Extended Data Fig. 8: Signaling and impact of subtle differences in editing efficiency and phenotypic readouts.
From: Mapping variant effects on anti-tumor hallmarks of primary human T cells with base-editing screens
a, Quantification of S6 phosphorylation (pS235/S236) and b, AKT phosphorylation (pS473) measured by flow cytometry in T cells with indicated genotypes (x axis) after 10 minutes of stimulation with anti-CD3/CD28 antibodies. c, For all validated sgRNAs targeting PIK3CD (that is, Cys416Arg, Tyr524Cys, Glu525Gly_His526Arg, and Glu527Gly_Lys528Glu), sgRNA editing efficiency and effect size on AKT phosphorylation (pS473), d, TNFα MFI, and e, IL2 expression are plotted for each of the 3 donors used in initial validation experiments in Fig. 3. In cases where sgRNAs generated multiple edits within the editing window (for example, PIK3CD Glu525Gly_His526Arg), the average editing efficiency across all targeted bases in the editing window was used. Data in (a-b) was generated from n = 3 independent human donors. Within each donor this data was normalized to the silent control condition. One-way ANOVA with Dunnett’s test for multiple comparisons (panels a,b). Simple linear regression (panels c-e). Error bars represent mean +/− SD (panels a, b).
