After incorporating the ITH information into the analysis, PATOPAI now shows that the pathway mutations in colon cancer follow a temporal order of WNT–MAPK–apoptosis–PI3K–p53–TGF-beta signaling pathways (Figure 1d), which agrees better with the ‘classic’ colorectal cancer formation model [1] since it puts p53 after the PI3K signaling pathway. Here, TP53 is linked to colonic neoplasm.