CRISPR genomic screening informs gene–environment interactions

Gene–environment interactions impact the adverse health effects of environmental exposure to toxicants. Identification of genetic factors modulating organismal and cellular response to environmental toxicants can inform risk assessment. Genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)–based genetic perturbation screening has recently emerged as a powerful approach to illuminate complex cellular processes including mechanisms modulating chemical toxicity. Here, we review key studies that demonstrate the utility of CRISPR screens in deciphering the molecular determinants of sensitivity and tolerance to toxic substances. We reflect on key considerations for implementing a CRISPR screen in toxicology. We also discuss computational methods used for analyzing CRISPR screens and strategies for validating screening results. Finally, we highlight potential future directions to address limitations in CRISPR screening approaches as applied to toxicology.