Laboratoire de Recherche en Informatique, Université Paris-Sud, CNRS UMR 8623 and INRIA Saclay, Orsay, France ; SysDiag UMR3145 CNRS/Bio-Rad Parc Euromédecine, Montpellier, France.
PLoS One. 2013 Oct 29;8(10):e76143. doi: 10.1371/journal.pone.0076143. eCollection 2013.
Metabolic network analysis is an important step for the functional understanding of biological systems. In these networks, enzymes are made of one or more functional domains often involved in different catalytic activities. Elementary flux mode (EFM) analysis is a method of choice for the topological studies of these enzymatic networks. In this article, we propose to use an EFM approach on networks that encompass available knowledge on structure-function. We introduce a new method that allows to represent the metabolic networks as functional domain networks and provides an application of the algorithm for computing elementary flux modes to analyse them. Any EFM that can be represented using the classical representation can be represented using our functional domain network representation but the fine-grained feature of functional domain networks allows to highlight new connections in EFMs. This methodology is applied to the tricarboxylic acid cycle (TCA cycle) of Bacillus subtilis, and compared to the classical analyses. This new method of analysis of the functional domain network reveals that a specific inhibition on the second domain of the lipoamide dehydrogenase (pdhD) component of pyruvate dehydrogenase complex leads to the loss of all fluxes. Such conclusion was not predictable in the classical approach.
代谢网络分析是理解生物系统功能的重要步骤。在这些网络中，酶由一个或多个功能域组成，这些功能域通常涉及不同的催化活性。基本通量模式 (EFM) 分析是对这些酶网络进行拓扑研究的首选方法。在本文中，我们提出在包含结构-功能相关知识的网络上使用 EFM 方法。我们引入了一种新方法，可以将代谢网络表示为功能域网络，并提供了一种用于计算基本通量模式以分析它们的算法应用。任何可以使用经典表示表示的 EFM 都可以使用我们的功能域网络表示来表示，但是功能域网络的细粒度特征允许突出 EFM 中的新连接。该方法学应用于枯草芽孢杆菌的三羧酸循环 (TCA 循环)，并与经典分析进行了比较。功能域网络的这种新分析方法表明，对丙酮酸脱氢酶复合物中脂酰脱氢酶 (pdhD) 组件的第二个结构域的特定抑制会导致所有通量的丧失。这种结论在经典方法中是不可预测的。
