Identification of Conserved Moieties in Metabolic Networks by Graph Theoretical Analysis of Atom Transition Networks.
Identification of Conserved Moieties in Metabolic Networks by Graph Theoretical Analysis of Atom Transition Networks.
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DOI：
10.1371/journal.pcbi.1004999
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发表时间：
2016-11
影响因子：
4.3
通讯作者：
Fleming RM
中科院分区：
文献类型：
--
作者：
Haraldsdóttir HS;Fleming RM
保守部分是在代谢网络的所有反应中保持完整的原子团。保守部分的鉴定提供了深入了解代谢网络的结构和功能，并促进代谢建模。所有的基团保守关系都可以表示为化学计量矩阵左零空间中的非负整数向量。存在仅基于反应化学计量来计算这样的向量的算法，但是它们的计算复杂性限制了它们对相对小的代谢网络的应用。此外，现有算法返回的向量一般不代表具有定义的原子结构的特定部分的保守性。在这里，我们表明，保守的部分的识别需要数据的反应原子映射除了化学计量。我们提出了一种新的方法来确定保守的部分代谢网络的图论分析其基础的原子过渡网络。我们的方法返回属于每个保守部分的确切原子群以及化学计量矩阵的左零空间中的相应向量。它可以实现为多项式时间算法的流水线。我们的实现在一个具有4,000多个质量平衡反应的代谢网络上在5分钟内完成。该方法的可扩展性，使现有的应用程序的部分保守关系的基因组规模的代谢网络。我们还给出了新的应用程序的例子，通过阐明保守部分的原子结构成为可能。保守部分在代谢网络的内部反应中在代谢物之间转移，但不合成、降解或与环境交换。因此，代谢网络中保守部分的总量随时间恒定。共有保守部分的代谢物具有相互依赖的浓度，因为它们的总量是恒定的。保守部分的识别结果在一个简洁的描述代谢网络中的所有浓度依赖性。识别保守部分的问题以前已经在代谢反应的化学计量学方面制定。基于此公式的方法对于大型网络是计算上难以处理的。我们表明，反应化学计量单独提供的信息不足，以确定保守的部分。通过首先将额外的数据的原子在代谢反应中的命运，我们开发和实施了一个计算上易于处理的算法，以确定保守的部分和它们的原子结构。
Conserved moieties are groups of atoms that remain intact in all reactions of a metabolic network. Identification of conserved moieties gives insight into the structure and function of metabolic networks and facilitates metabolic modelling. All moiety conservation relations can be represented as nonnegative integer vectors in the left null space of the stoichiometric matrix corresponding to a biochemical network. Algorithms exist to compute such vectors based only on reaction stoichiometry but their computational complexity has limited their application to relatively small metabolic networks. Moreover, the vectors returned by existing algorithms do not, in general, represent conservation of a specific moiety with a defined atomic structure. Here, we show that identification of conserved moieties requires data on reaction atom mappings in addition to stoichiometry. We present a novel method to identify conserved moieties in metabolic networks by graph theoretical analysis of their underlying atom transition networks. Our method returns the exact group of atoms belonging to each conserved moiety as well as the corresponding vector in the left null space of the stoichiometric matrix. It can be implemented as a pipeline of polynomial time algorithms. Our implementation completes in under five minutes on a metabolic network with more than 4,000 mass balanced reactions. The scalability of the method enables extension of existing applications for moiety conservation relations to genome-scale metabolic networks. We also give examples of new applications made possible by elucidating the atomic structure of conserved moieties. Conserved moieties are transferred between metabolites in internal reactions of a metabolic network but are not synthesised, degraded or exchanged with the environment. The total amount of a conserved moiety in the metabolic network is therefore constant over time. Metabolites that share a conserved moiety have interdependent concentrations because their total amount is constant. Identification of conserved moieties results in a concise description of all concentration dependencies in a metabolic network. The problem of identifying conserved moieties has previously been formulated in terms of the stoichiometry of metabolic reactions. Methods based on this formulation are computationally intractable for large networks. We show that reaction stoichiometry alone gives insufficient information to identify conserved moieties. By first incorporating additional data on the fate of atoms in metabolic reactions, we developed and implemented a computationally tractable algorithm to identify conserved moieties and their atomic structure.
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