Computational Methods for Quantitative Submodel Comparison

Comparing alternative models for a given biochemical system is in general a very difficult problem: the models may focus on different aspects of the same system and may consist of very different species and reactions. The numerical setups of the models also play a crucial role in the quantitative comparison. When the alternative designs are submodels of a reference model, e.g. knockdown mutants of a model, the problem of comparing them becomes simpler: they all have very similar, although not identical, underlying reaction networks, and the biological constraints are given by the ones in the reference model. In the first part of our study we review several known methods for model decomposition and for quantitative comparison of submodels. In the second part of the paper, we consider as a case study the eukaryotic heat shock response, an evolutionary well conserved defence mechanism against the accumulation of