Evaluation of RNAi and CRISPR technologies by large-scale gene expression profiling in the Connectivity Map
Fig 3
CGS enhances on-target signal and mitigates off-target effects.
(A) For directly-measured landmark transcripts targeted by RNAi, cumulative distribution of the rank of that transcript in the resulting signature when using either the signature produced by an individual shRNA or the CGS. (B) Cumulative distribution plot of the change in the correlation to the CGS for either individual shRNAs that target the gene or for shRNAs that share the same seed as one of the shRNAs that contributed to the CGS. (C) For individual leave-one-out shRNAs, comparison of the correlation to the CGS and the analogous CSS. The density color scale is linear. (D) Comparison of on- and off-target activity across cell lines. Top left: for each shRNA in A375 cells, the plot shows the correlation between CGS (x-axis) and CSS (y-axis). Those in red have minimal off-target effects (CSS Spearman correlation <|0.2|) and substantial on-target effects (CGS Spearman correlation >0.15). Remaining panels: the red-highlight shRNAs from A375 cells are highlighted in red in 3 other cell lines. CSS, consensus seed signature; CGS, consensus gene signature; RNAi, RNA interference; shRNA, short hairpin RNA.
doi: https://doi.org/10.1371/journal.pbio.2003213.g003