Integrated, high-throughput, multiomics platform enables data-driven construction of cellular responses and reveals global drug mechanisms of action

Jeremy L. Norris, Melissa A. Farrow, Danielle B. Gutierrez, Lauren D. Palmer, Nicole Muszynski, Stacy D. Sherrod, James C. Pino, Jamie L. Allen, Jeffrey M. Spraggins, Alex L.R. Lubbock, Ashley Jordan, William Burns, James C. Poland, Carrie Romer, M. Lisa Manier, Yuan Wei Nei, Boone M. Prentice, Kristie L. Rose, Salisha Hill, Raf Van De PlasTina Tsui, Nathaniel M. Braman, M. Ray Keller, Stacey A. Rutherford, Nichole Lobdell, Carlos F. Lopez, D. Borden Lacy, John A. McLean, John P. Wikswo, Eric P. Skaar

Research output: Contribution to journalArticleScientificpeer-review

13 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1364-1375
JournalJournal of Proteome Research
Volume16
Issue number3
DOIs
Publication statusPublished - 2017

Keywords

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

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    Norris, J. L., Farrow, M. A., Gutierrez, D. B., Palmer, L. D., Muszynski, N., Sherrod, S. D., Pino, J. C., Allen, J. L., Spraggins, J. M., Lubbock, A. L. R., Jordan, A., Burns, W., Poland, J. C., Romer, C., Manier, M. L., Nei, Y. W., Prentice, B. M., Rose, K. L., Hill, S., ... Skaar, E. P. (2017). Integrated, high-throughput, multiomics platform enables data-driven construction of cellular responses and reveals global drug mechanisms of action. Journal of Proteome Research, 16(3), 1364-1375. https://doi.org/10.1021/acs.jproteome.6b01004