Fig. 2

Demonstration and test of CaiNet using a repressive gene cascade. a Regulatory logic of a repressive gene cascade of four genes (left panel) and sketch of the corresponding GRN including transcription repressors and gene elements (right panel). The input species (constant level of 100 molecules) and each gene product repress the subsequent gene element in the GRN. b, c Simulation scenario 1 of CaiNet with deterministic treatment of gene on/off switching and birth/death events of gene products. b Sketches of the probability of activated expression of a gene (upper panel) and the corresponding gene product level (lower panel) of scenario 1. The activation of a gene is constant within one synchronization time step. After each time-step, all gene product levels are synchronized and the activation probabilities of all gene elements are updated. c Comparison of CaiNet simulations of the repressive gene cascade according to scenario 1 performed with different synchronization time steps (red, yellow and purple lines) with the numerical solution of an ODE solver (dashed blue line). d, e Simulation scenario 2 of CaiNet with stochastic treatment of gene on/off switching and deterministic treatment of birth/death events of gene products. d Sketches of the production state of a gene (upper panel, either on or off)) and the corresponding gene product level (lower panel) of scenario 2. e Left panel: comparison of a CaiNet simulation of the repressive gene cascade according to scenario 2 (red line) with the numerical solution of an ODE solver (blue line). f–j Simulation scenario 3 of CaiNet with stochastic treatment of gene on/off switching and birth/death events of gene products. f Sketches of the production state of a gene (upper panel, either on or off)) and the corresponding gene product level (lower panel) of scenario 3. g Left panel: comparison of a CaiNet simulation of the repressive gene cascade according to scenario 2 (blue line) and scenario 3 (red line) with a Gillespie simulation (yellow line). h, i As in f, g, but with faster gene on/off switching rates. j As in i, but with a constant input level of 1 molecule. Middle and right panels of c, e, g, i, j: histograms and autocorrelation curves of respective gene product levels. In panels (c, e, g, i, j) the expression level of the last transcription factor in the cascade is shown