Using Transcription Modules to Identify Expression Clusters Perturbed in Williams-Beuren Syndrome
Only genes that appear at least ten times in the dysregulated modules are considered. (A) Most frequent module genes that have at least one connection in the STRING database. Edges with evidence score higher than 0.3 are shown; their colors indicate different kinds of interaction evidence (key bottom right). (B) Most frequent module genes form a network that is denser than a random subnetwork of the same size in STRING. We generated 10,000 random subnetworks and calculated the sum of the evidence for all edges. Only five out of all random subnetworks show a higher total evidence value than the most frequent module genes indicated by a red asterisk (sum of total evidence = 69,033). (C) Distribution of the number of connections (node degree) per protein in the complete STRING network (black, filled circles), and the subnetwork of most frequent module genes (red, open squares). The subnetwork has significantly less low-degree nodes and more high-degree nodes (Wilcoxon-test P = 1.612×10−5). (D) Distribution of PageRank centrality scores in the complete STRING network and the subnetwork of most frequent module genes. The subnetwork has fewer non-central nodes and more central nodes (Wilcoxon-test P = 2.628×10−5). (E) We fitted hierarchical models  to the subnetwork of the most frequent module genes, and also to 1,000 randomized networks. The network of frequent module genes (red asterisk) shows no hierarchical structure compared to the randomized networks.