Extended Data Fig. 3: Genome-wide 2D and 3D CRISPR screens in H2009, a lung adenocarcinoma line with KRASG12A mutation.
From: CRISPR screens in cancer spheroids identify 3D growth-specific vulnerabilities
a, Distributions of 2D and 3D phenotypes are shown as volcano plots. The y axis represents absolute T-score for each gene, and the x axis represents effect size of each gene. Size of dots represents absolute T-score of genes. b, Prediction of TSGs or oncogenes with 2D, 3D and 3D/2D phenotypes in H2009 cells. Cumulative sums of TSG counts (top) or oncogene counts (bottom) are plotted against genes sorted by their 2D, 3D or 3D/2D phenotypes (T-score) from the genome-wide screens in H2009 cells. These data indicate that 3D phenotypes, and in particular the differential 3D/2D phenotypes show improved prediction of both TSGs and oncogenes when compared with 2D phenotypes. In the box plots, centre lines mark median, box limits mark upper and lower quartiles, whiskers show 1.5× interquartile range and points indicate outliers. c, Enriched pathways among the top 1,000 hits from each culture condition were analysed using PANTHER overrepresentation test. Significance of enriched pathways was measured with Fisher’s Exact test and the Benjamini–Hochberg FDR was subsequently computed (x axis). The Ras pathway, a known driver for H2009 cells, is enriched in 3D/2D phenotypes. Numbers of genes for enriched pathways are marked to the right of bars. d, The cumulative sum of the significance of 11,249 pan-lung cancer mutations from 1,144 patients with lung cancer as measured by MutSig2CV is displayed on the y axis, while the x axis shows phenotypes for genes sorted by their strength in 2D (solid red line), 3D (solid blue line) or 3D/2D (solid yellow line). Black dotted line, randomly sorted genes. Top 3,000 genes are shown.
