Fig. 6: Off-target profile of the STGD-gRNA on human retinal and RPE/choroid explants.
From: High-efficiency base editing in the retina in primates and human tissues
a,b, Circos plots visualizing the off-target profile of the STGD-gRNA. Each sector in the circos plot corresponds to one chromosome that is indicated by the number in the outermost track. The second track shows the results from the ONE-seq assay with the bars representing the counts per million (CPM) for each genomic site. The green bar corresponds to the on-target site, and the red bars represent off-target sites for which the CPM passed the assay threshold of 200 CPM. The innermost track shows the targeted sequencing results of the sites nominated by the ONE-seq assay as well as sites with ≤3 mismatches to the STGD-gRNA, from human retinal explants (a; 399 genomic sites; 811 adenine base-editing positions) and RPE/choroid explants (b; 401 genomic sites; 812 adenine base-editing positions) treated with AAV5-v2-SABE1. The logarithm of base 2 of the odds ratio (log2(OR)) quantifying the A-to-G enrichment at each genomic site in the treated samples is plotted along the vertical axis of the track. Statistical significance was determined by Fisher’s exact test and expressed as −log10 P value. The on-target site, for which the logarithm of the OR was significant (−log10(P value) > 20), is colored in green. Sites for which the enrichment was not significant (−log10(P value) < 20) are colored in gray. Illustrations in a and b created with BioRender.com.
