Quantitative analysis of ultrasensitive responses
Quantitative analysis of ultrasensitive responses
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DOI：
10.1111/j.1742-4658.2005.04818.x
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发表时间：
2005-08-01
期刊：
影响因子：
5.4
通讯作者：
Herzel, H
中科院分区：
文献类型：
--
作者：
Legewie, S;Blüthgen, N;Herzel, H
超敏感反应在细胞信息传递中很常见，因为它们允许细胞以全有或全无的方式解码细胞外刺激。生化反应通常通过拟合Hill方程进行分析，并将估计的Hill系数作为灵敏度的度量。然而，如果所考虑的响应显著偏离最佳拟合的Hill方程，则该方法是不合适的。此外，希尔系数大于1并不一定意味着超灵敏的行为，如果基础激活是显着的。为了避免这些问题，我们提出了一个通用的方法，定量分析的灵敏度，相对放大图，这是基于代谢控制分析中定义的响应系数。为了在全局范围内（即在整个刺激范围内）量化灵敏度，我们引入了基于积分的相对放大系数。我们的相对放大方法可以很容易地扩展到单调递减，钟形或非饱和的响应。
Ultrasensitive responses are common in cellular information transfer because they allow cells to decode extracellular stimuli in an all-or-none manner. Biochemical responses are usually analyzed by fitting the Hill equation, and the estimated Hill coefficient is taken as a measure of sensitivity. However, this approach is not appropriate if the response under consideration significantly deviates from the best-fit Hill equation. In addition, Hill coefficients greater than unity do not necessarily imply ultrasensitive behaviour if basal activation is significant. In order to circumvent these problems we propose a general method for the quantitative analysis of sensitivity, the relative amplification plot, which is based on the response coefficient defined in metabolic control analysis. To quantify sensitivity globally (i.e. over the whole stimulus range) we introduce the integral-based relative amplification coefficient. Our relative amplification approach can easily be extended to monotonically decreasing, bell-shaped or nonsaturated responses.