title: Constraining the metabolic genotype-phenotype relationship using a phylogeny of in silico methods.
abstract: Reconstructed microbial metabolic networks facilitate a mechanistic description of the genotype-phenotype relationship through the deployment of constraint-based reconstruction and analysis (COBRA) methods. As reconstructed networks leverage genomic data for insight and phenotype prediction, the development of COBRA methods has accelerated following the advent of whole-genome sequencing. Here, we describe a phylogeny of COBRA methods that has rapidly evolved from the few early methods, such as flux balance analysis and elementary flux mode analysis, into a repertoire of more than 100 methods. These methods have enabled genome-scale analysis of microbial metabolism for numerous basic and applied uses, including antibiotic discovery, metabolic engineering and modelling of microbial community behaviour.
authors.affiliation: Department of Bioengineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, California                 92093-0412, USA.
authors.forename: Nathan E
authors.initials: NE
authors.lastname: Lewis
authors.forename: Harish
authors.initials: H
authors.lastname: Nagarajan
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Palsson
mesh_terms: D020635:Buchnera / Q000235:genetics / Q000378:metabolism; D003198:Computer Simulation; D004734:Energy Metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism*; D016680:Genome, Bacterial; D016681:Genome, Fungal; D005838:Genotype; D060847:Metabolic Engineering; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008954:Models, Biological; D010641:Phenotype