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Benchmarking gene expression signatures following TAS1553 exposure in combination with either SRA737 or prexasertib.A Volcano plots of IMR-32 (top) and CLB-GA (bottom) of significantly DEGs after treatment with 0.74 nM prexasertib and 0.88 µM TAS1553 for 48 h. Genes indicated by name cover the top 15 DEGs. NS not significant. B Volcano plots of IMR-32 (top) and CLB-GA (bottom) of significantly DEGs after treatment with 0.28 µM SRA737 and 0.51 µM TAS1553 for 48 h. Genes indicated by name cover the top 15 DEGs. NS= not significant. C Bubble plot showing the top gene sets enriched after the indicated combination treatment for 48 h for IMR-32 and CLB-GA. D GSEA of the RNA-seq based transcriptome profiles following combined drug treatment with TAS1553 and prexasertib (left) or TAS1553 and SRA737 (right) in IMR-32 cells showing a significant overlap between genes enriched upon combination treatment of TAS1553 with prexasertib, TAS1553 with SRA737 or 3-AP with prexasertib. E Heatmap showing the NES scores from our different combination treatments compared to publicly available gene sets [4, 5, 43–45]. F Representative immunoblotting data for MYCN in IMR-32 following 48 h treatment with 0.74 nM prexasertib and 0.88 µM TAS1553 or 0.28 µM SRA737 and 0.51 µM TAS1553. The quantification of all replicates (N = 3) is shown in Supplementary Figure S8B, D.
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