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We propose the Model-based Analysis of Genome-wide CRISPR/Cas9 Knockout (MAGeCK) method for prioritizing single-guide RNAs, genes and pathways in genome-scale CRISPR/Cas9 knockout screens. MAGeCK demonstrates better performance compared with existing methods, identifies both positively and negatively selected genes simultaneously, and reports robust results across different experimental conditions. Using public datasets, MAGeCK identified novel essential genes and pathways, including  EGFR  in vemurafenib-treated A375 cells harboring a  BRAF  mutation. MAGeCK also detected cell type-specific essential genes, including  BCR  and  ABL1 , in KBM7 cells bearing a  BCR-ABL  fusion, and  IGF1R  in HL-60 cells, which depends on the insulin signaling pathway for proliferation.   Electronic supplementary material  The online version of this article (doi:10.1186/s13059-014-0554-4) contains supplementary material, which is available to authorized users.

MAGeCK enables robust identification of essential genes from genome-scale CRISPR/Cas9 knockout screens