Integration of metabolome data with metabolic networks reveals reporter reactions.
Integration of metabolome data with metabolic networks reveals reporter reactions.
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代谢组数据与代谢网络的集成揭示了报告基因反应。
DOI：
10.1038/msb4100085
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发表时间：
2006
影响因子：
9.9
通讯作者：
Nielsen, Jens
中科院分区：
文献类型：
--
作者：
Cakir, Tunahan;Patil, Kiran Raosaheb;Onsan, Zeynep iIsen;Ulgen, Kutlu Ozergin;Kirdar, Betul;Nielsen, Jens
由于代谢网络的高度连通性以及酶调节、代谢物水平和通量之间固有的相互依赖性，解释定量代谢组数据是一项艰巨的任务。在这里，我们提出了一个假设驱动的算法，这些数据与代谢网络拓扑结构的整合。因此，该算法能够识别报告反应，其是在环境/遗传扰动后周围代谢物水平存在显著协调变化的反应。该算法的适用性证明了从酿酒酵母的数据。该算法包括基因组规模的酵母模型的预处理，使得模型内测量的代谢物的分数被增强，因此即使测量了完整代谢物组的一小部分，也可以映射与扰动相关的显著改变。通过将结果与转录组数据相结合，我们进一步表明，可以推断反应是否是分层或代谢调节的。据此，所报道的方法代表了通过代谢组和转录组数据的组合来映射代谢网络内的不同调控层的尝试。
Interpreting quantitative metabolome data is a difficult task owing to the high connectivity in metabolic networks and inherent interdependency between enzymatic regulation, metabolite levels and fluxes. Here we present a hypothesis-driven algorithm for the integration of such data with metabolic network topology. The algorithm thus enables identification of reporter reactions, which are reactions where there are significant coordinated changes in the level of surrounding metabolites following environmental/genetic perturbations. Applicability of the algorithm is demonstrated by using data from Saccharomyces cerevisiae. The algorithm includes preprocessing of a genome-scale yeast model such that the fraction of measured metabolites within the model is enhanced, and thus it is possible to map significant alterations associated with a perturbation even though a small fraction of the complete metabolome is measured. By combining the results with transcriptome data, we further show that it is possible to infer whether the reactions are hierarchically or metabolically regulated. Hereby, the reported approach represents an attempt to map different layers of regulation within metabolic networks through combination of metabolome and transcriptome data.