Extended Data Fig. 4: Focused SPIDR screens in HeLa and K562 cells and independent validation of synthetic lethal gene pairs.
From: Comprehensive interrogation of synthetic lethality in the DNA damage response
a, LFC comparison T14vsT0 for all library elements. b, Volcano plot of log2 fold change of non-targeting (non-targeting:non-targeting) and single gene targeting (targeting:non-targeting) library elements at T14 compared to T0. Statistical significance was determined using the Wald test, with Benjamini-Hochberg post-test. c, Three-way Venn diagram of essential genes shows differential essential genes identified in the three CRISPRi screens. d, Rank order plots of GEMINI sensitive scores in HeLa S3 dCas9-ZIM3 and K562 dCas9-KRAB cells from the focused SPIDR screens. e, Three-way Venn diagram showing the intersection of synthetic lethal interactions identified in the three CRISPRi screens. Hits are listed in supplementary table 4. f, Stringently filtering for only the strongest synthetic relationships (GEMINI sensitive score ≤−2.5) in RPE-1 cells reveals two unanticipated synthetic lethal modules: WDR48 (also known as UAF1) with LIG1 and FEN1, and SMARCAL1 with FANCM and C19orf40/FAAP24. g, Dual-color flow cytometry assay performed in HeLa S3 dCas9-ZIM3 and K562 dCas9-KRAB cells. The log2 fold changes relative to day 0 are shown. Day 10 values are shown for all pairs except for FEN1:WDR48 (in K562 cells), where day 7 values are shown due to complete dropout of the double transduced population. Error bars represent mean ± s.d. 3 technical replicates are shown.
