Systematic, network-based characterization of therapeutic target inhibitors
Fig 2
CMAP and LINCS dataset analysis.
(A—B) Analysis for drugs targeting 75 TRs using either DTPA or DTGE for CMAP MCF7 datasets. For each TR with known inhibitors in the MCF7 dataset, we performed gene set enrichment analysis to test whether its DTPA or DTGE for its known inhibitors are significantly more inactivated or repressed compared to all other compound’s profiles (A) or to all other proteins (B) and obtained p-values from each test. Then we plotted the distributions of the–log10 p-values for DTPA (x-axis) versus DTGE (y-axis). Each triangle represents a TR. A vertical and a horizontal line were drawn at p-value equals 0.05 for DTPA and DTGE, respectively, which divide the plot into four parts: green, blue, red, and grey. (C) Enrichment analysis of the drug samples similar to TR silencing profiles on the vector of all drug samples in the same cell line sorted based on their inferred TR activity from LINCS data set. Each bar represents a cell line. Green color shows the number of TRs with significant enrichment (NES > 1.96; p < 0.05) which indicates the correlation between OncoLead CMoA inference and shRNA mediated TR silencing. Grey color shows the number of TRs without significant enrichment (NES< 1.96; p > 0.05). (D) OncoLead-inferred ESR1 activity changes (blue) and the differential ESR1 expression (red) upon letrozole treatment in vivo. Signatures are obtained by comparing different time points in responsive and non-responsive patients. The values shown in the figures are Z-scores based on p-value. The black dotted line represents Z-score = 1.96 and p-value = 0.05.