title: Integrated, High-Throughput, Multiomics Platform Enables Data-Driven Construction of Cellular Responses and Reveals Global Drug Mechanisms of Action.
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.
authors.forename: Jeremy L
authors.identifier: 0000-0003-1725-8406
authors.initials: JL
authors.lastname: Norris
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Farrow
authors.forename: Danielle B
authors.identifier: 0000-0001-6355-2134
authors.initials: DB
authors.lastname: Gutierrez
authors.forename: Lauren D
authors.initials: LD
authors.lastname: Palmer
authors.forename: Nicole
authors.initials: N
authors.lastname: Muszynski
authors.affiliation: Vanderbilt Institute of Chemical Biology, Vanderbilt University , Nashville, Tennessee 37232, United States.
authors.forename: Stacy D
authors.initials: SD
authors.lastname: Sherrod
authors.forename: James C
authors.initials: JC
authors.lastname: Pino
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Allen
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Spraggins
authors.forename: Alex L R
authors.initials: AL
authors.lastname: Lubbock
authors.forename: Ashley
authors.initials: A
authors.lastname: Jordan
authors.forename: William
authors.initials: W
authors.lastname: Burns
authors.affiliation: Vanderbilt Institute of Chemical Biology, Vanderbilt University , Nashville, Tennessee 37232, United States.
authors.forename: James C
authors.initials: JC
authors.lastname: Poland
authors.forename: Carrie
authors.initials: C
authors.lastname: Romer
authors.forename: M Lisa
authors.initials: ML
authors.lastname: Manier
authors.forename: Yuan-Wei
authors.initials: YW
authors.lastname: Nei
authors.forename: Boone M
authors.initials: BM
authors.lastname: Prentice
authors.forename: Kristie L
authors.initials: KL
authors.lastname: Rose
authors.forename: Salisha
authors.initials: S
authors.lastname: Hill
authors.affiliation: Delft Center for Systems and Control, Delft University of Technology , Delft 2628 CD, The Netherlands.
authors.forename: Raf
authors.initials: R
authors.lastname: Van de Plas
authors.forename: Tina
authors.initials: T
authors.lastname: Tsui
authors.affiliation: Biomedical Engineering, Vanderbilt University School of Engineering , Nashville, Tennessee 37235, United States.
authors.forename: Nathaniel M
authors.initials: NM
authors.lastname: Braman
authors.affiliation: Vanderbilt Institute of Chemical Biology, Vanderbilt University , Nashville, Tennessee 37232, United States.
authors.forename: M Ray
authors.initials: MR
authors.lastname: Keller
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Rutherford
authors.forename: Nichole
authors.initials: N
authors.lastname: Lobdell
authors.affiliation: Biomedical Engineering, Vanderbilt University School of Engineering , Nashville, Tennessee 37235, United States.
authors.forename: Carlos F
authors.identifier: 0000-0003-3668-7468
authors.initials: CF
authors.lastname: Lopez
authors.forename: D Borden
authors.initials: DB
authors.lastname: Lacy
authors.affiliation: Vanderbilt Institute of Chemical Biology, Vanderbilt University , Nashville, Tennessee 37232, United States.
authors.forename: John A
authors.identifier: 0000-0001-8918-6419
authors.initials: JA
authors.lastname: McLean
authors.affiliation: Biomedical Engineering, Vanderbilt University School of Engineering , Nashville, Tennessee 37235, United States.
authors.forename: John P
authors.identifier: 0000-0003-2790-1530
authors.initials: JP
authors.lastname: Wikswo
authors.forename: Eric P
authors.initials: EP
authors.lastname: Skaar
authors.forename: Richard M
authors.initials: RM
authors.lastname: Caprioli
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D002470:Cell Survival; D002477:Cells / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology; D019295:Computational Biology / Q000379:methods; D057166:High-Throughput Screening Assays / Q000379:methods*; D006801:Humans; D053858:Metabolic Networks and Pathways
chemical_list: D002945:Cisplatin
keywords: cisplatin; drug discovery; high-throughput; mechanism of action; omics