Predicting Gene Essentiality Using Genome-Scale in Silico Models

Genome-scale metabolic models of organisms can be reconstructed using annotated genome sequence information, well-curated databases, and primary research literature. The metabolic reaction stoichiometry and other physicochemical factors are incorporated into the model, thus imposing constraints that represent restrictions on phenotypic behavior. Based on this premise, the theoretical capabilities of the metabolic network can be assessed by using a mathematical technique known as flux balance analysis (FBA). This modeling framework, also known as the constraint-based reconstruction and analysis approach, differs from other modeling strategies because it does not attempt to predict exact network behavior. Instead, this approach uses known constraints to separate the states that a system can achieve from those that it cannot. In recent years, this strategy has been employed to probe the metabolic capabilities of a number of organisms, to generate and test experimental hypotheses, and to predict accurately metabolic phenotypes and evolutionary outcomes. This chapter introduces the constraint-based modeling approach and focuses on its application to computationally predicting gene essentiality.