My lab developing and applying functional genomics approaches for mapping genetic, and chemical-genetic interactions on a large scale. We developed an automated form of yeast genetics and applied it to the construction of all 18 million yeast double mutants to map ~550,000 negative and ~350,000 positive. A comprehensive set of genetic interaction profiles maps a model of cellular function in which each gene is placed within a functional hierarchy. This model of cell function can be used to interpret chemical-genetic interaction profiles for bioactive compounds, thereby linking them to target bioprocesses and pathways. The global yeast digenic interaction map can be expanded to more complex genetic interactions, such as trigenic interactions, different conditions, and different genetic backgrounds. We are also mapping genetic interaction networks with human cells using newly-developed CRISPR-Cas9 approaches for genome-wide genetic perturbation, and our preliminary results suggest that many of the general principles discovered with the global yeast genetic interaction network are highly conserved. Ultimately, we hope to discover genetic interactions underlying inherited phenotypes in human genotyping data, and we attempting to develop new computational approaches for discovering gene pairs that are associated with human disease.