Analysis of Metabolic Subnetworks by Flux Cone Projection

Analysis of Metabolic Subnetworks by Flux Cone Projection
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DOI:
10.1186/1748-7188-7-17
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发表时间:
2012-05-29
影响因子:
1
通讯作者:
Bockmayr, Alexander
Bockmayr, Alexander
中科院分区:
生物学4区
文献类型:
--
作者:
Marashi, Sayed-Amir;David, Laszlo;Bockmayr, Alexander

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背景:在代谢网络的研究中,基本模式分析(EM)被证明是一种强大的基于约束的方法。然而,EM的枚举是一项艰巨的计算任务。此外,由于其数量庞大,EM不能简单地用作后续分析的输入。一种可能性是将分析限制在感兴趣的反应的子集。然而,分析一个孤立的子网络可能会导致发现不正确的EM,这不是原始网络的任何稳态通量分布的一部分。描述子网络中反应活性的理想集合是投射到感兴趣反应的所有EM的集合。最近,“基本通量模式”(EFP)的概念已经提出。每个EFP是支撑的子集(即,结果:我们引入了投影锥基本模式的概念。ProCEM集可以通过将通量锥投影到低维子空间上并枚举投影锥的极端射线来计算。与EFP相反,ProCEM不仅仅是一组反应,而是预测EM。我们还证明了一组EFP包括在一组ProCEM支持。最后,ProCEMS和EFP的研究生物networks.Conclusions的子结构进行了比较:我们介绍了ProCEMS的概念,并建议其用于分析的代谢网络的子结构,EM的集合不能计算。
Background: Analysis of elementary modes (EMs) is proven to be a powerful constraint-based method in the study of metabolic networks. However, enumeration of EMs is a hard computational task. Additionally, due to their large number, EMs cannot be simply used as an input for subsequent analysis. One possibility is to limit the analysis to a subset of interesting reactions. However, analysing an isolated subnetwork can result in finding incorrect EMs which are not part of any steady-state flux distribution of the original network. The ideal set to describe the reaction activity in a subnetwork would be the set of all EMs projected to the reactions of interest. Recently, the concept of "elementary flux patterns" (EFPs) has been proposed. Each EFP is a subset of the support (i.e., non-zero elements) of at least one EM.Results: We introduce the concept of ProCEMs (Projected Cone Elementary Modes). The ProCEM set can be computed by projecting the flux cone onto a lower-dimensional subspace and enumerating the extreme rays of the projected cone. In contrast to EFPs, ProCEMs are not merely a set of reactions, but projected EMs. We additionally prove that the set of EFPs is included in the set of ProCEM supports. Finally, ProCEMs and EFPs are compared for studying substructures of biological networks.Conclusions: We introduce the concept of ProCEMs and recommend its use for the analysis of substructures of metabolic networks for which the set of EMs cannot be computed.