Loss-of-function MALT1i screen identifies modulators of MALT1i response in ABC-DLBCL. (A) Scheme of screen experimental design. (B) Correlation matrix of normalized shRNA read counts for 2 independent replicate experiments. Gene-set enrichment analysis of a list of “pan-essential genes” in Control vs Input (C) and MI-2–treated vs DMSO-treated cells (D). (E) Plot of gene enrichment MI-2–treated vs DMSO-treated cells ranked by RIGER score. Genes for relevant enriched functional networks are shown. (F) Correlation plot of gene RIGER scores in MI-2–treated cells vs DMSO-treated cells in 2 independent screen replicates. Plotted 500 top and bottom ranked genes (average of 2 replicates). Validation of screen targets using shRNAs against CARD11 (G) or single guide (sg) RNA against TNFAIP3 (H). The effect of gene knockdown on IC₅₀ of MI-2 was assessed by cell count by flow cytometry of live GFP⁺ cells. Gene knockdown was evaluated by western blot. EV, empty vector; shNT, nontargeting shRNA.