Extended Data Fig. 2: Treatment-related conditional genetic interactions in pGBM.
From: Targeting axonal guidance dependencies in glioblastoma with ROBO1 CAR T cells
(a) Schematic for identification of conditional genetic interactions (cGIs) in pGBM BT594. Tumor cells were infected with genome-wide CRISPR-Cas9 gene knockout library (TKOv3) and exposed to DMSO, sublethal radiation therapy (RT), sublethal TMZ or combination treatment (RT & TMZ) over 15-18 doublings. Illumina sequencing and subsequent analyses (gRNA fold change and Z score computation) of cellular populations at beginning and end of each screen identified cGIs. (b) Gene-level LFC of CEGs and non-essential genes across screens in pGBM BT594 cells. All data presented from n = 3 biologically independent replicates. P values are from unpaired Student’s t tests. Median value at centre with lower and upper hinges at 1st (25th) and 3rd (75th) quartiles, respectively. Whiskers extend from hinge to 1.5*IQR. (c) Precision-recall plots of BT594 screens. (d) Comparison of cGI Z scores computed by measuring gene-level LFC from screens in rGBM BT972 or drug-treated pGBM cells compared to untreated pGBM cells. Pearson correlation coefficients and P values shown for each pairwise comparison with (black) and without (grey) filtering for genes that meet FDR <0.05 in at least one screen.
