Iterative Multi Level Calibration of Metabolic Networks

Author(s): Max Conway, Claudio Angione, Pietro Liò.

Journal Name:Current Bioinformatics

Volume 11 , Issue 1 , 2016

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Abstract:

Frameworks for metabolic engineering have been successfully applied in combination with pre- and post-processing algorithms on genome-wide metabolic models. However, genetic engineering methods with a particular focus on understanding results from multiple perspectives and combining automated and human design are still lacking. To this end, we adopt a multi-objective genetic design technique to find the optimal gene expression levels in genome-scale metabolic reconstructions. Then, we analyse the optimized network by introducing a new multi-omic, multi-level post-processing and visualization procedure, Metabex, which uses Cytoscape for network visualization. These two components are connected together to form a feedback loop that establishes a continual process of machine optimization and human analysis and guidance. To benchmark our framework, we optimize two species of Geobacter for electricity production and biomass synthesis; we achieve increases in electricity production for only a slight decrease in biomass. Many regulatory strategies contributed to this value, locally and globally. For instance, a direct, local strategy was a down-regulation of Cytochrome C Oxidase, while there was simultaneously a global reduction in cofactor and prosthetic group biosynthesis. Finally, we discuss multiple applications of our tool, including model exploration, model engineering, comparative modelling, meta-analysis and model refinement.

Keywords: Meta-analysis, gene expression engineering, multi-scale model, metabolic network exploration.

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Article Details

VOLUME: 11
ISSUE: 1
Year: 2016
Page: [93 - 105]
Pages: 13
DOI: 10.2174/1574893611666151203222505