The application of flux balance analysis in systems biology
The application of flux balance analysis in systems biology
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DOI：
10.1002/wsbm.60
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发表时间：
2010-05-01
影响因子：
7.9
通讯作者：
Papin, Jason A.
中科院分区：
文献类型：
--
作者：
Gianchandani, Erwin P.;Chavali, Arvind K.;Papin, Jason A.
越来越多的基因组规模的细胞内生化网络重建正在产生。与这些化学计量模型相结合，已经开发了几种基于系统的方法来通过计算机模拟来探测这些重建。一种这样的方法，称为通量平衡分析（FBA），已有效地预测系统表型的形式通量通过反应网络。FBA采用线性规划（LP）策略来生成通量分布，该通量分布针对特定的“目标”进行优化，并受到一组基本的物理化学和热力学约束。虽然经典的FBA假设稳态条件下，近年来已经提出了几个扩展，以限制允许的通量分布，并使动态配置文件的表征，即使用最少的动力学信息。此外，FBA加上测量体内通量的技术，促进了计算和实验方法的整合，并允许追求合理的假设驱动的研究。最终，正如我们将在这篇综述中描述的那样，研究细胞内反应通量使我们能够了解网络结构和功能，并具有从代谢工程到药物发现的广泛应用。(C)John Wiley & Sons，Inc. WIRES系统生物医学2010 2 372-382
An increasing number of genome-scale reconstructions of intracellular biochemical networks are being generated. Coupled with these stoichiometric models, several systems-based approaches for probing these reconstructions in silico have been developed. One such approach, called flux balance analysis (FBA), has been effective at predicting systemic phenotypes in the form of fluxes through a reaction network. FBA employs a linear programming (LP) strategy to generate a flux distribution that is optimized toward a particular 'objective,' subject to a set of underlying physicochemical and thermodynamic constraints. Although classical FBA assumes steady-state conditions, several extensions have been proposed in recent years to constrain the allowable flux distributions and enable characterization of dynamic profiles even with minimal kinetic information. Furthermore, FBA coupled with techniques for measuring fluxes in vivo has facilitated integration of computational and experimental approaches, and is allowing pursuit of rational hypothesis-driven research. Ultimately, as we will describe in this review, studying intracellular reaction fluxes allows us to understand network structure and function and has broad applications ranging from metabolic engineering to drug discovery. (C) 2009 John Wiley & Sons, Inc. WIREs Syst Biol Med 2010 2 372-382