Fig. 5

Paralog compensation is an important feature shaping tissue-specific aneuploidy patterns. A The correlation between paralog compensation values and loss frequency of chromosome arms in primary tumors (left, ρ = 0.26, adjusted p = 0.18, Spearman correlation) and in CCLs (right, ρ = 0.46, adjusted p = 0.01, Spearman correlation). B A view into the aneuploidy patterns of paralogs of recurrently lost genes. Recurrently lost genes were divided into essential, intermediate, and non-essential groups. Paralogs of essential genes were more frequently gained, whereas paralogs of non-essential genes were more frequently lost. C Genome-wide comparison of differentially essential genes in colorectal cell lines with chr13q gain (n = 39) versus chr13q-WT colorectal cell lines (n = 25). On the right side are the genes that are more essential in chr13q-WT cells, and on the left side those that are more essential in chr13q-gain cells, based on a genome-wide CRISPR/Cas9 knockout screens [39]. The x-axis presents the effect size (i.e., the differential response between chr1q-WT and chr13q-gain colorectal cell lines) and the y-axis presents the significance of the difference (-log10(p-value)). UCHL1 (in red) is one of the top genes identified to be more essential in chr13q-WT cells. D Comparison of the sensitivity to CRISPR knockout of UCHL1 between colorectal cell lines with (n = 28) and without chr13q gain (n = 16). ***, p = 0.0003; two-tailed Mann–Whitney test. E Comparison of UCHL3 mRNA expression between colorectal cell lines with (n = 34) and without chr13q gain (n = 23). ****, p < 0.0001; two-tailed Mann–Whitney test. F Correlation between UCHL3 mRNA expression and the sensitivity to UCHL1 knockout, showing that higher UCHL3 mRNA levels are associated with reduced sensitivity to UCHL1 knockout. ρ = 0.28, p = 0.041; Spearman correlation. G Comparison of the prevalence of chr4p loss between human primary colorectal tumors with and without chr13q gain. ****, p < 0.0001, Chi-square test. H Comparison of the prevalence of chr4p loss between human colorectal cancer cell lines with and without chr13q gain. ****, p < 0.0001, Chi-square test