CRISPR knock-out screens provide a powerful tool with which to investigate highly coordinated cellular processes. Using genome-wide CRISPR knockout screens, followed by focused CRISPR screens, researchers at Boehringer Ingelheim probed the gene-phenotype relationship of human monocyte phagocytosis when the cells were challenged with Staphylococcus aureus. The focused CRISPR screen, which used a custom high-quality guide library synthesized on Twist Bioscience’s DNA synthesis platform, cut the number of candidate genes that needed to be independently tested by 90%, saving Boehringer Ingelheim significant resources throughout their experiment.