Generalized concept of minimal cut sets in biochemical networks
Generalized concept of minimal cut sets in biochemical networks
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DOI：
10.1016/j.biosystems.2005.04.009
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发表时间：
2006-02-01
期刊：
影响因子：
1.6
通讯作者：
Klamt, S
中科院分区：
文献类型：
--
作者：
Klamt, S
最近，最小割集的概念被引入来研究生化反应网络中的结构脆弱性和识别敲除策略。最小割集（MCS）被定义为一个最小的反应集，其删除阻止了所选择的目标反应的操作。在这份报告中，MCSs的理论框架进行了细化和扩展，增加了显着的实用性。MCS现在被定义为抑制由删除任务指定的特定功能的结构干预（网络元素的移除）的最小（不可约）集合。删除任务明确地描述了要被抑制的通量模式（或功能）。它示出的MCS可以计算从一组目标模式，其中包括所有的基本模式，表现出的功能被攻击。由于删除任务可以指定几个布尔规则，MCS现在可以确定为各种各样的复杂删除问题，并可用于抑制非常特殊的通量模式。它还表明，反过来也是可能的：属于某个功能的基本模式可以从相应的MCS集计算。因此，基本模式和MCS呼叫被视为网络功能的双重表示，两者可以相互转换。此外，从集合论中已知的最小碰集存在很强的关系：MCS是目标模式集合的最小碰集，反之亦然。本文介绍的另一个概括是，MCS不需要局限于删除反应，它们还可能包含网络节点。根据扩展框架的MCSs，应用程序进行评估，操纵和设计代谢网络在硅片进行了讨论。(C)2005爱思唯尔爱尔兰有限公司保留所有权利。
Recently, the concept of minimal cut sets has been introduced for studying structural fragility and identifying knock-out strategies in biochemical reaction networks. A minimal cut set (MCS) has been defined as a minimal set of reactions whose removal blocks the operation of a chosen objective reaction. In this report the theoretical framework of MCSs is refined and extended increasing the practical applicability significantly. An MCS is now defined as a minimal (irreducible) set of structural interventions (removal of network elements) repressing a certain functionality specified by a deletion task. A deletion task describes unambiguously the flux patterns (or the functionality) to be repressed. It is shown that the MCSs can be Computed from the set of target modes, which comprises all elementary modes that exhibit the functionality to be attacked. Since a deletion task can be specified by several Boolean rules, MCSs can now be determined for a large variety of complex deletion problems and may be utilized for inhibiting very special flux patterns. It is additionally shown that the other way around is also possible: the elementary modes belonging to a certain functionality can be computed from the respective set of MCSs. Therefore, elementary modes and MCSs Call be seen as dual representations of network functions and both can be converted into each other. Moreover, there exist a strong relationship to minimal hitting sets known from set theory: the MCSs are the minimal hitting sets of the collection of target modes and vice versa. Another generalization introduced herein is that MCSs need not to be restricted to the removal of reactions they may also contain network nodes. In the light of the extended framework of MCSs, applications for assessing, manipulating, and designing metabolic networks in silico are discussed. (C) 2005 Elsevier Ireland Ltd. All rights reserved.