Multiplex Cytological Profiling Assay to Measure Diverse Cellular States

作者: Sigrun M. Gustafsdottir , Vebjorn Ljosa , Katherine L. Sokolnicki , J. Anthony Wilson , Deepika Walpita

DOI: 10.1371/JOURNAL.PONE.0080999

关键词: Cell stainingMultiplexFluorescence-lifetime imaging microscopyBiologyExtramuralProfiling (information science)Computational biologyMolecular biologyNuclear stainingGeneral Biochemistry, Genetics and Molecular BiologyGeneral Agricultural and Biological SciencesGeneral Medicine

摘要: Computational methods for image-based profiling are under active development, but their success hinges on assays that can capture a wide range of phenotypes. We have developed multiplex cytological assay “paints the cell” with as many fluorescent markers possible without compromising our ability to extract rich, quantitative profiles in high throughput. The detects seven major cellular components. In pilot screen bioactive compounds, detected phenotypes and it clustered compounds similar annotated protein targets or chemical structure based profiles. results demonstrate captures subtle patterns combination morphological labels, thereby detecting effects even though not stained directly. This provides an unbiased approach characterize compound- disease-associated cell states support future probe discovery.

参考文章(25)
Cynthia L. Adams, Vadim Kutsyy, Daniel A. Coleman, Ge Cong, Anne Moon Crompton, Kathleen A. Elias, Donald R. Oestreicher, Jay K. Trautman, Eugeni Vaisberg, Compound classification using image-based cellular phenotypes. Methods in Enzymology. ,vol. 414, pp. 440- 468 ,(2006) , 10.1016/S0076-6879(06)14024-0
Gene Ontology Consortium, None, The Gene Ontology (GO) database and informatics resource Nucleic Acids Research. ,vol. 32, pp. 258D- 261 ,(2004) , 10.1093/NAR/GKH036
David C. Allison, Ross C. Donehower, Eric K. Rowinsky, John R. Roberts, Development of polyploidization in taxol-resistant human leukemia cells in vitro. Cancer Research. ,vol. 50, pp. 710- 716 ,(1990)
Masahiro Tanaka, Raynard Bateman, Daniel Rauh, Eugeni Vaisberg, Shyam Ramachandani, Chao Zhang, Kirk C Hansen, Alma L Burlingame, Jay K Trautman, Kevan M Shokat, Cynthia L Adams, An unbiased cell morphology-based screen for new, biologically active small molecules. PLOS Biology. ,vol. 3, pp. 128- 128 ,(2005) , 10.1371/JOURNAL.PBIO.0030128
Fuhai Li, Zheng Yin, Guangxu Jin, Hong Zhao, Stephen T. C. Wong, Chapter 17: Bioimage Informatics for Systems Pharmacology PLoS Computational Biology. ,vol. 9, pp. e1003043- ,(2013) , 10.1371/JOURNAL.PCBI.1003043
Zachary E Perlman, Michael D Slack, Yan Feng, Timothy J Mitchison, Lani F Wu, Steven J Altschuler, Multidimensional drug profiling by automated microscopy. Science. ,vol. 306, pp. 1194- 1198 ,(2004) , 10.1126/SCIENCE.1100709
Daniel W Young, Andreas Bender, Jonathan Hoyt, Elizabeth McWhinnie, Gung-Wei Chirn, Charles Y Tao, John A Tallarico, Mark Labow, Jeremy L Jenkins, Timothy J Mitchison, Yan Feng, Integrating high-content screening and ligand-target prediction to identify mechanism of action Nature Chemical Biology. ,vol. 4, pp. 59- 68 ,(2008) , 10.1038/NCHEMBIO.2007.53
François Marceau, Marie-Thérèse Bawolak, Robert Lodge, Johanne Bouthillier, Angélique Gagné-Henley, René C.-Gaudreault, Guillaume Morissette, Cation trapping by cellular acidic compartments: beyond the concept of lysosomotropic drugs. Toxicology and Applied Pharmacology. ,vol. 259, pp. 1- 12 ,(2012) , 10.1016/J.TAAP.2011.12.004
Paula M. Petrone, Benjamin Simms, Florian Nigsch, Eugen Lounkine, Peter Kutchukian, Allen Cornett, Zhan Deng, John W. Davies, Jeremy L. Jenkins, Meir Glick, Rethinking Molecular Similarity: Comparing Compounds on the Basis of Biological Activity ACS Chemical Biology. ,vol. 7, pp. 1399- 1409 ,(2012) , 10.1021/CB3001028