Because of the variable level of network details, we call this type of models meso-scale networks. Recently it has been shown, that the topology of such meso-scale networks can be reconstructed from data without fitting of models, even if BMS 453 almost no restriction is assumed for the functional form of the nodes. The drawback is that the method so far requires a feed-forward structure which can be decomposed into tree structures, so no feedback loops can be identified. Hence the method is mostly restricted on network reconstruction on a rough level of details. Although this approach does not directly specify the role of specific biological mechanisms in drug response, it allows the assessment of the number of pathways and their interaction providing hypothesis for detailed mechanistic follow-up research. It thereby provides a valuable approach which is complementary to the established methods providing an unbiased assessment of mechanisms and their interaction on a proteome-wide scale in a first level analysis. Chronic myeloid leukemia represents an excellent model disease for development of cancer-specific TKIs. Currently, three different TKIs, Imatinib, Nilotinib and Dasatinib, are approved for first and second line treatment and novel drugs such as dual BCR-ABL/src inhibitor Bosutinib, dual aurora/BCR-ABL inhibitor Danusertib and multi targeted TKI Ponatinib are being evaluated in clinical trials. From clinical use and experimental evidence it is known that the efficacy and side-effect profile of individual TKIs depends on targeted MoA as well as on indirect responses based on the unspecific inhibition of various kinases. In order to identify co-regulation between induction of apoptosis and overall protein expression, we analyzed the correlation between induced apoptosis rate and the mean component of protein expression discussed above. The results, depicted in Figure 7C, show a surprisingly good correlation between the sum of the induced protein expressions and induced apoptosis. This correlation holds for almost all TKIs and all cell lines, only two outliers have been found. Detailed analysis of the results depicted in Figure 7C shows that omitting DASA from the analysis results in a reduction of the mean deviation from the linear relationship between the protein induction and apoptosis induction by 18%. We find that the mean protein induction of DASA in the three cell lines is significantly higher than expected by the induction of apoptosis. These results suggest that, in contrast to the other TKI��s, DASA can significantly induce protein expression aside from induction of apoptosis. However, as indicated in Figure 7C, the impact of the drugs on protein expression in relation to induction of apoptosis depends strongly on the type of ALX 5407 hydrochloride mutations in the cell lines.