Computational modeling of cellular signaling processes embedded into dynamic spatial contexts
Computational modeling of cellular signaling processes embedded into dynamic spatial contexts
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DOI：
10.1038/nmeth.1861
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发表时间：
2012-03-01
期刊：
影响因子：
48
通讯作者：
Meier-Schellersheim, Martin
中科院分区：
文献类型：
--
作者：
Angermann, Bastian R.;Klauschen, Frederick;Meier-Schellersheim, Martin
细胞信号传递过程依赖于分子组成的时空分布。多色、高分辨率显微镜可以对这种分布进行详细的评估，为探索多分子复合体动态组装的机制及其在塑造细胞行为中的作用的细粒度计算模型提供输入。然而，将复杂的分子反应级联和动态细胞形态中信号成分的空间定位都纳入到这样的模型中是具有挑战性的。在这里，我们介绍了一种方法来解决这些挑战，通过自动生成复杂反应网络的计算表示，基于嵌入到详细的、自适应的细胞形态模型中的简单双分子相互作用规则。以酵母中受体介导的细胞黏附和信号诱导的局部丝裂原活化蛋白激酶(MAPK)激活为例，我们说明了这种模拟技术为细胞生物学过程提供洞察力的能力。通过直观的图形界面和编程库，可以访问在新版本的免疫工具集中实现的建模算法。
Cellular signaling processes depend on spatiotemporal distributions of molecular components. Multicolor, high-resolution microscopy permits detailed assessment of such distributions, providing input for fine-grained computational models that explore mechanisms governing dynamic assembly of multimolecular complexes and their role in shaping cellular behavior. However, it is challenging to incorporate into such models both complex molecular reaction cascades and the spatial localization of signaling components in dynamic cellular morphologies. Here we introduce an approach to address these challenges by automatically generating computational representations of complex reaction networks based on simple bimolecular interaction rules embedded into detailed, adaptive models of cellular morphology. Using examples of receptor-mediated cellular adhesion and signal-induced localized mitogen-activated protein kinase (MAPK) activation in yeast, we illustrate the capacity of this simulation technique to provide insights into cell biological processes. The modeling algorithms, implemented in a new version of the Simmune toolset, are accessible through intuitive graphical interfaces and programming libraries.