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

AUTHORS

Norris JLJeremy L , Farrow MAMelissa A , Gutierrez DBDanielle B , Palmer LDLauren D , Muszynski NNicole , Sherrod SDStacy D , Pino JCJames C , Allen JLJamie L , Spraggins JMJeffrey M , Lubbock ALAlex L R , Jordan AAshley , Burns WWilliam , Poland JCJames C , Romer CCarrie , Manier MLM Lisa , Nei YWYuan-Wei , Prentice BMBoone M , Rose KLKristie L , Hill SSalisha , Van de Plas RRaf , Tsui TTina , Braman NMNathaniel M , Keller MRM Ray , Rutherford SAStacey A , Lobdell NNichole , Lopez CFCarlos F , Lacy DBD Borden , McLean JAJohn A , Wikswo JPJohn P , Skaar EPEric P , Caprioli RMRichard M . Journal of proteome research. 2017 2 9; 16(3). 1364-1375

PMID: 28088864[PubMed].

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.