Michaelis-Menten曲线的均匀性检验及其在荧光共振能量转移数据中的应用
Homogeneity tests for Michaelis-Menten curves with application to fluorescence resonance energy transfer data
摘要：
共振能量转移方法广泛用于评价活细胞中的蛋白质相互作用和蛋白质构象变化。荧光共振能量转移（FRET）测量作为受体：供体比率的函数的能量转移，产生FRET饱和曲线。通过Michaelis-Menten动力学对这些曲线进行建模，可以通过两个参数进行表征，这两个参数用于评估两种蛋白质之间的表观亲和力，并在不同的实验条件下比较这种亲和力。为了减少采样变异性的影响，在相同的生物条件下生成饱和曲线的几个统计样本。在这里，我们研究三个程序，以确定是否在一个集合中的统计样本是同质的，在这个意义上，他们是从同一个回归模型中提取。从假设检验的角度来看，我们考虑了F检验和基于自举检验的程序。第三种方法从模型选择的角度分析问题，并使用赤池信息准则（AIC）。虽然我们只考虑了Michaelis-Menten模型，但所有的统计过程都适用于任何其他非线性回归模型。我们比较了性能的同质性测试方法在Monte Carlo研究，并通过分析在活细胞中的FRET饱和曲线的二聚体复合物的CXCR 4，一个七跨膜受体的G蛋白偶联受体家族。我们发现，F检验，自助程序和模型选择方法一般导致类似的结论，虽然AIC给出了最好的结果时，样本量小，而F检验和自助方法更适合于大样本。在实践中，所有三种方法都易于同时使用，并显示出一致性，有助于得出样品均匀性的结论。
英文摘要：
Resonance energy transfer methods are in wide use for evaluating protein-protein interactions and protein conformational changes in living cells. Fluorescence resonance energy transfer (FRET) measures energy transfer as a function of the acceptor:donor ratio, generating FRET saturation curves. Modeling these curves by Michaelis-Menten kinetics allows characterization by two parameters, which serve to evaluate apparent affinity between two proteins and to compare this affinity in different experimental conditions. To reduce the effect of sampling variability, several statistical samples of the saturation curve are generated in the same biological conditions. Here we study three procedures to determine whether statistical samples in a collection are homogeneous, in the sense that they are extracted from the same regression model. From the hypothesis testing viewpoint, we considered an F test and a procedure based on bootstrap resampling. The third method analyzed the problem from the model selection viewpoint, and used the Akaike information criterion (AIC). Although we only considered the Michaelis-Menten model, all statistical procedures would be applicable to any other nonlinear regression model. We compared the performance of the homogeneity testing methods in a Monte Carlo study and through analysis in living cells of FRET saturation curves for dimeric complexes of CXCR4, a seven-transmembrane receptor of the G protein-coupled receptor family. We show that the F test, the bootstrap procedure and the model selection method lead in general to similar conclusions, although AIC gave the best results when sample sizes were small, whereas the F test and the bootstrap method were more appropriate for large samples. In practice, all three methods are easy to use simultaneously and show consistency, facilitating conclusions on sample homogeneity.
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