Connections between gene signatures induced by small molecule drugs in MCF-7 breast cancer cells and a query signature.

The query signature consisted of the differentially expressed genes in ER-negative breast tumors comparing African-American with European-American patients. Shown is a heatmap with the color-coded connectivity score (−1 to +1) for individual sets of experiments exposing MCF-7 cells to sirolimus, resveratrol, or two phenothiazines, fluphenazine and chlorpromazine. The heatmap shows that negative correlations between drug-induced signatures and the query signature were found for multiple experiments with MCF-7 cells. Green: negative connectivity indicating an antagonist effect of the drug on the query signature. Black: no connectivity. Red: positive connectivity indicating an agonist effect. Different cutoffs were used for inclusion of differentially expressed genes in the query signature: (1) P≤0.01, (2) P≤0.01 and fold change at least 1.5-fold, (3) P≤0.05 and fold change at least 1.5-fold. The negative correlations between signatures induced by sirolimus, resveratrol, or chlorpromazine, and the query signature were statistically significant at P_permutation<0.05, respectively, in the combined analysis with n = 8 for sirolimus, n = 4 for resveratrol, and n = 4 for chlorpromazine.