Department of Chemical and Biomolecular Engineering, National University of Singapore, Blk E5, 4 Engineering Drive 4, #02-16, Singapore 117576, Singapore.
J Biotechnol. 2010 Sep 1;149(3):132-40. doi: 10.1016/j.jbiotec.2010.02.019. Epub 2010 Mar 1.
Mathematical modeling has become an integral component in biotechnology, in which these models are frequently used to design and optimize bioprocesses. Canonical models, like power-laws within the Biochemical Systems Theory, offer numerous mathematical and numerical advantages, including built-in flexibility to simulate general nonlinear behavior. The construction of such models relies on the estimation of unknown case-specific model parameters by way of experimental data fitting, also known as inverse modeling. Despite the large number of publications on this topic, this task remains the bottleneck in canonical modeling of biochemical systems. The focus of this paper concerns with the question of identifiability of power-law models from dynamic data, that is, whether the parameter values can be uniquely and accurately identified from time-series data. Existing and newly developed parameter identifiability methods were applied to two power-law models of biochemical systems, and the results pointed to the lack of parametric identifiability as the root cause of the difficulty faced in the inverse modeling. Despite the focus on power-law models, the analyses and conclusions are extendable to other canonical models, and the issue of parameter identifiability is expected to be a common problem in biochemical system modeling.
数学建模已经成为生物技术不可或缺的一部分,这些模型经常被用于设计和优化生物工艺。在生物化学系统理论中,典范模型(如幂律模型)具有许多数学和数值上的优势,包括模拟一般非线性行为的内置灵活性。这些模型的构建依赖于通过实验数据拟合(也称为逆建模)来估计未知的特定于案例的模型参数。尽管关于这个主题的出版物很多,但这个任务仍然是生物化学系统典范建模的瓶颈。本文关注的问题是从动态数据中确定幂律模型的可识别性,也就是说,参数值是否可以从时间序列数据中唯一和准确地识别。现有的和新开发的参数可识别性方法被应用于两个生物化学系统的幂律模型,结果表明参数不可识别是逆建模中面临困难的根本原因。尽管本文重点关注幂律模型,但分析和结论可以扩展到其他典范模型,并且参数可识别性问题预计将是生物化学系统建模中的一个常见问题。