Agreement assessment of biochemical pathway models by structural analysis of their intersection

Abstract

In case of model development, it would be an advantage to assess the quality of available models looking for the best one or to find suitable parts of a published model to build a new one. The differences or contradictions in reconstructions can indicate the level of agreement between different authors about the topic of interest. The intersecting part of models can reveal also the differences in the scope of the models. Two pairs of models from BioCyc database were analyzed: 1) the Escherichia coli models ecol199310cyc and ecol316407cyc and 2) the Saccharomyces cerevisiae models iND750 and iLL672. The ModeRator software tool is used to compare models and generate their intersection model. The structural parameters of models are analyzed by the software BINESA. The study reveals very different parameters of the intersections of the pairs of the E. coli and the S. cerevisiae models. The models built by the same group of authors like in the case of E. coli is selected as an example of a high agreement between models and can be interpreted as a consensus part of two initial models. The intersection of the S. cerevisiae models demonstrates very different structural properties and the intersection model would not be able to function even after significant improvement. The structural analysis of the pairs of original models and their intersections is performed to determine which structural parameters can be used to determine a poor agreement between the pairs of models. It is concluded that an application of the automated comparison and intersection generation of two models can give a fast insight in the similarity of the models to find out the consensus level in modelling of metabolism of a particular organism. This approach can be used also to find similarities between the models of different organisms. Automation of intersection creation and structural analysis are enabling technologies of this approach.