Mathematical Model of a Telomerase Transcriptional Regulatory Network Developed by Cell-Based Screening: Analysis of Inhibitor Effects and Telomerase Expression Mechanisms
Figure 7
Topological control of TERT on-state multiplicity in the model.
(A), influence of activation module dominance on TERT on-state multiplicity. Topology of the model was altered by a series of 600 random attacks deleting activation and repression module interactions with increasing probability. Direct interactions with TERT were left unaltered in all attacks. The remaining sub-networks were extracted from each model variant as described in materials and methods and the number of edges in each were counted to determine the edge ratio AM/RM. The statespace of each model was calculated and the number of stable on states present for the TERT node was quantified and plotted against the calculated AM/RM edge ratio for each variant network. Significance of edge ratio population differences was tested in Matlab by Wilcoxon rank-sum test (**: p<0.01). (B), influence of AM dominance in random networks. A series of 300 (15 node) networks was generated with semi-random edge seeding and increasing edge density. All networks were constrained to have one regulated node which was connected downstream of all others. The number of activators and repressors of the node was allowed to vary randomly. Statespace and AM/RM edge ratios were calculated for each network and compared as in (A), calculating number of stable on-states for the fully connected node. Significance of edge ratio population differences was tested in Matlab by Wilcoxon rank-sum test (**: p<0.01).