Supplementary Figure 3: Metastatic progression master regulators selected for validation. | Nature Genetics

Supplementary Figure 3: Metastatic progression master regulators selected for validation.

From: A precision oncology approach to the pharmacological targeting of mechanistic dependencies in neuroendocrine tumors

Supplementary Figure 3

a, Conservation of the top 25 most activated and top 25 most inactivated master regulators between 66 NET liver metastases. b, Optimal number of clusters based on the regulators of metastatic progression for 66 liver metastases. c, Enrichment for the targets of all significant metastasis master regulators, including transcripts that according to the regulatory model are induced by the master regulator (indicated by red vertical lines) and represented (blue vertical lines). The x axis indicates the genome-wide expression signature (GES) for the patient 0 metastasis (genes are sorted from the most downregulated to the left to the ones most upregulated to the right) and the H-STS cell line GES. Statistical significance is shown as Bonferroni’s corrected P value (two-tailed aREA test). d, Effect of each individual shRNA hairpin (indicated with different colors) on the expression level of the targeted gene as compared to the effect of non-targeting shRNA control. Three replicates were performed per hairpin, and at least two hairpins were assayed per gene. P values were estimated by one-tailed ANOVA. e,f, Effect of master regulator silencing on the viability of KRJ-1 (e) and NCI-H716 (f). Three replicates were performed per hairpin. At least two hairpins were used per gene (indicated in different colors). P values were estimated by one-tailed ANOVA.