Fig. 4

Functional genomics scrutiny of associations between curated TF hits. a Curated AI peaks that contained key TFs associated with each other. Oval and rectangle nodes represent loss and gain peaks, respectively. An edge is drawn between nodes if genome wide corrected association p-value < 0.001 (logistic regression). Width of edge is proportional to effect size. All edges represent positive association. b Regulatory circuitry of the transcription factor targets of AI. siRNA silencing followed by RNA-seq were used to detect positive and negative regulatory relations between TFs with FDR < 0.05 (Wald test). Red edges detected in GP5d cell line, orange in LoVo, purple in both. Asterisks depict concordant expression relation between the pair of TFs (FDR < 0.05) in the regression analysis of RNA-seq data from 259 colorectal tumors as compared to siRNA experiments (details in Supplementary Methods). Thick lines show potentially direct regulation based on the presence of the corresponding ChIP-nexus/exo peaks. Note that the cell lines tested displayed different regulatory states of the network, but the MYC gene was essential in all, based on the CRISPR/Cas9 screen, suggesting that individual tumors utilize different upstream mechanisms to drive cell growth through MYC³⁹