Physics Institute, University of Freiburg, 79104 Freiburg, Germany.
Bioinformatics. 2009 Aug 1;25(15):1923-9. doi: 10.1093/bioinformatics/btp358. Epub 2009 Jun 8.
Mathematical description of biological reaction networks by differential equations leads to large models whose parameters are calibrated in order to optimally explain experimental data. Often only parts of the model can be observed directly. Given a model that sufficiently describes the measured data, it is important to infer how well model parameters are determined by the amount and quality of experimental data. This knowledge is essential for further investigation of model predictions. For this reason a major topic in modeling is identifiability analysis.
We suggest an approach that exploits the profile likelihood. It enables to detect structural non-identifiabilities, which manifest in functionally related model parameters. Furthermore, practical non-identifiabilities are detected, that might arise due to limited amount and quality of experimental data. Last but not least confidence intervals can be derived. The results are easy to interpret and can be used for experimental planning and for model reduction.
An implementation is freely available for MATLAB and the PottersWheel modeling toolbox at http://web.me.com/andreas.raue/profile/software.html.
Supplementary data are available at Bioinformatics online.
通过微分方程对生物反应网络进行数学描述会导致产生大型模型,这些模型的参数需要经过校准,以最佳地解释实验数据。通常情况下,模型的只有部分可以直接观察到。给定一个能够充分描述测量数据的模型,推断模型参数通过实验数据的数量和质量来确定的程度就变得非常重要。这些知识对于进一步研究模型预测至关重要。出于这个原因,建模中的一个主要主题是可识别性分析。
我们提出了一种利用似然函数轮廓的方法。它能够检测到结构上的不可识别性,这些不可识别性表现在功能相关的模型参数上。此外,还会检测到可能由于实验数据的数量和质量有限而产生的实际不可识别性。最后但并非最不重要的是,可以推导出置信区间。这些结果易于解释,可用于实验规划和模型简化。
MATLAB 以及 PottersWheel 建模工具包的实现可在 http://web.me.com/andreas.raue/profile/software.html 上免费获得。
补充数据可在 Bioinformatics 在线获得。