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Utility of constraints reflecting system stability on analyses for biological models

Fig 6

Utility of TEAPS in the analyses of arachidonic acid pathway model.

(A) The model containing arachidonic acid pathways in polymorphonuclear cells (PMN), endothelial cells (EC), and platelets (PLT) was reconstructed according to the previously reported model structure. The Michaelis-Menten constants were set to the same values if there were same reactions in different cells. The reactions which only appears in each cell type are colored in cyan (PMN), pink (EC), and brown (PLT). The reactions with black arrows are shared with at least two cell types. For modifications on reactions, lines ending with a circle indicate promoting effect on a reaction whereas lines ending with a bar indicate inhibitory effect. Modificative effects by metabolite but not enzymes are described as dashed lines. (B) The estimated basin stability was increased by individual optimization process (gL-BFGS) when TEAPS were applied to the arachidonic acid pathway model. (C) The parameter sets obtained for the arachidonic acid pathway model were subjected to the principal component analysis. To figure out the entire shape of the parameter distribution, the number of components was set to the number of parameters in the model. (D) The reactions with tight and robust regulation were searched. Each arrow corresponds to each parameter on every reaction. The reactions related with parameters that appeared as high contribution to PCA axes in which the parameter distributions are narrow are colored in red, while those to each of the PCA axes in which the parameter distributions are broad are colored in blue.

Fig 6

doi: https://doi.org/10.1371/journal.pcbi.1010441.g006