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Fig. 6 | Genome Biology

Fig. 6

From: ZetaSuite: computational analysis of two-dimensional high-throughput data from multi-target screens and single-cell transcriptomics

Fig. 6

Biological insights from identified cancer dependencies. a Cluster (left) and global network (right) for cancer dependencies determined by ZetaSuite from the DRIVE dataset. b, cMYC-associated sub-network, highlighting its connectivity to mediators and Pol II components (b) and ATR connectivity to sub-networks associated with genes involved in DNA conformation or DNA replication/repair (c). Colors correspond to different clusters defined in a. d Functionally enriched GO term biology pathways for cancer checkpoint hits based on the DRIVE dataset. Shown are top 15 GO terms with smallest adjust p-values. e The association of ZetaSuite-identified cancer dependencies with gene expression, copy number, and mutation features. For each gene, cancer cell lines were firstly ranked based on the levels of CNV or gene expression, and the cancer dependency scores were then compared between cell lines in top 25% versus bottom 25%. The p-value (y-axis) for each gene in this comparison was determined by Wilcox-test. In addition, for association analysis with mutations, cancer cell lines were divided in two groups with or without mutation for each gene. The cancer dependency scores were then compared between these two groups and the p-value (y-axis) in this comparison was determined by Wilcox-test. Some representative genes are highlighted in each feature group. Genes above the black dashed line have p-values < 0.05. fTP53-associated sub-network. g Averaged dependency scores for TP53 and MDM2 (top) and TP53 non-mutation frequency (bottom) in different cancer tissues. Tissues are ranked based on averaged TP53 dependency scores. h The TP53 gene dependencies in normal or mutated TP53 cell lines. *** p<0.001 based on Wilcox-test. iCACNA1I gene expression in normal brain tissues (based on the GTEx database) and brain tumors (based on the TCGA database). *** p<0.001 based on Wilcox-test. j Kaplan-Meier survival curves of brain tumor patients associated with high or low CACNA1I expression. The dashed lines indicate the 95% confidence intervals

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