Interrogating the topological robustness of gene regulatory circuits by randomization
RACIPE was tested on three circuits–a simple toggle-switch (TS, top left) which consists of genes A and B that mutually inhibit each other (solid lines and bars), a toggle-switch with one-sided self-activation (TS1SA) which has an additional self-activation link on gene A, and a toggle-switch with two-sided self-activation (TS2SA) which has additional self-activation links on both genes. (A) Probability distributions of the number of stable steady states for each circuit. (B) Probability density maps of the gene expression data from all the RACIPE models. Each point represents a stable steady state from a model. For any RACIPE model with multiple stable steady states, all of them are shown in the plot. (C) Average linkage hierarchical clustering analysis of the gene expression data from all the RACIPE models using the Euclidean distance. Each column corresponds to a gene, while each row corresponds to a stable steady state from a model. The analysis shows that the gene expression data could be clustered into distinct groups, each of which is associated with a gene state, as highlighted by different colors on the right of the heatmaps.