When most people think about how a mutation impacts phenotype, they think about changes at the organismal level. Does it predispose an individual to disease? Does it help bacteria resist drugs? But that’s not the whole story…

Every mutation has an impact at the molecular level, for example, by changing the level of a transcript or the fold of a protein. These effects fan out to influence other phenotypes, ultimately causing changes at the level of cells and organisms. The KGS lab focuses on this wider view by tracing the impact of mutations through what we call the genotype-phenotype-phenotype-phenotype map.

To study this map, we merge high-throughput experiments in yeast with computational and mathematical approaches. We observe how the impacts of mutations change in similar ways across contexts, and use similarities to build predictive models. Predicting the impacts of genotype on phenotype remains one of the most important goals in all of science.