Abstract: A system for selecting CRISPR guides for knocking out one or more target genes in a target cell from a multiplicity of candidate guides comprises a memory and a processor. The processor determines whether the candidate guide meets a plurality of thresholds. The thresholds are associated with: a transcript support level; targeting a consensus sequence of a target gene; which exon of the target gene is targeted; targeting of a primary transcript, targeting of a common isoform; a precomputed prediction of editing outcomes; mapping to an expressed sequence; fraction of gene expression attributable to targeted transcripts; a common SNP overlap threshold; which exon of the target gene is targeted; overlap of a selected guide; predicted frameshift percentage; maximum and minimum GC content; off target score; where a coding sequence is targeted. In response to meeting the thresholds, the processor selects the candidate guide as a selected CRISPR guide.