Skip to main content
. 2022 Dec 28;13(3):766–795. doi: 10.1158/2159-8290.CD-22-1230

Figure 1.

Figure 1. Cell type-specific role of the UBA6/BIRC6/KCMF1/UBR4 module revealed by the coessentiality analysis. A, Based on the significance of correlation and the variance of essentiality, we selected 50 top coessential gene modules, which included 42 modules for which the functional interactions of the constituent genes have already been reported (green dots) and eight modules that contain previously unassociated gene pair(s) (pink dots). B, Correlation of the essentiality of the four genes that comprise the BIRC6 module (UBA6, BIRC6, KCMF1 and UBR4). The Pearson correlation coefficients between the dependency profiles of the indicated gene pairs in both CRISPR (top) and RNAi (bottom) datasets (left) are shown. The correlations between UBA6 and BIRC6 (r = 0.714) as well as KCMF1 and UBR4 (r = 0.742) in the CRISPR dataset are also shown individually in the scatter plots (right). C, All these genes exhibited dependency profiles with both high variance (> 89th percentile among all genes) and strong efficacy (> 83rd percentile of all genes), the latter being defined by the minimum dependency score (Chronos) across all cell lines. D, The dependency profiles of the four genes constituting the BIRC6 module. UBA6 and BIRC6 were strongly essential (> 90% probability of dependency) in a small subset of cell lines, while KCMF1 and UBR4 were strongly essential in the majority (> 65%) of cell line models. E, Dependency on the BIRC6 module per tissue type. The mean Chronos (mChronos) scores of the four genes comprising the BIRC6 module were plotted per tissue type. The dependency on this module is enriched in epithelial tissue–derived cancer cells. F, Significance of the lineage/subtype enrichment of the BIRC6 module gene dependencies in the CRISPR and RNAi screens. The distribution of mChronos or mean DEMETER2 scores in the individual lineages/subtypes was compared with the corresponding distribution in all the other cell lines within the dataset. The effect size and significance, determined by the two-sample Kolmogorov–Smirnov test, were plotted.

Cell type–specific role of the UBA6/BIRC6/KCMF1/UBR4 module revealed by the coessentiality analysis. A, Based on the significance of correlation and the variance of essentiality, we selected 50 top coessential gene modules, which included 42 modules for which the functional interactions of the constituent genes have already been reported (green dots) and eight modules that contain previously unassociated gene pair(s) (pink dots). B, Correlation of the essentiality of the four genes that comprise the BIRC6 module (UBA6, BIRC6, KCMF1, and UBR4). The Pearson correlation coefficients between the dependency profiles of the indicated gene pairs in both CRISPR (top) and RNAi (bottom) datasets (left) are shown. The correlations between UBA6 and BIRC6 (r = 0.714) as well as KCMF1 and UBR4 (r = 0.742) in the CRISPR dataset are also shown individually in the scatter plots (right). C, All these genes exhibited dependency profiles with both high variance (>89th percentile among all genes) and strong efficacy (>83rd percentile of all genes), the latter being defined by the minimum dependency score (Chronos) across all cell lines. D, The dependency profiles of the four genes constituting the BIRC6 module. UBA6 and BIRC6 were strongly essential (>90% probability of dependency) in a small subset of cell lines, while KCMF1 and UBR4 were strongly essential in the majority (>65%) of cell line models. E, Dependency on the BIRC6 module per tissue type. The mean Chronos (mChronos) scores of the four genes comprising the BIRC6 module were plotted per tissue type. The dependency on this module is enriched in epithelial tissue–derived cancer cells. F, Significance of the lineage/subtype enrichment of the BIRC6 module gene dependencies in the CRISPR and RNAi screens. The distribution of mChronos or mean DEMETER2 scores in the individual lineages/subtypes was compared with the corresponding distribution in all the other cell lines within the dataset. The effect size and significance, determined by the two-sample Kolmogorov–Smirnov test (KS), were plotted. ERpos, estrogen receptor positive; Her2Amp, Her2 amplified; TNBC, triple-negative breast cancer.