An ensemble evolutionary constraint-based approach to understand the emergence of metabolic phenotypes

作者：Damiani Chiara^*; Pescini Dario; Colombo Riccardo; Molinari Sara; Alberghina Lilia; Vanoni Marco; Mauri Giancarlo

来源：Natural Computing, 2014, 13(3): 321-331.

DOI：10.1007/s11047-014-9439-4

• Flux balance analysis
• Constraint-based modeling
• Genetic algorithm
• Metabolic network modeling
• Crabtree effect
• Randomized sampling

Constraint-based modeling is largely used in computational studies of metabolism. We propose here a novel approach that aims to identify ensembles of flux distributions that comply with one or more target phenotype(s). The methodology has been tested on a small-scale model of yeast energy metabolism. The target phenotypes describe the differential pattern of ethanol production and O-2 consumption observed in %26quot;Crabtree-positive%26quot; and %26quot;Crabtree-negative%26quot; yeasts in changing environment (i.e., when the upper limit of glucose uptake is varied). The ensembles were obtained either by selection among sampled flux distributions or by means of a search heuristic (genetic algorithm). The former approach provided indication about the probability to observe a given phenotype, but the resulting ensembles could not be unambiguously partitioned into %26quot;Crabtree-positive%26quot; and %26quot;Crabtree-negative%26quot; clusters. On the contrary well-separated clusters were obtained with the latter method. The cluster analysis further allowed identification of distinct groups within each target phenotype. The method may thus prove useful in characterizing the design principles underlying metabolic plasticity arising from evolving physio-pathological or developmental constraints.

• 出版日期2014-9