Detection of stoichiometric inconsistencies in biomolecular models
Detection of stoichiometric inconsistencies in biomolecular models
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DOI：
10.1093/bioinformatics/btn425
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发表时间：
2008-10-01
期刊：
影响因子：
5.8
通讯作者：
Fell, David A.
中科院分区：
文献类型：
--
作者：
Gevorgyan, Albert;Poolman, Mark G.;Fell, David A.
动机：代谢建模为生化网络的系统级分析提供了严格的数学基础。然而，不断增长的规模的代谢模型可能会导致严重的问题，在其建设和验证。在这项工作中，我们描述了一个相对较差的调查类型的建模错误，称为化学计量不一致。这些错误是由反应化学计量的不正确定义引起的，并导致任何有效的代谢模型都要满足的两个基本物理约束之间的冲突：所有代谢物分子量的正性和所有相互转化中的质量守恒。我们介绍了化学计量不一致，不一致的净化学计量，不正确定义的生物分子网络的基本泄漏模式和其他重要的基本性质。算法描述了一个模型的化学计量的一致性，检测不保守的代谢物和不一致的最小净化学计量的验证。这些算法的有效解决的不一致性和输入错误的检测的有用性证明在已发表的基因组规模的代谢模型的酿酒酵母和无乳链球菌构建使用KEGG数据库之一。
Motivation: Metabolic modelling provides a mathematically rigorous basis for system-level analysis of biochemical networks. However, the growing sizes of metabolic models can lead to serious problems in their construction and validation. In this work, we describe a relatively poorly investigated type of modelling error, called stoichiometric inconsistencies. These errors are caused by incorrect definitions of reaction stoichiometries and result in conflicts between two fundamental physical constraints to be satisfied by any valid metabolic model: positivity of molecular masses of all metabolites and mass conservation in all interconversions.Results: We introduce formal definitions of stoichiometric inconsistencies, inconsistent net stoichiometries, elementary leakage modes and other important fundamental properties of incorrectly defined biomolecular networks. Algorithms are described for the verification of stoichiometric consistency of a model, detection of unconserved metabolites and inconsistent minimal net stoichiometries. The usefulness of these algorithms for effective resolving of inconsistencies and for detection of input errors is demonstrated on a published genome-scale metabolic model of Saccharomyces cerevisiae and one of Streptococcus agalactiae constructed using the KEGG database.