Optimal experimental design in an epidermal growth factor receptor signalling and down-regulation model

Optimal experimental design in an epidermal growth factor receptor signalling and down-regulation model
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DOI:
10.1049/iet-syb:20060065
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发表时间:
2007-05-01
影响因子:
2.3
通讯作者:
Sethna, J. P.
Sethna, J. P.
中科院分区:
生物学4区
文献类型:
--
作者:
Casey, F. P.;Baird, D.;Sethna, J. P.

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我们应用最优实验设计的方法,表皮生长因子受体信号转导,贩运和下调的微分方程模型。该模型结合了最近发现的蛋白质复合物的作用,该蛋白质复合物由E3泛素连接酶、Cbl、鸟嘌呤交换因子(GEF)、Cool-1(β-Pix)和Rho家族G蛋白Cdc 42组成。该复合物已被认为在破坏受体下调中是重要的。我们证明,模型的相互作用可以准确地再现实验观察,它们可以用来预测伴随的不确定性,我们可以应用最佳实验设计的想法,建议新的实验,减少系统的不可测组件的不确定性。
We apply the methods of optimal experimental design to a differential equation model for epidermal growth factor receptor signalling, trafficking and down-regulation. The model incorporates the role of a recently discovered protein complex made up of the E3 ubiquitin ligase, Cbl, the guanine exchange factor (GEF), Cool-1 (beta-Pix) and the Rho family G protein Cdc42. The complex has been suggested to be important in disrupting receptor down-regulation. We demonstrate that the model interactions can accurately reproduce the experimental observations, that they can be used to make predictions with accompanying uncertainties, and that we can apply ideas of optimal experimental design to suggest new experiments that reduce the uncertainty on unmeasurable components of the system.