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. 2022 Jul 22;13:4240. doi: 10.1038/s41467-022-31801-7

Fig. 4. Genome-wide CRISPR/Cas9 screens in WT and TDP1-KO cells with TOP1 poison.

Fig. 4

a Ranking of CPT co-essential genes on the basis of drug Z analysis of the results of CRISPR/Cas9-based screening in HEK293A-WT cells. The z-score was used to define a possible synthetic lethal interaction with CPT. All genes targeted by the Toronto Knock Out Library v3 were scored according to the fold change of levels of their sgRNAs. The CPT-treated group and not treated (NT) group in WT cells were compared. Genes whose loss of function led to CPT sensitivity appear on the left side, with a minus Z score, and genes whose loss of function led to CPT resistance appear on the right side, with a positive Z score. Top-ranked genes on either side are marked. b Ranking of CPT co-essential genes on the basis of a drug Z analysis of the results of CRISPR/Cas9-based screening in TDP1-KO cells. Data were analyzed and presented as in a. The CPT-treated group and NT group in TDP1-KO cells were compared. c Combinational comparison of CPT co-essential genes between HEK293A-WT and TDP1-KO cells. The z-scores from a, b were used. d A p value is calculated from the normZ and corrected for multiple hypothesis testing using the method of Benjamini and Hochberg. KEGG pathway analysis of genes whose loss of function led to CPT sensitivity (p < 0.01) in WT and TDP1-KO cells was performed with DAVID Bioinformatics Resources 6.8, NIAID/NIH (https://david.ncifcrf.gov/summary.jsp). e Ranking of TDP1 co-essential genes on the basis of a drug Z analysis of the results of CRISPR-/Cas9-based screening. The z-score was used to define a possible synthetic lethal interaction with TDP1. All genes targeted by the Toronto Knock Out Library v3 were scored according to the fold change of their sgRNA levels. The NT TDP1-KO cell group and NT WT cell group were compared. f A combinational comparison was performed of TDP1 co-essential genes between HEK293A-WT and TDP1-KO cells using the z-score of the NT TDP1-KO cell group compared to the NT WT group and the CPT-treated TDP1-KO group compared to the CPT-treated WT group.