Fig. 3

The validation of the proposed network through the demonstration of cancer reversion phenomena. a Data-based weight fitting results from the scoring system. We have ranked the order of malignancy for each mutation profile based on the experimental data (first column on the left). The three cell state scores for each aspect were obtained from the attractor landscape simulations after projecting each mutation profile to the network (middle three columns). To fit the cell state score ranks with the experimental data, each cancer proximity score is weighted and summed. As a result, the colorectal cancer network with the same mutational profile from the experimental data was sorted in similar ranks with the experimental results (last column on the right). b Various qualitative input-output relationships obtained from the proposed network model. The activation ratio of eight marker nodes has been measured along with the increase of the three input nodes independently. As a result, the input-output response curves are well in accord with the previous experimental data. c Clustering the CMSs in the space of cancer proximity scores according to the mutation profile of each subtype. 12 normal colon cell networks with various expression fold changes (black dots) are well clustered in the upper region of the three-dimensional space in our scoring system. After the projection of CMS mutation profiles in colored dots, the network models were well clustered according to the CMS in the three-dimensional space of cancer proximity scores. Moreover, the CMS4 network models (red dots) were predicted to be in the most malignant state, which agrees with the previous studies [29]. d Cancer reversion phenomena mediated by APC restoration. The reversion phenomenon was observed in terms of the normal-like score recovery to that of a normal colon cell after the APC restoration of colon cancer cell. The increase of normal-like score due to the APC restoration (difference of normal-likes scores in last red and blue column on the right) is much higher than those of APC hyper-activation (difference of normal-likes scores in last red and gray column on the right), KRAS restoration (difference of normal-likes scores in third and last red column from the left) and p53 restoration (difference of normal-likes scores in second and last red column from the left)