An improved statistical method to identify chemical-genetic interactions by exploiting concentration-dependence.

ABSTRACT: Chemical-genetics (C-G) experiments can be used to identify interactions between inhibitory compounds and bacterial genes, potentially revealing the targets of drugs, or other functionally interacting genes and pathways. C-G experiments involve constructing a library of hypomorphic strains with essential genes that can be knocked-down, treating it with an inhibitory compound, and using high-throughput sequencing to quantify changes in relative abundance of individual mutants. The hypothesis is that, if the target of a drug or other genes in the same pathway are present in the library, such genes will display an excessive fitness defect due to the synergy between the dual stresses of protein depletion and antibiotic exposure. While assays at a single drug concentration are susceptible to no

SUBMITTER: Dutta E 

PROVIDER: S-EPMC8486102 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature