Fig. 3: Genome-wide single gRNA CRISPR screening identifies CDS2 as an essential gene in uveal melanoma.

a, Plot showing the distribution of genes in each cell line following genome-wide CRISPR screening. Dotted line denotes a MAGeCK MLE beta of +0.5 or −0.5. For each cell line, ‘_NE’ indicates scores filtered for common essential genes (DepMap 24Q2) and core essential genes (CEGv2), with genes that are significant in ≥6 lines shown as triangles (MLE beta +0.5 or −0.5 and an FDR < 0.01). The genes significant in most lines are labeled even if they are not significant in a specific line. b, Genes from two-gene paralog families that were a hit displayed with their beta values. The paralogous genes for these screen hits are shown in parentheses. Each dot represents a cell line. c, Top paralog gene pairs identified from single gRNA CRISPR data. The data shown is the relative gene expression levels of these pairs derived from our ten screened uveal cell lines (top) and the 80 tumors in the TCGA uveal melanoma dataset³⁸ (bottom). These data illustrate that in patient samples, the genes CDS2, RIC8A and SPTSSA are robustly expressed at levels much higher than their paralog gene partner. Also shown is an analogous expression pattern in our uveal melanoma models (Supplementary Table 3). The box shows the IQR; the line marks the median; whiskers extend to data within 1.5× IQR from Q1 and Q3. d, NNMD values for the whole-genome screens for each of the ten cell lines analyzed in comparison to Project Score screens⁴⁷.