OpenFLUX: efficient modelling software for 13C-based metabolic flux analysis.
OpenFLUX: efficient modelling software for 13C-based metabolic flux analysis.
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DOI：
10.1186/1475-2859-8-25
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发表时间：
2009-05-01
影响因子：
6.4
通讯作者：
Krömer JO
中科院分区：
文献类型：
--
作者：
Quek LE;Wittmann C;Nielsen LK;Krömer JO
代谢通量的定量分析，即体内细胞内酶和代谢途径的活性，为系统生物学和代谢工程中的生物系统提供了关键信息。它基于一种综合的方法，包括(1)在13C底物上进行示踪剂培养，(2)用质谱仪进行13C标记分析，以及(3)为实验设计、数据处理、通量计算和统计建立数学模型。虽然培养和分析部分相当先进，但在代谢通量研究的所有建模方面缺乏适当的建模软件解决方案限制了代谢通量分析的应用。我们开发了OpenFLUX作为一个用户友好的、但灵活的软件应用程序，用于小规模和大规模的13C代谢通量分析。该应用程序基于新的基本代谢物单元(EMU)框架，显著提高了通量计算的计算速度。通过在电子表格中定义的代谢反应网络的简单表示法，OpenFLUX解析器自动生成可读的代谢物和同位素平衡，从而极大地促进了模型的创建。该模型可用于实验设计、参数估计和灵敏度分析，可以使用内置的基于梯度的搜索或蒙特卡罗算法，也可以使用用户定义的算法。以包含71个反应、8个自由通量参数和10种代谢物的质量同位异体分布的微生物通量研究为例，OpenFLUX允许从包含代谢反应和碳转移机制的Excel文件自动编译基于EMU的模型，显示其用户友好性。它可靠地复制了公布的数据，并迅速找到了所研究网络的最佳流量分布(<；20秒)。我们开发了一种快速、准确的应用程序来执行稳态13C代谢通量分析。OpenFLUX将有力地促进和加强代谢流量研究的设计、计算和解释。通过提供开源软件，我们希望它将随着通量组学领域的快速发展而发展。
The quantitative analysis of metabolic fluxes, i.e., in vivo activities of intracellular enzymes and pathways, provides key information on biological systems in systems biology and metabolic engineering. It is based on a comprehensive approach combining (i) tracer cultivation on 13C substrates, (ii) 13C labelling analysis by mass spectrometry and (iii) mathematical modelling for experimental design, data processing, flux calculation and statistics. Whereas the cultivation and the analytical part is fairly advanced, a lack of appropriate modelling software solutions for all modelling aspects in flux studies is limiting the application of metabolic flux analysis. We have developed OpenFLUX as a user friendly, yet flexible software application for small and large scale 13C metabolic flux analysis. The application is based on the new Elementary Metabolite Unit (EMU) framework, significantly enhancing computation speed for flux calculation. From simple notation of metabolic reaction networks defined in a spreadsheet, the OpenFLUX parser automatically generates MATLAB-readable metabolite and isotopomer balances, thus strongly facilitating model creation. The model can be used to perform experimental design, parameter estimation and sensitivity analysis either using the built-in gradient-based search or Monte Carlo algorithms or in user-defined algorithms. Exemplified for a microbial flux study with 71 reactions, 8 free flux parameters and mass isotopomer distribution of 10 metabolites, OpenFLUX allowed to automatically compile the EMU-based model from an Excel file containing metabolic reactions and carbon transfer mechanisms, showing it's user-friendliness. It reliably reproduced the published data and optimum flux distributions for the network under study were found quickly (<20 sec). We have developed a fast, accurate application to perform steady-state 13C metabolic flux analysis. OpenFLUX will strongly facilitate and enhance the design, calculation and interpretation of metabolic flux studies. By providing the software open source, we hope it will evolve with the rapidly growing field of fluxomics.
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影响因子：
8.4
作者：
Antoniewicz, Maciek R.;Kraynie, David F.;Stephanopoulos, Gregory
通讯作者：
Stephanopoulos, Gregory
DOI：
10.1111/j.1432-1033.1995.tb20829.x
发表时间：
1995-09-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
SZYPERSKI, T
通讯作者：
SZYPERSKI, T
影响因子：
3.8
作者：
van Winden, WA;van Gulik, WM;Heijnen, JJ
通讯作者：
Heijnen, JJ
影响因子：
8.4
作者：
Suthers, Patrick F.;Burgard, Anthony P.;Maranas, Costas D.
通讯作者：
Maranas, Costas D.
影响因子：
4.4
作者：
Becker, J;Klopprogge, C;Wittmann, C
通讯作者：
Wittmann, C