Summary
We use our CHyMErA CRISPR screening platform for the mapping of GIs through acute, combinatorial gene perturbation. We designed a GI library targeting genes involved in central metabolism and its regulation, enabling the experimental interrogation for GIs between thousands of gene pairs. We applied this library in human cells cultured in both nutrient-rich and physiologically relevant media. Our pairwise gene knockout screens uncovered dozens of positive and negative GIs between core metabolic enzymes and nutrient transporters, some of which are conditionally dependent on the composition of th
