Functional genomics using CRISPR-Cas systems for saturating mutagenesis of non-coding elements, compositions, methods, libraries and applications thereof

A deep scanning mutagenesis library to interrogate phenotypic changes in a population of cells comprising a plurality of Type II CRISPR-Cas system guide RNAs comprising guide sequences, each guide sequence capable of targeting a non-coding genomic sequence within at least one continuous genomic region, wherein the plurality of guide RNAs target at least 100 genomic non-coding sequences comprising non-overlapping cleavage sites upstream of a PAM sequence for every 1000 base pairs within the at least one continuous genomic region and wherein the plurality of guide RNAs are capable of targeting two or more continuous genomic regions that physically interact, the at least one continuous genomic region comprising noncoding sequences, and wherein the guide RNAs have a median adjacent genomic cleavage distance between 4 bp and 20 bp.