Figure 5

Properties of the EGF/TNFα model analysed with GINsim. A) The Hierarchical Transition Graph (HTG) representing the dynamics of the reduced model (i.e., [pseudo-] outputs removed), under the asynchronous scheme, starting from the null initial state and the EGF = 1 & TNFα = 1 condition. The HTG shows the organisation of the dynamics with a chain of 13 irreversible sets (grey nodes, each encompassing 36 states) connected, at each stage, to a chain of 12 transient cycles (light blue nodes, each encompassing six states) and a unique cyclic attractor (pink node, also encompassing six states). B) By defining a lower priority for the update of IKK, all transition states towards transient cycles (in light blue in panel A) are prevented: the system reaches the cyclic attractor without visiting the same state twice. On the right of the panel B, the corresponding State Transition Graph (STG) starting from the initial state (contained in the HTG state set in green) and leading to the cyclic attractor (pink nodes). This STG is shown to illustrate the complexity of the transient dynamics and is not meant to be readable. C) The HTG showing that, under the asynchronous scheme, different attractors are reachable. Here the two cyclic attractors differ by the value of ph (arrows in bold embody transitions increasing the value of ph). D) Stable states for the wild-type, IKK knock-out and ectopic expression of ERK, respectively.