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Fig. 6 | Genome Biology

Fig. 6

From: MICMIC: identification of DNA methylation of distal regulatory regions with causal effects on tumorigenesis

Fig. 6

Tumor-subtype core regulatory circuitry and pan-cancer global topology of TF network regulated by DNA methylation of distal DREs. a The interconnected auto- and cross-regulation loops within the CRC TFs. The links between TFs were derived from distal DRE-target pairs in which the DRE harbors binding sites for the CRC TFs. The TFs are colored by the tumor subtypes in which they are highly expressed. Effects of the CRC on tumorigenesis are analyzed by the cancer pathway enrichment of the TFs’ targets (hypergeometric p value < 0.05), representing in the right side of the CRC. b Top: Heatmap of the expression Z-score of CRC TFs in the tumor subtypes. Bottom: Joint consensus clustering by the expression of CRC TFs and methylation of binding DREs shows a great similarity between the CRC subtypes and PAM50 subtypes in breast cancer. See results of other cancers in Additional file 1: Figures S17–S19. c Signaling pathways in breast cancer regulated by CRC TFs whose targets were identified by the distal DRE-target pairs in which the DRE harbored the TF binding sites. Each color of a gene node indicates a different cancer pathway. Edges represent regulatory relationships. d Convergence of network topology across cancer types (see “Methods”). For each cancer type, their TF networks were decomposed and categorized into 13 different types of basic three-node network motifs, indicated by the topology structures above the graph. The X-axis shows the numerical identification number associated with each motif. The relative enrichment (Z > 2) or depletion (Z < − 2) of each of the 13 basic network motifs for each cancer type was calculated as a Z-score (Y-axis)

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