Multidimensional Drug Profiling By Automated Microscopy

TLDR

Multivariate single‑cell analysis provides a foundation for uncovering relationships among drug effects at a systems level and advancing phenotypic profiling at the single‑cell level. The study presents a high‑throughput cytological profiling method by microscopy aimed at discovering drug mechanisms and predicting toxicity. The system quantitatively measures multidimensional cell states across perturbations and profiles dose‑dependent drug phenotypes using a titration‑invariant similarity score (TISS). This method successfully categorized blinded drugs and suggested targets for drugs of uncertain mechanism.

Abstract

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.