SBML Level 3 Package: Flux Balance Constraints ('fbc')

Abstract

Constraint based modeling is a widely accepted methodology used to analyze and study biological networks on both a small and whole organism (genome) scale. Typically these models are underdetermined and constraint based methods (e.g. linear, quadratic optimization) are used to optimize specific model properties. This is assumed to occur under a defined set of constraints (e.g. stoichiometric, metabolic) and bounds (e.g. thermodynamic, experimental and environmental) on the values that the solution fluxes can obtain. Perhaps the most well known (and widely used) analysis method is Flux Balance Analysis (FBA; Orth et al., 2010) which is performed on Genome Scale Reconstructions (GSR's; Oberhardt et al., 2009). Using FBA a target flux is optimized (e.g. maximizing a flux to biomass or minimizing ATP production) while other fluxes can be bounded to simulate a selected growth environment or specific metabolic state. As constraint based models are generally underdetermined, i.e. few or none of the kinetic rate equations and related parameters are known, it is crucial that a model definition includes the ability to define optimization parameters such as objective functions, flux bounds and constraints. Currently this is not possible in the Systems Biology Markup Language (SBML) Level 2 or Level 3 core specification (Hucka et al., 2011, 2003). The question of how to encode constraint based (also referred to as steady state or FBA) models in SBML is not new. However, advances in the methods used to construct genome scale constraint based models and the wider adoption of constraint based modeling in biotechnological/medical applications have led to a rapid increase in both the number of models being constructed and the tools used to analyze them. Faced with such growth, both in number and diversity, the need for a standardized data format for the definition, exchange and annotation of constraint based models has become critical. As the core model components (e.g. species, reactions, stoichiometry) can already be efficiently described in SBML (with its associated active community, software and tool support) the Flux Balance Constraints package aims to extend SBML Level 3 core by adding the elements necessary to encode current and future constraint based models.

Files

Additional details