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

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.