Fig. 4: Uveal melanoma-specific essential genes are involved in GPCR signaling and phosphoinositide signaling pathways.
a, Uveal melanoma-specific gene hits (log2(FC) > 1.80 and Padj < 0.01; two-tailed Mann–Whitney U test with Benjamini–Hochberg correction). Significantly differential essential genes for uveal melanoma cell lines were computed by comparing gene essentiality scores from our uveal melanoma screens to genome-wide sgRNA CRISPR screens from DepMap 22Q2 (Methods; Supplementary Table 11). Blue dots denote the top uveal-specific essential genes; green dots are genes less essential in uveal cell lines versus pan-cancer. b, Pathway enrichment analysis of the 76 uveal melanoma-specific genes using GO molecular function pathways. c, Dependency rank of top ten genes in uveal melanoma compared with pan-cancer cell lines. As above, pan-cancer data obtained from DepMap52 22Q2 release. The analysis compared the 10 uveal lines to 982 pan-cancer cell lines. The box shows the IQR, the line marks the median, whiskers extend to data within 1.5× from Q1 and Q3, and points beyond are outliers. d, Validation of genome-wide sgRNA CRISPR screen hits with a competitive coculture assay (Methods). Cells were transduced with a lentivirus expressing an sgRNA and a BFP marker. BFP expression was measured by flow cytometry at baseline and on days 14 and 28. The proportion of surviving sgRNA-transduced cells compared with nontransduced cells is normalized to day 4. Two sgRNAs were tested against each gene, and an STG sgRNA was used as a control. Data represent three independent experiments performed in triplicate, with the mean and s.d. shown. Significance was calculated using a two-way ANOVA with Tukey’s multiple test correction. ****P < 0.0001, **P < 0.01, *P < 0.05 (exact P values are provided in the source data).
