A chemical-genetic interaction map of small molecules using high-throughput imaging in cancer cells

ABSTRACT: Small molecules often affect multiple targets, elicit off-target effects and induce genotype-specific responses. Chemical genetics, the mapping of the genotype-dependence of a small molecule’s effects across a broad spectrum of phenotypes can identify novel mechanisms of action. It can also reveal unanticipated effects and could thereby reduce high attrition rates of small molecule development pipelines. Here, we used high-content screening and image analysis to measure effects of 1280 pharmacologically active compounds on complex phenotypes in isogenic cancer cell lines which harbor activating or inactivating mutations in key oncogenic signaling pathways. Using multiparametric chemical-genetic interaction analysis, we observed phenotypic gene–drug interactions for more than 193 compounds,

ORGANISM(S): Homo sapiens

SUBMITTER: Marco Breinig 

PROVIDER: S-BSMS-PGPC1 | bioimages | 2015

REPOSITORIES: bioimages