Biological systems contain many interconnected components, and it is rare that all components are known for a given process. Therefore, we are using genetic screens with CRISPR-Cas9 to identify the genes that are essential components or regulators of specific cellular processes. To aid in the analysis and interpretation of these screens, we have developed software tools for their processing and analysis (PinAPL-Py; Spahn, Sci Rep, 2017), and integrated the screens with systems biology modeling approaches (Opdam*, Richelle*, Cell Systems, 2017). We also use these to identify regulators of metabolism and the mammalian secretory pathway.