Compound Classification Using Image‐Based Cellular Phenotypes
Abstract
Compounds with similar target specificities and modes of inhibition cause similar cellular phenotypes. Based on this observation, we hypothesized that we could quantitatively classify compounds with diverse mechanisms of action using cellular phenotypes and identify compounds with unintended cellular activities within a chemical series. We have developed Cytometrix technologies, a highly automated image-based system capable of quantifying, clustering, and classifying changes in cellular phenotypes for this purpose. Using this system, 45 out of 51 known compounds were accurately classified into 12 distinct mechanisms of action. We also demonstrate microtubule-binding activity in one of seven related cytochalasin actin poisons. This technology can be used for a variety of drug discovery applications, including high-throughput primary screening of chemical and siRNA libraries and as a secondary assay to detect unintended activities and toxicities.
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Feature reduction can be done either by removing redundant features or by using dimensional reduction methods such as principal components analysis (PCA).
“This can be done either by removing redundant features or using dimensional reduction methods such as principal components analysis (PCA)13.”
From A statistical framework for high-content phenotypic profiling using cellular feature distributions (2022) · cites this paper as [13]
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- Authors
- Adams, C. L., Kutsyy, V., Coleman, D. A., Cong, G., Crompton, A. M., Elias, K. A., Oestreicher, D. R., Trautman, J. K., & Vaisberg, E.
- Affiliations
- Cytokinetics (United States) (US)
- Venue
- Methods in Enzymology
- Publisher
- Elsevier
- Published
- 2006
- Volume
- 414
- Pages
- 440-468
- ISSN
- 0076-6879 (ISSN-L)
- OpenAlex
- W1522234506
- Cited by
- 51
- References
- 35
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 4 · 2022: 4 · 2021: 1 · 2020: 1 · 2019: 4 · 2018: 2 · 2017: 4 · 2016: 4 · 2015: 2 · 2014: 3 · 2013: 3 · 2012: 1
- FWCI
- 2.68
- Type
- book chapter
- Language
- en
- Open access
- closed
- Locations
- Methods in enzymology on CD-ROM/Methods in enzymology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Cell Image Analysis Techniques
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Keywords
- compound classification, cell phenotype, mechanism of action, microtubule binding, cytochalasin, high-throughput screening, siRNA library
- MeSH terms
- Actins, Animals, Cells, Cultured, Cytochalasins, Cytological Techniques, Endothelium, Vascular, Humans, Image Processing, Computer-Assisted, Immunohistochemistry, Microscopy, Fluorescence, Phenotype, Combinatorial Chemistry Techniques, RNA, Small Interfering, Cell Line, Tumor, Cell Size
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