Quantitative approaches to study phenotypic effects of large-scale genetic perturbations

How microbes interact with their environment and how the complex interplay of their genes enables them to survive and thrive under stress is a fundamental question in microbial system biology, which is also important from a public health perspective. Large-scale studies of gene-gene, gene-drug, and drug-drug interactions have proven to be powerful tools for elucidating gene function and functional modules in the cell. Approaches that systematically quantify phenotypes in libraries of microbial strains with genome-wide genetic perturbations are crucial for progress in this area. Here, we review recent advances in this field, and point out applications to the study of gene-drug interactions. We highlight newly developed techniques for the rapid generation of genome-wide mutant libraries and the high-throughput measurement of more complex phenotypes and other observables, such as cell morphology or thermal stability of the proteome.