@article {1133711, title = {Pooled genome-wide CRISPR screening for basal and context-specific fitness gene essentiality in cells}, journal = {Elife}, volume = {7}, year = {2018}, month = {2018 07 27}, abstract = {Genome-wide screens in cells have offered numerous insights into gene function, yet a major limitation has been the inability to stably deliver large multiplexed DNA libraries to cultured cells allowing barcoded pooled screens. Here, we developed a site-specific integration strategy for library delivery and performed a genome-wide CRISPR knockout screen in S2R+ cells. Under basal growth conditions, 1235 genes were essential for cell fitness at a false-discovery rate of 5\%, representing the highest-resolution fitness gene set yet assembled for , including 407 genes which likely duplicated along the vertebrate lineage and whose orthologs were underrepresented in human CRISPR screens. We additionally performed context-specific fitness screens for resistance to or synergy with trametinib, a Ras/ERK/ETS inhibitor, or rapamycin, an mTOR inhibitor, and identified key regulators of each pathway. The results present a novel, scalable, and versatile platform for functional genomic screens in invertebrate cells.}, keywords = {Animals, Computational Biology, CRISPR-Cas Systems, Drosophila, Drug Interactions, Gene Expression Regulation, Gene Knockout Techniques, Gene Library, Genes, Essential, Genetic Fitness, Genome-Wide Association Study, Pharmacogenetics, Phenotype, Protein Kinase Inhibitors, Pyridones, Pyrimidinones, Sirolimus}, issn = {2050-084X}, doi = {10.7554/eLife.36333}, author = {Viswanatha, Raghuvir and Li, Zhongchi and Hu, Yanhui and Perrimon, Norbert} }