Figure 2

Differential gene expression response upon treatment with imatinib or omacetaxine. (A-B) Volcano plots depicting the extent (x-axis) and significance (y-axis) of differential gene expression for each probe set (n = 48,803) after treatment with either imatinib (A) or omacetaxine (B). (C) Results of k-means clustering of the statistically significant probes based on their differential gene expression in response to imatinib (x-axis) or omacetaxine (y-axis) treatment. The color codes for each cluster are indicated in the index, clusters have been referenced consistently throughout the manuscript. The lack of data towards the center of the scatter plot is due to probes that were not significant (in response to either imatinib or omacetaxine treatment), which are not shown in this figure. (D) Point estimates and 95% confidence ellipses for the association of differential gene expression with sensitivity of drug response (SDR). Plotted in this chart are the regression coefficients from the polygenic models (equation (2)) for the set of probes belonging to the color-coded clusters identified in panel C. (E) Heritability of differential gene expression. The data are shown separately for probe sets belonging to each cluster identified in panel C. Pie charts at the top demonstrate the proportion of probe sets within the corresponding cluster that showed a heritability value exceeding zero for differential gene expression in response to imatinib as well as omacetaxine. The bar charts show the mean heritability of imatinib (blue) and omacetaxine (red) response for genes within each cluster. For reference, color-coded background is shown on the chart corresponding to the clusters. Within each cluster, the difference in the mean heritability for imatinib and omacetaxine response was assessed using a paired Student’s t test, the result of which is shown as the p-value at the top of the bars. ih2r, heritability of differential gene expression in response to imatinib; oh2r, heritability of differential gene expression in response to omacetaxine.