Phenotype

In silico

Evolutionary biology

Biology

Phylogenetics

Gene

Metabolic network

Genome

Flux balance analysis

Whole genome sequencing

Computational biology

Genetics

Nature Reviews Microbiology

Modelling of metabolic networks has facilitated genome-scale analysis of microbial metabolism for both basic and applied uses. Here, Palsson and colleagues describe the ever-growing 'phylogeny' of constraint-based reconstruction and analysis (COBRA) approaches used for modelling numerous aspects of microbial life. 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.

Constraining the metabolic genotype–phenotype relationship using a phylogeny of in silico methods