cellular behavior and outcomes under different physiological conditions. Such methods, known as sensitivity analysis techniques, can provide insight into when a component part of the system (such as a particular cell type, adhesion molecule, or chemokine) begins to have an influence on observed behavior, and quantifies the effect a component part has on the end result: the formation of lymphoid tissue. Through use of such a principled approach in the design, calibration, and analysis of a computer simulation, a robust in silico tool can be developed which can both further the understanding of a biological system being explored, and act as a tool for the generation of hypotheses which can be tested utilizing experimental approaches.
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影响因子：
2
作者：
Jung C;Hugot JP;Barreau F
通讯作者：
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DOI：
10.1084/jem.20021294
发表时间：
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期刊：
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影响因子：
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通讯作者：
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作者：
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