Integrated, High-Throughput, Multiomics Platform Enables Data-Driven Construction of Cellular Responses and Reveals Global Drug Mechanisms of Action

An understanding of how cells respond to perturbation is essential for biological applications; however, most approaches for profiling cellular response are limited in scope to pre-established targets. Global analysis of molecular mechanism will advance our understanding of the complex networks cons...

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Bibliographic Details
Published in:	Journal of proteome research Vol. 16; no. 3; pp. 1364 - 1375
Main Authors:	Norris, Jeremy L, Farrow, Melissa A, Gutierrez, Danielle B, Palmer, Lauren D, Muszynski, Nicole, Sherrod, Stacy D, Pino, James C, Allen, Jamie L, Spraggins, Jeffrey M, Lubbock, Alex L. R, Jordan, Ashley, Burns, William, Poland, James C, Romer, Carrie, Manier, M. Lisa, Nei, Yuan-wei, Prentice, Boone M, Rose, Kristie L, Hill, Salisha, Van de Plas, Raf, Tsui, Tina, Braman, Nathaniel M, Keller, M. Ray, Rutherford, Stacey A, Lobdell, Nichole, Lopez, Carlos F, Lacy, D. Borden, McLean, John A, Wikswo, John P, Skaar, Eric P, Caprioli, Richard M
Format:	Journal Article
Language:	English
Published:	United States American Chemical Society 03-03-2017
Subjects:	Apoptosis Cell Line Cell Survival Cells - drug effects Cisplatin - pharmacology Computational Biology - methods High-Throughput Screening Assays - methods Humans Metabolic Networks and Pathways mechanism of action drug discovery omics cisplatin high-throughput
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Summary:	An understanding of how cells respond to perturbation is essential for biological applications; however, most approaches for profiling cellular response are limited in scope to pre-established targets. Global analysis of molecular mechanism will advance our understanding of the complex networks constituting cellular perturbation and lead to advancements in areas, such as infectious disease pathogenesis, developmental biology, pathophysiology, pharmacology, and toxicology. We have developed a high-throughput multiomics platform for comprehensive, de novo characterization of cellular mechanisms of action. Platform validation using cisplatin as a test compound demonstrates quantification of over 10 000 unique, significant molecular changes in less than 30 days. These data provide excellent coverage of known cisplatin-induced molecular changes and previously unrecognized insights into cisplatin resistance. This proof-of-principle study demonstrates the value of this platform as a resource to understand complex cellular responses in a high-throughput manner.
ISSN:	1535-3893 1535-3907
DOI:	10.1021/acs.jproteome.6b01004