Fig. 5
From: Drug and disease signature integration identifies synergistic combinations in glioblastoma
Synergistic response of cell proliferation inhibition and apoptosis after treatment with JQ1 and/or GSK-1070916. a Ranking of the 285 LINCS compounds based on their orthogonality to the GBM-JQ1 consensus signature. Compounds with a high x-axis value have a signature concordant to JQ1 and compounds with a high y-axis value have a signature discordant to the disease. b, c Synergy was assessed for a total of 5 cell lines and the Bliss synergy scores (b) and the Loewe combination indices (c) were plotted against the cell line-specific discordance from GSK-1070916. A strong correlation was seen between increased discordance and increased synergy (higher Bliss score, lower Loewe CI). d Reduced cell proliferation measured by ATP levels using CellTiter-Glo® are normalized to positive control (Velcade) and negative control (DMSO). From left to right, the Bliss score surface and an isobologram plot of the Loewe combination index for the combination of JQ1 with GSK-1070916. Synergy analyses for additional cell lines can be found in Supplementary Figure 4. e Apoptosis measured by Caspase3/7 levels using Caspase-Glo® and normalized to positive control (Velcade) and negative control (DMSO). f Synergistic response of the Bliss score surface observed using JQ1 with GSK-1070916 as measured by CellTiter-Glo®. g Sub-synergistic response of the Bliss score surface observed using JQ1 with SR1277 as measured by CellTiter-Glo®. Source data can be found in the Source Data file, Supplementary Data 6, under tab Fig. 5
