Fig. 5. KRAS effector pathway and information flow (IF) analysis of the EGFRNet^mtKRAS-Hi and EGFRNet^mtKRAS-Lo networks.

a Dependence of KRAS-effector complex concentrations of effectors binding with high (RAF1, blue) or low affinity (RALGDS, red) on the abundance of mtKRAS. Broken gray lines indicate KRAS concentrations in mtKRAS^Lo and mtKRAS^Hi cells. b Plot showing nodes in the top 5th percentile in terms of their IFS and predicted to receive more flow in EGFRNet^mtKRAS-Hi (red) or EGFRNet^mtKRAS-Lo (blue). c Transcription factors (TFs) with at least 20% higher information flow in EGFRNet^mtKRAS-Hi (red) and EGFRNet^mtKRAS-Lo (blue). Gene expression of d FOXO1, e MYC, f FOS, and g STAT1 as determined by RNAseq analysis of TGFα stimulated cells. ***EdgeR FDR < 0.001; ****EdgeR FDR < 0.0001. The top five enriched transcription factor binding (TFBS) site motifs in the promoters of genes upregulated in h mtKRAS^Hi and i mtKRAS^Lo cells. j Reporter gene assays of the activity of STAT1/2 and STAT3. Error bars represent standard deviation, and P values in K were determined by a two-tailed Student’s t-test. *P < 0.05; **P < 0.01. The data represent three independent experiments. Source data are provided as a Source Data file. Mathematica code for 5A is provided in Supplementary Software 1.