Mathematical Model of a Telomerase Transcriptional Regulatory Network Developed by Cell-Based Screening: Analysis of Inhibitor Effects and Telomerase Expression Mechanisms
Figure 2
Topology, steady states, and statespace structure of the TERT transcriptional neighbourhood model.
(A), topology and steady states of the basal TERT model. Transfection screening data were used to assign activating or repressive network interactions according to the direction of regulation of each promoter and using the cut-offs of minimum fold-change 1.5 up- or down-regulation of promoter activity and p-value (ANOVA)<0.01. Topology of the final model was visualised in Cytoscape [105]. Arrows indicate activation, T-shape indicates repression. Left and right panels show steady states 1 and 2, respectively. Red colour indicates the node is on, green colour indicates the node is off in each steady state. (B), core statespace structure of the model. Statespace was calculated by brute force and visualised in Pajek [103]. Basins of attraction were extracted as weak components of the statespace. To visualise the core structure, all nodes with in-degree ≥1 were extracted as new networks from each weak component and visualised with transient states in blue and attractor states in yellow. Left panel corresponds to state 1, right panel corresponds to state 2.