Fig. 6: Interferon signalling and methionine metabolism are enriched in ranolazine-treated BRAFi-resistant melanoma cells.
a, UMAP visualization of 6,457 VR and VR_RANO cells coloured by Seurat clusters. b, Hypergeometric test for enrichment analysis using cluster gene markers against the MSigDB hallmark gene-set collection. Only VR_RANO clusters enriched at significance level of Padj < 0.05 are indicated. The percentage of VR_RANO cells distributed in the respective VR_RANO main clusters is indicated for each hallmark. c,d Quantification of cellular ROS levels in VR cells in the presence or absence of RANO and of glucose uptake in VR and VR_RANO cells. Data are presented as the mean ± s.e.m. based on n = 5 (c) and n = 3 (d) biological replicates analysed by two-tailed unpaired t-test. 1. e,f, Hallmarks (e) interferon gamma response and interferon alpha response (f) signature scores in VR_RANO or VR cells represented by violin plot (top) and UMAP (bottom). g, Hypergeometric test for enrichment analysis using cluster gene markers against the KEGG pathway and GOBP gene-set collections. Only VR_RANO clusters enriched at significance level of P < 0.05 are indicated. The percentage of VR_RANO cells distributed in the respective VR_RANO main clusters is indicated for each term. h, UMAP visualization coloured by MTAP, MAT2A and SMS expression.
