Fig. 7

Single-mismatch tolerance and genetic interactions in the Achilles dataset. a Cumulative distribution of off-target delta coefficients for the set of 427 guides that have exactly one on-target and one single-mismatch off-target in the Avana library. Larger negative coefficients suggest greater off-target activity. The gray line represents the cumulative distribution of delta coefficients for 1000 guides chosen at random. b Log-fold changes (LFCs) for guides targeting seven pairs of paralog genes. Clean guides and double-target guides are shown. c Avana guide design for guides targeting LSM14A and LSM14B. d LFCs and CERES scores for guides targeting LSM14A and LSM14B. Notation: LFC (A;B): LFC for a guide with gene A as an on-target and gene B as a single-mismatch off-target. e Same as c, for YPEL1 and YPEL3. f LFCs and CERES scores for guides targeting YPEL1 and YPEL1. Colors indicate gene-specific cell line dependencies. Red: YPEL1-only dependencies; black: YPEL3-only dependencies; orange: both YPEL1 and YPEL3 dependencies; blue: no dependencies. g Same as c, for SLC25A18 and SLC25A22. h LFCs and CERES scores for guides targeting SLC25A18 and SLC25A22. Right panel: LFC averaged across all on-target guides targeting SLC25A18 and SLC25A22 vs LFC averaged across guides with both on-targets and off-targets. Red: SLC25A18-dependent cell lines. Orange: SLC25A22-dependent cell lines. Black: no dependencies