Multidimensional drug profiling by automated microscopy

被引:501
作者
Perlman, ZE
Slack, MD
Feng, Y
Mitchison, TJ
Wu, LF [1 ]
Altschuler, SJ
机构
[1] Harvard Univ, Bauer Ctr Gen Res, Cambridge, MA 02138 USA
[2] Harvard Univ, Sch Med, Inst Chem & Cell Biol, Boston, MA 02115 USA
[3] Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA
关键词
D O I
10.1126/science.1100709
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 profiting at the single-cell level. Our methods will be useful for discovering the mechanism and predicting the toxicity of new drugs.
引用
收藏
页码:1194 / 1198
页数:5
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