Extended Data Fig. 3: Comparative CRISPR screens across 9 ADs.
(a) Schematic of the screening strategy used to identify the cofactors required for each AD. Dropout analysis assesses the guides depleted over time in the screen to identify cofactors required for cell viability. (b) STRING analysis on the highest stringency setting using all the genes classified as a hit for at least one of the ADs. (c) Heatmap of the fold enrichment for all of the genes classified as a hit across any of the 9 AD screens. n = 239 genes. (d) Heatmap of fold enrichment for the genes defined as essential for cell viability based on dropout analysis of day 14 samples. n = 230 genes. (e) Correlation between the average fold enrichment and average effect on cell growth (across all cell lines in the DEPMAP database). Components of the RNA polymerase 2 complex are labelled. Genes in red box with blue dot are required for cell viability, but not enriched in any AD screen. n = 239 genes which are hits. (f) Quantification of the change in representation (guide counts) for essential genes and non-essential genes at each of the screen timepoints. Essential genes defined using day 14 samples, same list as (d). n = 230 essential genes. Line extends from minima to maxima, with box representing 25th percentile, 50th percentile, 75th percentile. (g) Quantification of the change in representation (guide counts) for essential genes and non-essential genes at each of the screen timepoints. Essential genes defined using DEPMAP database. Any gene with an average reduction of −0.5 across all cell lines in DEPMAP was defined as essential. n= ~2000 genes. Line extends from minima to maxima, with box representing 25th percentile, 50th percentile, 75th percentile. (h) Coefficient of variation of essential and non-essential genes across the 9 AD screens. Genes defined as essential by either day 14 dropout (left) (n = 230 genes) or DEPMAP (right) (n= ~2000 genes). > indicates that non-essential genes are higher than essential genes. n.s. = not significant, *=p-value < 0.05, paired two-sided t-test. Line extends from minima to maxima, with box representing 25th percentile, 50th percentile, 75th percentile.
