Paper detail

Model composition through model reduction: a combined model of CD95 and NF-κB signaling pathways

We propose a new approach to model composition, based on reducing several models to the same level of complexity and subsequent combining them together. Firstly, we suggest a set of model reduction tools that can be systematically applied to a given model. Secondly, we suggest a notion of a minimal complexity model. This model is the simplest one that can be obtained from the original model using these tools and still able to approximate experimental data. Thirdly, we propose a strategy for composing the reduced models together. Connection with the detailed model is preserved, which can be advantageous in some applications. A toolbox for model reduction and composition has been implemented as part of the BioUML software and tested on the example of integrating two previously published models of the CD95 (APO-1/Fas) signaling pathways. We show that the reduced models lead to the same dynamical behavior of observable species and the same predictions as in the precursor models. The composite model is able to recapitulate several experimental datasets which were used by the authors of the original models to calibrate them separately, but also has new dynamical properties.