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Mol Biol Cell DOI:10.1091/mbc.E20-12-0784

Predicting cell health phenotypes using image-based morphology profiling.

Publication TypeJournal Article
Year of Publication2021
AuthorsWay, GP, Kost-Alimova, M, Shibue, T, Harrington, WF, Gill, S, Piccioni, F, Becker, T, Shafqat-Abbasi, H, Hahn, WC, Carpenter, AE, Vazquez, F, Singh, S
JournalMol Biol Cell
Volume32
Issue9
Pages995-1005
Date Published2021 04 19
ISSN1939-4586
KeywordsAlgorithms, Biological Assay, Cell Line, Cells, Forecasting, Humans, Image Processing, Computer-Assisted, Machine Learning, Microscopy, Phenotype
Abstract

Genetic and chemical perturbations impact diverse cellular phenotypes, including multiple indicators of cell health. These readouts reveal toxicity and antitumorigenic effects relevant to drug discovery and personalized medicine. We developed two customized microscopy assays, one using four targeted reagents and the other three targeted reagents, to collectively measure 70 specific cell health phenotypes including proliferation, apoptosis, reactive oxygen species, DNA damage, and cell cycle stage. We then tested an approach to predict multiple cell health phenotypes using Cell Painting, an inexpensive and scalable image-based morphology assay. In matched CRISPR perturbations of three cancer cell lines, we collected both Cell Painting and cell health data. We found that simple machine learning algorithms can predict many cell health readouts directly from Cell Painting images, at less than half the cost. We hypothesized that these models can be applied to accurately predict cell health assay outcomes for any future or existing Cell Painting dataset. For Cell Painting images from a set of 1500+ compound perturbations across multiple doses, we validated predictions by orthogonal assay readouts. We provide a web app to browse predictions: http://broad.io/cell-health-app. Our approach can be used to add cell health annotations to Cell Painting datasets.

DOI10.1091/mbc.E20-12-0784
Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/33534641?dopt=Abstract

Alternate JournalMol Biol Cell
PubMed ID33534641
PubMed Central IDPMC8108524
Grant ListR35 GM122547 / GM / NIGMS NIH HHS / United States
U01 CA176058 / CA / NCI NIH HHS / United States