Fig. 5
The effects of single-mismatch sgRNA-DNA tolerance on gene essentiality. a On the left: CERES score for SOX9 plotted against SOX9 expression; each dot is a cell line, and cell lines highly expressing SOX10 (log2(rpkm+1)≥4) are colored in red. The curve represents a LOWESS estimated with cell lines lowly or not expressing SOX10 (gray dots). On the right: CERES score for SOX9 plotted against SOX10 expression. b Guide design for guides targeting SOX9 and SOX10 in the Avana library. c Log-fold changes (LFCs) of guides targeting SOX9 and SOX10 as a function of SOX9 expression. Curves represent LOWESS fit estimated with cell lines lowly or not expressing SOX10 (gray dots). d Comparison of single-mismatch tolerant and intolerant guides targeting SOX9 and SOX10eBRAF-associated coessentiality cluster using between-gene CERES Pearson correlations. A correlation cutoff of r=0.35 was chosen to draw edges. Edges associated with SOX9 (orange) disappear when excluding SOX9-targeting guides with single-mismatch tolerant SOX10 off-targets (dark gray indicates lines with high SOX9 expression). f Pearson correlations between the SOX9’s CERES score and CERES scores for genes that are part of BRAF-associated cluster, before and after removal of SOX9-targeting guides with single-mismatch tolerant SOX10 off-targets