Subset of the results of a CellNOptR analysis on two time-point data from human hepatocellular carcinoma cells. The data consists of phospho-proteomic measurements of 16 proteins in response to multiple inducers of inflammation, innate immunity and proliferation, applied in combination with selected small molecule inhibitors . This figure shows a simplified version of a small subset of the trained model (blue nodes=measured, green=stimulated, red=inhibited; green edges=picked at τ1, blue edges=picked at τ2), along with the data associated with the creb node (right, solid black line), overlaid with the simulation results (dashed blue line) for a selected set of conditions. The background color indicates the goodness of fit of simulation results to data. We can see that the model captures the behavior of creb accurately: creb increases at τ1 if either MP2K2/MP2K1 or p38 are activated (in this case, because both are downstream of IL1A, they are both activated in the absence of inhibitors and presence of IL1A). This activation is maintained if both MP2K2/MP2K1 and p38 are activated, and is lost at τ2 (180 minutes) if only one of them is activated (i.e. in this case if either is inhibited). This behavior is captured in the model by selecting an OR gate from MP2K2/MP2K1 and p38 to creb at τ1, and an AND gate at time τ2.
Terfve et al. BMC Systems Biology 2012 6:133 doi:10.1186/1752-0509-6-133