Fig. 3: Validations of gene expression-based combinatorial drug screens.
a TSNE plots of normalized gene expression data. Samples are color-coded based on Autosampler drug (top left panel), Braille valves drug (top right panel), ordered combination (bottom left panel), and unordered combination (bottom right panel). Color code is labeled for autosampler and Braille valves drugs (top panels). b Silhouette scores of sample clustering based on autosampler/Braille valves drugs and ordered / unordered combinations. Silhouettes scores are compared to random distributions (color code) created by permuting sample labels. c Pathway activity heatmap of samples. PROGENy pathway activities were calculated for each sample (z-scores of pathway activities, color code), and the pathway activity matrix was hierarchically clustered. Drugs of combinations are color-coded (light-green: autosampler drug, blue: braille valves drug, cyan: Same drug from autosampler and Braille valves). d Drug-induced pathway activity changes. A linear model (pathway_activity ~YM155 + Imatinib + Trametinib) was fitted for each pathway, and the linear model coefficients (color code) for each drug is plotted as a heatmap. e Drug-induced MAPK activity changes. MAPK activity (y-axis) grouped based on autosampler drug (x-axis) and Braille valves drug (color code), n = 3 biological independent experiments for all samples, except for YM155_Imatinib and DMSO_Imatinib n = 2. The boxplots show the median and first and third quartiles as a box, and the whiskers indicate the most extreme data points within 1.5 lengths of the box. f Correlation of MAPK pathway activities between two 4 × 4 screens, performed with swapped barcode assignments (r = 0.637, p = 0.01, and R2 = 0.406), the shaded area shows a 95% confidence interval of the regression estimate. Source data are provided as a Source Data file.
