Analysis on relationship between extreme pathways and correlated reaction sets.
Analysis on relationship between extreme pathways and correlated reaction sets.
复制标题
极端路径与相关反应集关系分析
DOI：
10.1186/1471-2105-10-s1-s58
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发表时间：
2009-01-30
影响因子：
3
通讯作者：
Wang F
中科院分区：
文献类型：
--
作者：
Xi Y;Chen YP;Cao M;Wang W;Wang F
基于约束的重建基因组规模的代谢网络建模已成功地应用于几种微生物。在基于约束的建模中，为了表征所有允许的表型，定义了基于网络的路径，例如极端路径和基本通量模式。然而，随着代谢网络规模的增加，极端途径和基本通量模式的数量呈指数增长。均匀随机抽样在一定程度上解决了这个问题，以研究可用表型的内容。在均匀随机抽样后，相关的反应集可以通过来自样本表型的反应之间的依赖性来识别。本文研究了极端途径与相关反应集之间的关系。鉴定了E.大肠杆菌核心、红细胞和酿酒酵母代谢网络。对于前两种代谢网络，列举了所有极端途径。对于酿酒酵母代谢网络，由于其规模较大，我们通过对整个极端路径空间进行采样，得到一组极端路径。在大多数情况下，极端路径以“全部或无”的方式覆盖相关反应集，这意味着相关反应集中的所有反应或无反应被某个极端路径使用。在极少数情况下，除了“全或无”的方式，相关的反应集可以通过具有相关功能的几个极端途径的组合来完全覆盖，这可以带来冗余和灵活性，以提高细胞的存活率。总之，在同一相关反应集中，极端途径在反应的使用上表现出很强的互补关系。极端途径和相关反应集都是从代谢网络的拓扑信息中得到的。相关反应集和极端途径之间的密切关系表明了一种可能的机制：极端途径作为一个可控单元，由其相应的相关反应集调节，相关反应集进一步由生物体的调节网络调节。
Constraint-based modeling of reconstructed genome-scale metabolic networks has been successfully applied on several microorganisms. In constraint-based modeling, in order to characterize all allowable phenotypes, network-based pathways, such as extreme pathways and elementary flux modes, are defined. However, as the scale of metabolic network rises, the number of extreme pathways and elementary flux modes increases exponentially. Uniform random sampling solves this problem to some extent to study the contents of the available phenotypes. After uniform random sampling, correlated reaction sets can be identified by the dependencies between reactions derived from sample phenotypes. In this paper, we study the relationship between extreme pathways and correlated reaction sets. Correlated reaction sets are identified for E. coli core, red blood cell and Saccharomyces cerevisiae metabolic networks respectively. All extreme pathways are enumerated for the former two metabolic networks. As for Saccharomyces cerevisiae metabolic network, because of the large scale, we get a set of extreme pathways by sampling the whole extreme pathway space. In most cases, an extreme pathway covers a correlated reaction set in an 'all or none' manner, which means either all reactions in a correlated reaction set or none is used by some extreme pathway. In rare cases, besides the 'all or none' manner, a correlated reaction set may be fully covered by combination of a few extreme pathways with related function, which may bring redundancy and flexibility to improve the survivability of a cell. In a word, extreme pathways show strong complementary relationship on usage of reactions in the same correlated reaction set. Both extreme pathways and correlated reaction sets are derived from the topology information of metabolic networks. The strong relationship between correlated reaction sets and extreme pathways suggests a possible mechanism: as a controllable unit, an extreme pathway is regulated by its corresponding correlated reaction sets, and a correlated reaction set is further regulated by the organism's regulatory network.