Figure 1. The philosophy of COnstraints-Based Reconstruction and Analysis.

(a) COnstraints-Based Reconstruction and Analysis (COBRA) of biological networks involves the creation of network models from a variety of biological data sources. The capabilities of the model are then assessed in the context of physical, chemical, regulatory, and omics constraints (Reproduced from Becker et al.¹⁷ with permission). (b) COBRA models are often derived from BiGG knowledgebases which are essentially 2-D annotations of the genome that relate metabolic activity to genomic loci. (left inset) In Escherichia coli, the glyceraldehyde-3-phosphate dehydrogenase (GAPD) activity can be provided by two isozymes (GapA or GapC); GapC is a heteromeric protein that requires genes from two genomic loci. The contents of a BiGG knowledgebase can be converted to a map (right) to facilitate visual interpretation. Or a mathematical modeling formalism to develop and explore hypotheses, such as a stoichiometric matrix (bottom) that can be used to explore mass flow through the network. (Modified reproduction from Reed et al.³³ with permission).