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. 2022 Jun 23;11:e72879. doi: 10.7554/eLife.72879

Figure 3. DUB essentiality and codependency relationships in DepMap.

(A) The fraction of cancer cell lines present in the DepMap that are strongly dependent on each DUB (using recommended threshold CERES <–0.5). Bars are colored coded based on knockout mouse phenotype data from the IMPC and MGI datasets. (B) The strongest co-dependent genes for each DUB (n=7 but similar results were obtained for n=5–10). For visualization purposes, only DUBs that either had a significantly enriched GO term, a co-dependent gene supported by PPID or CCLE proteomics co-expression, or scored as essential in at least 20% of DepMap cell lines are displayed (see Supplementary files 6 and 7 for complete codependency results). The inner ring (ring 1) contains the top GO term for the co-dependent genes for each DUB (highly similar GO terms are grouped to aid in viewing the data, see Supplementary file 5 for all GO results). The second ring contains the DUB gene name. The third ring contains the fraction of cell lines strongly dependent on the DUB. The fourth ring contains the co-dependent gene name (green if DUB – co-dependent gene pair exists in a protein-protein interaction database). The fifth ring contains the Pearson correlation value for the DUB-co-dependent gene pair (red represents a positive correlation and blue represents a negative correlation). The sixth ring designates which co-dependent genes had similar transcriptomic profiles in CMap or were co-expressed in baseline proteomics with the respective DUB.

Figure 3.

Figure 3—figure supplement 1. Differential DUB dependency by cancer type.

Figure 3—figure supplement 1.

Two-sided t-tests were conducted between a selected cancer type and all other cell lines for each DUB knockout (plotted as difference in mean dependency score vs adjusted p-value, adjusted p-value <0.1 colored red). Negative difference in means represents a cancer type with increased dependence on that knockout (stronger impact on proliferation) and a positive difference in means represents a cancer type with decreased dependence on that knockout (weaker impact on proliferation).
Figure 3—figure supplement 2. Assessing the association between DUB abundance and dependency.

Figure 3—figure supplement 2.

(A) Correlations between the impact of DUB knockout on proliferation (CERES dependency score) and DUB copy number, mRNA abundance, and protein abundance for each DUB. A negative correlation occurs when the DUB abundance is higher in the more sensitive cells and a positive correlation occurs when the DUB abundance is lower in the more sensitive cells. (B) The fraction of each tumor type in the DepMap with copy number loss of the eleven DUBs with correlations between copy number and sensitivity to DUB knockout greater than 0.2. (C) The fraction of all cell lines with copy number loss of the eleven DUBs with correlations between copy number and sensitivity to DUB knockout greater than 0.2.
Figure 3—figure supplement 3. Copy number loss of individual DUBs in various tumor types.

Figure 3—figure supplement 3.

(A) The fraction of each tumor type in TCGA PanCancer Atlas studies with copy number loss of individual DUBs. The eleven DUBs with correlations between copy number and sensitivity to DUB knockout greater than 0.2 in the DepMap are displayed. (B) The fraction of all tumor types with copy number loss of the 11 DUBs with correlations between copy number and sensitivity to DUB knockout greater than 0.2. (C) Abbreviations for TCGA tumor types.
Figure 3—figure supplement 4. Enrichment of interactors and co-expressed genes in co-dependent genes.

Figure 3—figure supplement 4.

(A) The number of co-dependent genes sorted by correlation value supported by protein-protein interactions (red) compared to the number supported when co-dependent genes are randomly shuffled (black). (B) The number of co-dependent genes sorted by correlation value supported by co-expression (red) compared to the number supported when co-dependent genes are randomly shuffled (black).
Figure 3—figure supplement 5. Enriched GO terms that are common across analyses.

Figure 3—figure supplement 5.

(A) The significant GO terms from the DepMap co-dependent gene analysis were compared to GO terms enriched in the interactors for each DUB and the co-expressed proteins in the Cancer Cell Line Encyclopedia proteomics dataset. (B) The most significant GO term from DepMap analysis (smallest FDR <0.05) for each DUB as well as the GO term from DepMap analysis with the largest sum of -log(p-value) across datasets (if different). DUBs that were not present in the dataset are distinguished with a black dot.