Fig. 1
From: Defining subpopulations of differential drug response to reveal novel target populations
Segmentation of a population based on pharmacological patterns of response discovers subpopulations with differential response. a Dose response curves of two or more drugs are measured across a population of just over 1000 cancer cell lines. b The population is segmented into distinct and homogeneous subpopulations based on their response to multiple drugs. When comparing two drugs, subpopulations can be categorised based on their mean log(IC50s): sensitive to both drugs (orange), sensitive to drug A but not drug B (green), sensitive to drug B but not drug A (blue), and resistant to both drugs (grey). c Segmentation results for a BRAF inhibitor (SB590885) and a MEK inhibitor (CI-1040). Tree nodes contain the number of cell lines and are coloured based upon their category of response. Significance testing of 735 cancer functional events reveals subpopulations enriched for BRAF and KRAS mutations. d Scatter plot showing derived subpopulations based on their pharmacological responses for afatinib and selumetinib. Dashed lines indicate 20th percentile of log(IC50) values for each drug. PIK3CA, EGFR, ERBB2, KRAS, NRAS, BRAF, APC, TCF4, and RB1 mutations were found enriched in the associated subpopulations. e OncoPrint visualising the percentage of mutations of selected genes in cell line panel treated with either afatinib (EGFR inhibitor) or selumetinib (MEK inhibitor). The waterfall plots comparing the response of the cell lines to afatinib and to selumetinib. f Boxplot of difference in log(IC50) values between afatinib and selumetinib response for wild-type cell lines, all cell lines with PI3KCA mutation, and cell lines in derived subpopulations with enriched PI3KCA mutation. g Same as panel f, but for BRAF mutations
