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I would probably collapse overlapping regions with `reduce` to create the second GRanges. Can you add some representative data? Using dput?
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I have one Granges object and not two. Every IRanges entry is the critical region of the gRNA. Can this still work?
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FYI if you also have this problem, this seems to be a pretty good solution: https://github.com/harvardinformatics/degenotate
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