Flux analysis of the Trypanosoma brucei glycolysis based on a multi-objective criteria bioinformatic approach, Advances in Bioinfromatics, 2012, in press. International conference with published acts
Résumé
Trypanosoma brucei is a protozoan parasite of major of interest to discover new genes for drug targets. This parasite alternates its life cycle between the mammal host(s) (bloodstream form) and the insect vector (procyclic form), with two divergent glucose metabolism amenable to in vitro culture. While the metabolic network of the bloodstream forms has been well characterized, the flux distribution between the different branches of the glucose metabolic network in the procyclic form has not been addressed so far. We present a computational analysis (called Metaboflux) that exploits the metabolic topology of the procyclic form, and allow the incorporation of multi-purpose experimental data to increase the biological relevance of the model. The alternatives resulting from the structural complexity of networks are formulated as an optimization problem solved by a metaheuristic where experimental data are modeled in a multi-objective function. Our results show that the current metabolic model is in agreement with experimental data and confirm the observed high metabolic flexibility of glucose metabolism. In addition, Metaboflux offers a rational explanation for the high flexibility in the ratio between final products from glucose metabolism, i.e. flux redistribution through the malic enzyme steps. Metaboflux is freely available at http://www.cbib.u-bordeaux2.fr/metaboflux.
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