Quantitative and multiplexed chemical-genetic phenotyping in mammalian cells with QMAP-Seq.

ABSTRACT: Chemical-genetic interaction profiling in model organisms has proven powerful in providing insights into compound mechanism of action and gene function. However, identifying chemical-genetic interactions in mammalian systems has been limited to low-throughput or computational methods. Here, we develop Quantitative and Multiplexed Analysis of Phenotype by Sequencing (QMAP-Seq), which leverages next-generation sequencing for pooled high-throughput chemical-genetic profiling. We apply QMAP-Seq to investigate how cellular stress response factors affect therapeutic response in cancer. Using minimal automation, we treat pools of 60 cell types-comprising 12 genetic perturbations in five cell lines-with 1440 compound-dose combinations, generating 86,400 chemical-genetic measurements. QMAP-Seq prod

SUBMITTER: Brockway S 

PROVIDER: S-EPMC7661543 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature