Multidimensional drug profiling by automated microscopy.
We present a method for high-throughput cytological profiling by microscopy. Our system provides quantitative multidimensional measures of individual cell states over wide ranges of perturbations. We profile dose-dependent phenotypic effects of drugs in human cell culture with a titration-invariant similarity score (TISS). This method successfully categorized blinded drugs and suggested targets for drugs of uncertain mechanism. Multivariate single-cell analysis is a starting point for identifying relationships among drug effects at a systems level and a step toward phenotypic profiling at the single-cell level. Our methods will be useful for discovering the mechanism and predicting the toxicity of new drugs.
Perlman
Zachary E
ZE
Institute of Chemistry and Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Slack
Michael D
MD
Feng
Yan
Y
Mitchison
Timothy J
TJ
Wu
Lani F
LF
Altschuler
Steven J
SJ
D001331:Automation; D002453:Cell Cycle / Q000187:drug effects; D016000:Cluster Analysis; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005456:Fluorescent Dyes; D006367:HeLa Cells; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008856:Microscopy, Fluorescence; D010600:Pharmacology / Q000379:methods*; D010641:Phenotype; D013223:Statistics as Topic; D018675:Toxicity Tests / Q000379:methods*
D005456:Fluorescent Dyes; D004247:DNA