Fig. 1: CRISPR–Cas9 screen under LSD1 inhibitor treatment.
From: The histone-methyltransferase DOT1L cooperates with LSD1 to control cell division in blast-phase MPN
A Schematic depiction of the workflow to conduct an epigenome-focused CRISPR-Cas9 screen using the EPIKOL-library in HEL cells. B Growth curve of HEL cells treated with Bomedemstat (50 nM), GSK2879552 (50 nM) or DMSO for 14 days during the CRISPR-Cas9 screen (n = 4). C Volcano-plots showing differential dependencies of gene-targets from the EPIKOL-library under LSD1 inhibitor treatment. Beta-scores (x-axis) represent the directionality of gene-effects in the MaGECK-MLE analysis (LSD1 inhibitor vs. DMSO). Genes with negative beta-scores represent synthetic lethal candidates, positive beta scores identify putative resistance mediators. Wald-p-values are plotted on the y-axis. Plots show the results of the analysis of co-vulnerabilities under treatment with Bomedemstat (top) or GSK2879552 (bottom). D Enrichment analysis of Gene-ontology terms (GO cellular component) from positively (red) and negatively (blue) selected gene hits in the CRISPR-Cas9 screen under treatment with Bomedemstat (top) or GSK2879552 (bottom). Analysis was performed using String-db. Size of dots is proportional to the confidence in each term (log10FDR). E Identification of consensus synthetic lethal candidate hits. Schematic of filtering strategy (top) and ranking of consensus hits (bottom). Mean beta score = (betaBomedemstat + betaGSK2879552) / 2.
