Extended Data Fig. 4: Deconstructing cytokine induced cis-regulatory networks in β cells.

a, Gene Regulatory Network (GRN) derived from IREs and their putative target genes. Squares represent the IREs inferred TF binding sites (motifs logos and TF matches are shown on the right side) and the ellipses represent their putative target genes (see Methods). The size of the squares reflects the number of connections (edge count) while the gene node size reflects the log₂ fold change of RNA expression after cytokine exposure. The resulting GRN is an interconnected scale-free network composed of 648 nodes and 3,589 edges. Genes regulated exclusively by primed IREs are represented in blue while green depicts opening IREs regulated genes. Red denotes genes regulated by both types of IREs. In each of these three groups the representation of the hierarchy is based on the principle of network centrality where authoritative nodes are located more proximal to the core. b, Comparison between the degree distribution of the observed GRN (black triangles) and a random generated network (blue squares) having the same number of nodes and edges. The bell-shaped degree distribution of random graph denotes a statistically homogeneity in the degree of small and large nodes. In contrast, the observed network showed a high frequency of small degree nodes and a low frequency of highly connected nodes as is typical of a scale-free network. c, Bar plot of gene ontology biological process enrichment analysis. Gene-ontology analysis was performed using all target genes in the GRN. Functional enrichment analysis was performed by Metascape (http://metascape.org). Only terms with P < 0.001 and with at least 3 enriched genes were considered as significant. Color is proportional to their P values.