Fig. 2: Systematic genomic and functional characterization of RPE1 clones.
From: Human aneuploid cells depend on the RAF/MEK/ERK pathway for overcoming increased DNA damage
a Copy number alterations (CNAs) across the RPE1 clones. Highly-aneuploid clones, SS51 and SS111, exhibited the highest number of CNAs. b Preranked GSEA of the differential gene expression patterns (RNA-sequencing) between the pseudo-diploid SS48 clone (control) and the highly-aneuploid SS51 and SS111 clones. Plot presents enrichments for the Hallmark, KEGG, Biocarta and Reactome gene sets. Significance threshold set at q-value = 0.25. Enriched pathways are color-coded. c GSEA of the differential protein expression patterns (proteomics) between the pseudo-diploid clones SS48 and SS31 (controls) and highly-aneuploid SS51 and SS111 clones. Plot presents enrichments for Hallmark, KEGG, Biocarta and Reactome gene sets. Significance threshold set at q-value = 0.25. Enriched pathways are color-coded. d Preranked GSEA of the differential gene dependency scores (genome-wide CRISPR screen) between the pseudo-diploid SS48 clone (control) and the aneuploid SS6, SS119 and SS51 clones. Plot presents enrichments for the Hallmark, KEGG, Biocarta and Reactome gene sets. Significance threshold set at q-value = 0.25. Enriched pathways are color-coded. e Comparison of overall drug sensitivity between a near-diploid control clone (SS48), clones with a single trisomy (SS6 and SS119), and clones with multiple trisomies (RPE1-SS51 and RPE1-SS111). Only drugs that led to a viability reduction ranging from −10% to −90% compared to DMSO control (see Methods) were considered. n = 456 drugs. **p = 0.004, ****p = 2.3 * 10−6 and p = 1.2 * 10−8 for WT/Single and WT/Multiple, respectively; Repeated-Measures One-way ANOVA, Tukey’s multiple comparison test. Source data are provided as a Source Data file.
