Metabolic flux-based modularity using shortest retroactive distances.

Metabolic flux-based modularity using shortest retroactive distances.
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DOI:
10.1186/1752-0509-6-155
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发表时间:
2012-12-27
影响因子:
--
通讯作者:
Lee K
Lee K
中科院分区:
生物2区
文献类型:
--
作者:
Sridharan GV;Yi M;Hassoun S;Lee K

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基于图的模块性分析已经成为研究生物网络功能组织的重要工具。然而,很少有方法可以使用生物活性数据来研究网络模块性的状态依赖性变化。我们开发了一个加权方案,代谢通量数据的基础上,调整相互作用的距离在一个以反应为中心的图模型的代谢网络。加权方案与具有保存代谢周期的分层模块分配算法相结合,以检查细胞分化和酶抑制对脂肪细胞代谢的功能组织的影响。我们的分析发现,各种代谢状态之间的差异主要涉及脂肪酸合成和甘油生成中两个特定反应的分配。我们的分析还确定了反应之间的周期性相互作用,这些反应在代谢状态方面是稳健的,这表明可能存在协同调节。基于反应对之间的周期性相互作用距离的比较表明,脂肪细胞代谢的模块化组织相对于酶的抑制是稳定的,而一个主要的生理变化,如细胞分化导致更实质性的重组。两者合计,我们的研究结果支持的概念,即网络模块化的影响,网络的组件的连接,以及连接的相对参与。
Graph-based modularity analysis has emerged as an important tool to study the functional organization of biological networks. However, few methods are available to study state-dependent changes in network modularity using biological activity data. We develop a weighting scheme, based on metabolic flux data, to adjust the interaction distances in a reaction-centric graph model of a metabolic network. The weighting scheme was combined with a hierarchical module assignment algorithm featuring the preservation of metabolic cycles to examine the effects of cellular differentiation and enzyme inhibitions on the functional organization of adipocyte metabolism. Our analysis found that the differences between various metabolic states primarily involved the assignment of two specific reactions in fatty acid synthesis and glycerogenesis. Our analysis also identified cyclical interactions between reactions that are robust with respect to metabolic state, suggesting possible co-regulation. Comparisons based on cyclical interaction distances between reaction pairs suggest that the modular organization of adipocyte metabolism is stable with respect to the inhibition of an enzyme, whereas a major physiological change such as cellular differentiation leads to a more substantial reorganization. Taken together, our results support the notion that network modularity is influenced by both the connectivity of the network’s components as well as the relative engagements of the connections.
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