Quantitative refinement of reaction models

One approach to modelling complex biological systems is to start from an abstract representation of the biological process and then to incorporate more details regarding its reactions or reactants through an iterative refinement process. The refinement should be done so as to ensure the preservation of the numerical properties of the model, such as its numerical fit and validation. Such approaches are well established in software engineering: starting from a formal specification of the system, one refines it step-by-step towards an implementation that is guaranteed to satisfy a number of logical properties. We introduce here the concepts of (quantitative) data refinement and process refinement of a biomolecular, reaction-based model. We choose as a case study a recently proposed model for the heat shock response and refine it to include some details of its acetylation-induced control. Although the refinement process produces a substantial increase in the number of kinetic parameters and variables, the methodology we propose preserves all the numerical properties of the model with a minimal computational effort.