Global dynamic optimization approach to predict activation in metabolic pathways

BMC Systems Biology

Julio R Banga¹  Eva Balsa-Canto¹  Edda Klipp²  Gundián M de Hijas-Liste¹ 

[1] Bioprocess Engineering Group, Spanish National Research Council, IIM-CSIC, C/Eduardo Cabello 6, 36208 Vigo, Spain;Theoretical Biophysics, Humboldt-Universität zu Berlin, Invalidenstr. 42, 10115 Berlin, Germany

关键词: Gene expression;    Metabolic pathways;    Pareto optimality;    Multi-objective optimization;    Global optimization;    Dynamic optimization;   

Others  :  1141556
DOI  :  10.1186/1752-0509-8-1

 received in 2013-02-04, accepted in 2013-12-20,  发布年份 2014

【 摘 要 】

Background

During the last decade, a number of authors have shown that the genetic regulation of metabolic networks may follow optimality principles. Optimal control theory has been succesfully used to compute optimal enzyme profiles considering simple metabolic pathways. However, applying this optimal control framework to more general networks (e.g. branched networks, or networks incorporating enzyme production dynamics) yields problems that are analytically intractable and/or numerically very challenging. Further, these previous studies have only considered a single-objective framework.

Results

In this work we consider a more general multi-objective formulation and we present solutions based on recent developments in global dynamic optimization techniques. We illustrate the performance and capabilities of these techniques considering two sets of problems. First, we consider a set of single-objective examples of increasing complexity taken from the recent literature. We analyze the multimodal character of the associated non linear optimization problems, and we also evaluate different global optimization approaches in terms of numerical robustness, efficiency and scalability. Second, we consider generalized multi-objective formulations for several examples, and we show how this framework results in more biologically meaningful results.

Conclusions

The proposed strategy was used to solve a set of single-objective case studies related to unbranched and branched metabolic networks of different levels of complexity. All problems were successfully solved in reasonable computation times with our global dynamic optimization approach, reaching solutions which were comparable or better than those reported in previous literature. Further, we considered, for the first time, multi-objective formulations, illustrating how activation in metabolic pathways can be explained in terms of the best trade-offs between conflicting objectives. This new methodology can be applied to metabolic networks with arbitrary topologies, non-linear dynamics and constraints.

【 授权许可】

   
2014 de Hijas-Liste et al.; licensee BioMed Central Ltd.

【 图 表 】

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