Galvão Ferrarini Mariana, Ziska Irene, Andrade Ricardo, Julien-Laferrière Alice, Duchemin Louis, César Roberto Marcondes, Mary Arnaud, Vinga Susana, Sagot Marie-France
Laboratoire de Biométrie et Biologie Évolutive, UMR 5558, CNRS, Université de Lyon, Université Lyon 1, Villeurbanne, France.
Univ Lyon, INRAE, INSA-Lyon, BF2I, UMR 203, Villeurbanne, France.
Front Genet. 2022 Feb 21;13:815476. doi: 10.3389/fgene.2022.815476. eCollection 2022.
The increasing availability of metabolomic data and their analysis are improving the understanding of cellular mechanisms and how biological systems respond to different perturbations. Currently, there is a need for novel computational methods that facilitate the analysis and integration of increasing volume of available data. In this paper, we present Totoro a new constraint-based approach that integrates quantitative non-targeted metabolomic data of two different metabolic states into genome-wide metabolic models and predicts reactions that were most likely active during the transient state. We applied Totoro to real data of three different growth experiments (pulses of glucose, pyruvate, succinate) from and we were able to predict known active pathways and gather new insights on the different metabolisms related to each substrate. We used both the core and the iJO1366 models to demonstrate that our approach is applicable to both smaller and larger networks. Totoro is an open source method (available at https://gitlab.inria.fr/erable/totoro) suitable for any organism with an available metabolic model. It is implemented in C++ and depends on IBM CPLEX which is freely available for academic purposes.
代谢组学数据的可得性不断提高及其分析方法的发展,正增进我们对细胞机制以及生物系统如何响应不同扰动的理解。当前,需要新颖的计算方法来促进对日益增多的可用数据的分析与整合。在本文中,我们展示了Totoro,这是一种基于约束的新方法,它将两种不同代谢状态的定量非靶向代谢组学数据整合到全基因组代谢模型中,并预测在瞬态期间最可能活跃的反应。我们将Totoro应用于来自三个不同生长实验(葡萄糖、丙酮酸、琥珀酸脉冲实验)的真实数据,并且能够预测已知的活跃途径,并获得与每种底物相关的不同代谢的新见解。我们使用核心模型和iJO1366模型来证明我们的方法适用于较小和较大的网络。Totoro是一种开源方法(可在https://gitlab.inria.fr/erable/totoro获取),适用于任何具有可用代谢模型的生物体。它用C++实现,依赖于可免费用于学术目的的IBM CPLEX。