A priori analysis of metabolic flux identifiability from 13C-labeling data

A priori analysis of metabolic flux identifiability from 13C-labeling data
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DOI:
10.1002/bit.1142
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发表时间:
2001-09-20
影响因子:
3.8
通讯作者:
Grievink, J
Grievink, J
中科院分区:
工程技术2区
文献类型:
--
作者:
van Winden, WA;Heijnen, JJ;Grievink, J

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c -13标记技术被引入代谢工程领域,作为一种工具,用于确定使用“经典”通量平衡方法无法找到的通量。为了确定c -13标记实验是否允许识别所有通量,需要进行先验通量可识别性分析。在本文中,我们提出了一种基于最近引入的“消费者”概念的可识别性分析方法。该方法改进了以往的可辨识性方法,提供了一种基于构成网络的结构元素系统地约简代谢网络的方法,并利用隐函数定理解析地确定约简后网络中的通量对于各种类型的实际测量数据是否具有理论可辨识性。将该方法应用于实际的通量识别问题,既表明了该方法在得出关于可识别性的新的有趣结论方面的潜力,也表明了由于符号计算随着所研究系统的尺寸而快速增长而引起的实际限制。(C) 2001约翰威利父子公司生物工程学报,2009,31(2):559 - 564。
The C-13-labeling technique was introduced in the field of metabolic engineering as a tool for determining fluxes that could not be found using the 'classical' method of flux balancing. An a priori flux identifiability analysis is required in order to determine whether a C-13-labeling experiment allows the identification of all the fluxes. In this article, we propose a method for identifiability analysis that is based on the recently introduced 'cumomer' concept. The method improves upon previous identifiability methods in that it provides a way of systematically reducing the metabolic network on the basis of structural elements that constitute a network and to use the implicit function theorem to analytically determine whether the fluxes in the reduced network are theoretically identifiable for various types of real measurement data. Application of the method to a realistic flux identification problem shows both the potential of the method in yielding new, interesting conclusions regarding the identifiability and its practical limitations that are caused by the fact that symbolic calculations grow fast with the dimension of the studied system. (C) 2001 John Wiley & Sons, Inc. Biotechnol Bioeng 74: 505-516, 2001.