Integrated, high-throughput, multiomics platform enables data-driven construction of cellular responses and reveals global drug mechanisms of action
Jeremy L. Norris (VanderBilt University)
Melissa A. Farrow (VanderBilt University)
Danielle B. Gutierrez (VanderBilt University)
Lauren D. Palmer (VanderBilt University)
Nicole Muszynski (VanderBilt University)
Stacy D. Sherrod (VanderBilt University)
James C. Pino (VanderBilt University)
Jamie L. Allen (VanderBilt University)
Jeffrey M. Spraggins (VanderBilt University)
Alex L.R. Lubbock (VanderBilt University)
Ashley Jordan (VanderBilt University)
William Burns (VanderBilt University)
James C. Poland (VanderBilt University)
Carrie Romer (VanderBilt University)
M. Lisa Manier (VanderBilt University)
Yuan Wei Nei (VanderBilt University)
Boone M. Prentice (VanderBilt University)
Kristie L. Rose (VanderBilt University)
Salisha Hill (VanderBilt University)
Raf Van De Plas (VanderBilt University, TU Delft - Team Raf Van de Plas)
Tina Tsui (VanderBilt University)
Nathaniel M. Braman (VanderBilt University)
M. Ray Keller (VanderBilt University)
Stacey A. Rutherford (VanderBilt University)
Nichole Lobdell (VanderBilt University)
Carlos F. Lopez (VanderBilt University)
D. Borden Lacy (VanderBilt University)
John A. McLean (VanderBilt University)
John P. Wikswo (VanderBilt University)
Eric P. Skaar (VanderBilt University)
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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.
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