The fact that the same kind of formalism is used during the whole model refinement process, helps the creation of more straightforward methods for automatic mapping and validation of the models.
Additional attributes and details can be added during the iterative model refinement process to reflect new biological information or in vitro context.
The model, on the other hand, following step-wise methods determines the parameters through an optimization procedure (with respect to the residual sum of squares at each step in the model) and the model refinement process takes care of possible combinations of parameter inputs thereby choosing the most influential parameters and corresponding functional forms.
Having a new general framework was needed in part to reduce unnecessary, cross-model redundancies between different candidate CELLS during analogue refinement, and facilitate an iterative model refinement process capable of automated cross-model validation.
In steps 2 and 3 of the model refinement process, we assessed and improved the model by comparing its predictions to experimentally determined gene essentialities, derived from the ADP1 mutant collection [ 8] (see Figure 1).
On the other hand, a key advantage of the approach built into ISEA and its framework are their adaptability for inclusion of additional attributes and details through an iterative model refinement process [ 8].
During model refinement, linear and nonlinear processes and elimination pathways were included.
A framework for the development of complex systems models, independent of either domain or modeling techniques, termed the CoSMoS (Complex System Modeling and Simulation) process, has since evolved comprising an iterative process of model refinement and implementation.
Nearly twenty such models have been built so far [ 2], typically through extensive curation work, and, for some of them, through iterative refinement processes where models were progressively improved by comparison with experimental datasets [ 4].
MDD is an approach for software development that puts a particular emphasis upon making models the primary development artifacts and upon subjecting such models to a refinement process by using automatic transformations until a running system is obtained.
