Fireworks

Coessential Genetic Networks Reveal the Organization and Constituents of a Dynamic Cellular Stress Response. Summary The interrelated programs essential for cellular fitness in the face of stress are critical to understanding tumorigenesis, neurodegeneration, and aging. However, modelling the combinatorial landscape of stresses experienced by diseased cells is challenging, leaving functional relationships within the global stress response network incompletely understood. Here, we leverage genome-scale fitness screening data from 625 cancer cell lines, each representing a unique biological context, to build a network of “coessential” gene relationships centered around master regulators of the response to proteotoxic, oxidative, hypoxic, and genotoxic stress.