The topology of metabolic isotope labeling networks.
The topology of metabolic isotope labeling networks.
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DOI：
10.1186/1471-2105-8-315
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发表时间：
2007-08-29
影响因子：
3
通讯作者：
Nöh K
中科院分区：
文献类型：
--
作者：
Weitzel M;Wiechert W;Nöh K
基于同位素标记实验（ILEs）的代谢通量分析（MFA）是一种广泛建立的测定代谢途径中通量的工具。同位素标记网络（iln）包含描述ILE中标记物质流动所需的所有基本信息。尽管最近的实验进展为高通量MFA、大型网络调查和精确统计方法铺平了道路，但这些发展仍然受到用于评估和设计ILEs的计算例程性能不佳的限制。在这种情况下，ILN拓扑的全局分析成为在所有所需计算过程中实现大加速因子的线索。利用图论的概念和算法研究了网络的拓扑结构，重点关注算法的加速问题。严格确定所有循环和同构子网，伴随着ILN连通性的全局分析。特别是，研究证明，iln总是分解成大量的小的强连接组件（scc），而且，许多这些scc之间存在天然的同构。所有提出的技术都是通用的，即它们不需要对网络结构、通量的双向性、测量配置或标签输入进行特殊假设。一般结果用一个实际相关的代谢网络举例说明，该网络描述了由10390个同位素体池组成的大肠杆菌的中心代谢。利用iln的拓扑特征可以显著提高所有通用的iln评估算法的速度。理论证明，并以大肠杆菌为例，与标准算法相比，实现了约1000的加速因子。这为适用于高吞吐量应用和大型iln的新型高性能算法打开了大门。此外，对于iln的全局拓扑分析首次允许全面描述和理解复杂网络中标签流的一般模式。这是一个宝贵的工具，为新的实验结构设计和测量数据的解释。
Metabolic Flux Analysis (MFA) based on isotope labeling experiments (ILEs) is a widely established tool for determining fluxes in metabolic pathways. Isotope labeling networks (ILNs) contain all essential information required to describe the flow of labeled material in an ILE. Whereas recent experimental progress paves the way for high-throughput MFA, large network investigations and exact statistical methods, these developments are still limited by the poor performance of computational routines used for the evaluation and design of ILEs. In this context, the global analysis of ILN topology turns out to be a clue for realizing large speedup factors in all required computational procedures. With a strong focus on the speedup of algorithms the topology of ILNs is investigated using graph theoretic concepts and algorithms. A rigorous determination of all cyclic and isomorphic subnetworks, accompanied by the global analysis of ILN connectivity is performed. Particularly, it is proven that ILNs always brake up into a large number of small strongly connected components (SCCs) and, moreover, there are natural isomorphisms between many of these SCCs. All presented techniques are universal, i.e. they do not require special assumptions on the network structure, bidirectionality of fluxes, measurement configuration, or label input. The general results are exemplified with a practically relevant metabolic network which describes the central metabolism of E. coli comprising 10390 isotopomer pools. Exploiting the topological features of ILNs leads to a significant speedup of all universal algorithms for ILE evaluation. It is proven in theory and exemplified with the E. coli example that a speedup factor of about 1000 compared to standard algorithms is achieved. This widely opens the door for new high performance algorithms suitable for high throughput applications and large ILNs. Moreover, for the first time the global topological analysis of ILNs allows to comprehensively describe and understand the general patterns of label flow in complex networks. This is an invaluable tool for the structural design of new experiments and the interpretation of measured data.
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影响因子：
7.2
作者：
Ratcliffe, RG;Shachar-Hill, Y
通讯作者：
Shachar-Hill, Y
影响因子：
3.2
作者：
Gombert, AK;dos Santos, MM;Nielsen, J
通讯作者：
Nielsen, J
DOI：
10.1046/j.1432-1327.2001.02126.x
发表时间：
2001-04-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
Maaheimo, H;Fiaux, J;Szyperski, T
通讯作者：
Szyperski, T
影响因子：
30.8
作者：
Fischer, E;Sauer, U
通讯作者：
Sauer, U
影响因子：
8.4
作者：
Noeh, Katharina;Wahl, Aljoscha;Wiechert, Wolfgang
通讯作者：
Wiechert, Wolfgang