Figure 4. “Hidden” regulatory proteins in signaling pathways.

(A) FGFR3 and p90RSK2 in this simple network are not affected on the gene expression level, therefore remaining “hidden” from a microarray assay. We identify sets of remote targets associated with each of the signaling molecules and assess their enrichment with differentially expressed genes. Remote targets of FGFR3 and p90RSK2 are proteins within the blue box. They could be many steps downstream of signaling proteins. Topological significance is assigned to regulatory nodes based on the enrichment of associated sets of target genes. Red boxes indicate topologically significant nodes in this network. (B) Topological scoring of regulatory nodes in complex networks with competitive regulation. (See text for details).