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J Proteome Res. 2017 Mar 3;16(3):1364-1375. doi: 10.1021/acs.jproteome.6b01004. Epub 2017 Feb 9.

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

Author information

1
Vanderbilt Institute of Chemical Biology, Vanderbilt University , Nashville, Tennessee 37232, United States.
2
Delft Center for Systems and Control, Delft University of Technology , Delft 2628 CD, The Netherlands.
3
Biomedical Engineering, Vanderbilt University School of Engineering , Nashville, Tennessee 37235, United States.

Abstract

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.

KEYWORDS:

cisplatin; drug discovery; high-throughput; mechanism of action; omics

PMID:
28088864
DOI:
10.1021/acs.jproteome.6b01004
[Indexed for MEDLINE]

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