Norris Jeremy L, Farrow Melissa A, Gutierrez Danielle B, Palmer Lauren D, Muszynski Nicole, Sherrod Stacy D, Pino James C, Allen Jamie L, Spraggins Jeffrey M, Lubbock Alex L R, Jordan Ashley, Burns William, Poland James C, Romer Carrie, Manier M Lisa, Nei Yuan-Wei, Prentice Boone M, Rose Kristie L, Hill Salisha, Van de Plas Raf, Tsui Tina, Braman Nathaniel M, Keller M Ray, Rutherford Stacey A, Lobdell Nichole, Lopez Carlos F, Lacy D Borden, McLean John A, Wikswo John P, Skaar Eric P, Caprioli Richard M
Vanderbilt Institute of Chemical Biology, Vanderbilt University , Nashville, Tennessee 37232, United States.
Delft Center for Systems and Control, Delft University of Technology , Delft 2628 CD, The Netherlands.
J Proteome Res. 2017 Mar 3;16(3):1364-1375. doi: 10.1021/acs.jproteome.6b01004. Epub 2017 Feb 9.
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.
了解细胞如何对扰动做出反应对于生物学应用至关重要；然而，大多数分析细胞反应的方法在范围上仅限于预先确定的靶点。对分子机制的全局分析将推动我们对构成细胞扰动的复杂网络的理解，并在传染病发病机制、发育生物学、病理生理学、药理学和毒理学等领域取得进展。我们开发了一个高通量多组学平台，用于对细胞作用机制进行全面的、从头开始的表征。使用顺铂作为测试化合物进行的平台验证表明，在不到30天的时间内可以量化超过10000种独特的、显著的分子变化。这些数据很好地涵盖了已知的顺铂诱导的分子变化，并提供了对顺铂耐药性以前未被认识的见解。这项原理验证研究证明了该平台作为一种以高通量方式理解复杂细胞反应的资源的价值。
