Topological view of the transcriptional regulatory response network (TRRN) of S. mutans biofilms upon carolacton treatment. The TRRN was inferred by overlaying the regulator-target gene binding site map onto the co-expression network. It consisted of 27 co-regulated gene groups or subnetworks each under the control of a transcription factor and comprised 329 regulatory interactions involving 307 genes. Some of the co-regulated gene groups overlap with each other as a result of genes modulated by more than one transcription factor. The 27 regulators with outgoing connections (marked with red circles) along with 10 other regulators only with incoming connections (marked with black circles) found to be among target genes within the sub-networks are indicated as well as non-regulator target genes (indicated by green circles). If the upstream regulatory regions of the target genes or their corresponding operons harbored multiple putative binding sites of its predicted regulator(s), then they are indicated by orange circles). In addition, the regulators with outgoing connections are also marked with their gene names above their respective nodes. Blue arrows indicate a positive (activation) relationship whereas red arrows stand for a negative (repression) effect. Connections always flow from top to bottom. Spatial positions of transcription factor nodes are manipulated so as to pictorially depict the possible hierarchies. The carolacton context TRRN shown herein is observed to be organized as a double layered hierarchy. The network was visualized using Cytoscape.