Totoro: Identifying Active Reactions During the Transient State for Metabolic Perturbations

Author(s)

Galvao Ferrarini, Mariana ; Ziska, Irene ; Andrade, Ricardo ; Julien-Laferriere, Alice ; Duchemin, Louis ; Cesar, Roberto Marcondes ; Mary, Arnaud ; Vinga, Susana ; Sagot, Marie-France

• Document type: Journal article
• Source: FRONTIERS IN GENETICS; v. 13, p. 12-pg., 2022-02-21.

Abstract

Motivation: 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.& nbsp;Results: 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 Escherichia coli 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 E. coli core and the iJO1366 models to demonstrate that our approach is applicable to both smaller and larger networks.& nbsp;Availability: Totoro is an open source method (available at ) 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. (AU)

• FAPESP's process: 15/22308-2 - Intermediate representations in Computational Science for knowledge discovery
• Grantee: Roberto Marcondes Cesar Junior
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/13430-9 - Enumerating multidimensional metabolic stories: models and methods
• Grantee: Ricardo Luiz de Andrade Abrantes
• Support Opportunities: Scholarships in Brazil - Post-Doctoral