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. 2018 Mar 7;37(21):2850–2862. doi: 10.1038/s41388-018-0135-1

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 3 — Comparing the transcriptional output from MYCN suppression with BET and CDK inhibition in order to identify essential gene targets. Characterizing the transcriptional changes induced after 6 h treatments. a–d GSEA results for the top MYCN target gene-related gene set (NMYC_01) downregulated in GTML-DOX-6h as compared to GTML–DMSO-6h (a); the GSEAs for the same gene set are shown comparing GTML-DMSO-6h with GTML-JQ1-6h (b), GTML-Milciclib-6h (c), and GTML-JQ1+Milciclib-6h (d). Enrichments were considered significant if FDR < 0.05. e, f Venn diagrams displaying the number of genes significantly upregulated (e) or downregulated (f) in each treatment as compared to DMSO and the overlap of regulated genes between treatments. g, h Bar plot depicting the number of genes significantly upregulated in two TP53/apoptosis gene sets (g) or downregulated in three MYC/MYCN gene sets (h) in GTML-DOX-6h as compared to GTML-DMSO-6h and shared with similarly regulated genes in GTML-JQ1-6h, GTML-Milciclib-6h, or GTML-JQ1+Milciclib-6h; gene sets were identified in a and Supplementary Figure 3b. Genes were considered significantly regulated if at least one condition was expressed (log10(FPKM + 1) > 0.50), the FDR adjusted p-value q < 0.05, and if log2(FC) > log2(1.5) (upregulated) or log2(FC) < −log2(1.5) (downregulated)