Journal: Genome Medicine
Article Title: Genome-aware annotation of CRISPR guides validates targets in variant cell lines and enhances discovery in screens
doi: 10.1186/s13073-024-01414-4
Figure Lengend Snippet: Assessment of Addgene pooled CRISPR-spCas9 libraries for human and mouse. A Library guides were re-annotated with Exorcise using genome assembly GRCh38 (human) or GRCm38 (mouse). Re-annotations were compared with original annotations to identify off-target effects, missed-target effects, and boundary effects. B Mis-annotations identified by Exorcise. Other-locus off-target effects are caused by multiple targeting of guides to multiple loci. Same-locus off-target effects are caused by multiple knockouts by a guide due to overlapping features at a single locus. False non-targeting effects are missing annotations of a valid guide target. Missed-target effects are caused by a library guide being mis-annotated as targeting. Boundary effects are caused by mis-annotations with adjacent exons or genes. C Performance of Addgene libraries. Library guides were analysed with Exorcise with RefSeq exons. Bars indicate the proportion of guides which have any off-target effects (peach), any missed-target effects (cyan), or only on-targets (green). D Distribution of VBC scores among Addgene libraries. Dashed line indicates the median VBC score across all guides in all libraries. E Off-target effects of library guides in Addgene libraries. Distribution of number of off-target effects per guide by library. Inset: distribution of other-locus and same-locus off-target effects by library. F Missed-target effects in Addgene libraries. Distance between Cas9 cut site, if any, and the nearest exon in linear distance in nucleotides. Inset: zoom plot between 0 and 50 nucleotides
Article Snippet: D Distribution of VBC scores among Addgene libraries.
Techniques: CRISPR
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