Fig. 6

Accurate predictions of guide activity. a Highly active guides against essential genes bind ~ 50 bp upstream of the transcription start site. The fitness effect produced by guides targeting essential genes serves as a proxy for their activity. Individual guides targeting non-divergent essential genes with at least two independent barcodes are plotted according to their position, fitness effect, and absolute chromatin occupancy as determined by DNA methylation accessibility, along with a local regression of fitness effect against position. b Guide activity varies according to the guide strand, as seen in local regressions for guides on the same (Fwd) or opposite (Rev) strand as the target gene. c Receiver operating characteristic for logistic regression models of guide activity. The full model includes methylation-based accessibility data (ODM-Seq) and guide sequence along with the position of the guide relative to the transcription start site. d Guide score predicts fitness effects in a held-out test set of guides targeting essential genes