Fig. 5
Effect of target location and accessibility on gRNA efficacy. In all plots gRNA efficacy was measured in the presence of the appropriate reference small molecule. a gRNA effect magnitude (absolute value of gRNA effects that were censored to have a maximum of 0) is plotted on the y-axis, against target position relative to the TSS on the x-axis. The median in 50 bp windows (solid line, big markers), overlapping by 25 bp, indicates a region of 200 bp immediately upstream the TSS as effective. b gRNA effect magnitude is plotted on the y-axis, against target position (gRNA midpoint) relative to the TSS on the x-axis for four loci (indicated above each plot). gRNAs targeting template and non-template strands are indicated with ‘o’ and ‘x’, respectively. Standard deviation estimates are indicated with blue lines, and maximum estimated gRNA effect magnitude for each target locus is given as a gray dashed line. Nucleosome occupancy (red line), and smoothed ATAC-seq read density (green line) relative to the region maximum are scaled to the maximum effect magnitude. c gRNA effects (y-axis) are plotted (black dots) against nucleosome occupancy score (x-axis, left) and ATAC-seq read density (x-axis, right). The median of gRNA effects in windows of 0.25, overlapping by 0.125, is indicated by the circular blue markers. The blue bars show the first and third quartiles. The Spearman correlation for the relationship with nucleosome density is 0.34, P value = 9.6 × 10-12. The Spearman correlation for the relationship with normalized ATAC-Seq is -0.35, P value = 2.2 × 10-12