fig3

Figure 3. Graphical summary of the systems workflow used to dissect the mechanism of action for the mTOR inhibitor (mTORi) and HDAC inhibitor (HDACi) drug combination^[19]. Initial ANOVA analysis from our gene expression profiling data started with 1647 differentially expressed genes. Weighted gene co-expression network analyses determined that there were 901 genes in the entire drug response network. Of these 901 genes, 126 genes could be assigned to the drug combination network. These genes were then evaluated for enrichment in myeloma vs. normal samples from the same patient (GEO databases) and by multivariate prediction modeling to assess their association with patient survival. 37 disease-specific genes were chosen for further analyses. When the data for the 37 genes (PatentUS2014357660-A1) was evaluated by IPA, 6 master regulators, including MYC, Rb, and Cdkn2a were identified. ANOVA: analysis of variance; GEO: gene expression omnibus; IPA: ingenuity pathway analysis