Comparing Metabolic Pathways through Potential Fluxes: a Selective Opening Approach

In our previous work we developed CoMeta, a tool for comparing metabolic pathways of different organisms, using the KEGG database as data source. The similarity measure adopted combines homology of reactions and functional aspects of the pathways. The latter are captured by T-invariants in the Petri net representation, which correspond to potential fluxes in the pathways. A Petri net can model a metabolic pathway of an organism either in isolation, focussing on its internal behaviour (isolated net), or as an interactive subsystem of the full metabolic network (open net). Modelling a pathway as an isolated net normally works fine for comparison purposes, but unsatisfactory results can arise as it supplies a partial view on internal fluxes. A representation as an open net makes additional information available, but the choice of the interactions of the pathway with the environment is non-trivial. Considering all possible interactions with the environment (an information automatically retrieved from KEGG) is not appropriate. Some interactions may add noise to the model, the size of invariants bases grows up to an order of magnitude and the comparison results might be less precise than with the isolated representation. Here we propose an extension of CoMeta which allows the user to select which metabolites should be considered as interactions of interest, discriminating between input and output metabolites. We illustrate some experiments which show the advantages of this more flexible approach. Our experience suggests that in general a good choice is to take as open metabolites those which are the input and output compounds for the pathway.