Fig. 5

RNA Methyltransferase Genes Associated with TP53. A Top 10 genes (by differential essentiality log-likelihood ratio) showing increased essentiality in NSCLC cell lines that harbor “damaging” mutations in TP53 (ΔTP53) according to the CCLE, suggesting possible non-oncogene addictions. The RNA m⁶-A methyltransferases METTL14 and METTL16 (green) are of particular interest (see text). B Estimated essentiality of RNA methyltransferase genes in ΔTP53 samples (x-axis) vs. log likelihood ratio in ΔTP53 vs. wild-type TP53 samples (y-axis). C Evaluation of methyltransferase gene essentiality in Project Score CRISPR screens. Only two unique lung-tissue-derived cell lines (3 replicates each) carry wildtype TP53 in the Project Score database, so only two cell lines with a “damaging” mutation in TP53 were selected for comparison using ACE. The cell lines chosen were based on our analysis in the Broad’s Project Achilles, but the data used is generated by screening with a different CRISPR library by the Sanger Institute. The dashed line indicates the empirical p-value cutoff for p<0.05 based on negative controls. D Gene expression data from the CCLE, processed by the Achilles DepMap, for the ΔTP53 cell line panel highlighting the differentially essential methyltransferase genes from panel (B). MDM2 is shown as a positive control and nonessential ZNF366 is shown as a negative control. The distribution of all genes is shown in gray