Fig. 6

The three conditions for threshold effect. First, an ultrasensitivity module need to be embedded in the gene regulatory network. The system is normally in a stable (homeostatic) state, i.e., the wildtype state, and is robust to small fluctuations. Second, the occurrence of a primary (driver) mutation shifts the system to a state that is ultrasensitive to changes in the concentration/activity of factor X ([X]). If [X] does not fluctuate, then the system would have a fixed [X] and a fixed outcome. Third, fluctuations in [X] would cause the system to produce heterogeneous phenotypic outputs