Fuzzy Logic Analysis of Kinase Pathway Crosstalk in TNF/EGF/Insulin-Induced Signaling
Figure 5
The experimental data compendium and simulation of the global FL model.
(A) The left heatmap portrays the averaged normalized data from the experimental compendium [20]. Ten stimulation conditions with TNF, EGF, and insulin (top) are shown with the measurements at 0, 5, 15, 30, 60, 90,120, 240, 480, 720, 960, 1200, and 1440 minutes below. Measurement types (western blot or kinase assay) are indicated in Figure 4A and are described in detail in Gaudet et al. [43]. In the middle, the heatmap shows the results of simulation using the global model under normalized treatment conditions, corresponding with the data compendium shown on the right. Identical simulations of an equivalent discrete logic model (DL, built by changing only the degree of fuzziness from the FL model and leaving the rules and MF thresholds unchanged) are shown on the left (see Methods). The cytokine treatment concentrations are marked directly on the heatmap in ng/mL for the data and arbitrary units for the models. See Figure S5 for an alternative depiction of the data and simulation results. The FL and DL models have fitnesses of 44.6 and 96.7, and normalized fitnesses of 0.035 and 0.076, respectively. (B–D) Simulation and data time courses are plotted for three treatment conditions to highlight cases where the FL model fit the data better than the DL model (B), where both models have similar performance (C), and both models fail (D).