Mass Spectrometry-Based Approaches for Targeted Quantitative Proteomics in Biomarker Development
Date of Completion
proteomics, mass spectrometry, biomarker, derivatization
Dr. Xudong Yao
Dr. Christian Brueckner
Dr. Alfredo Angeles-Boza
Dr. Jie He
Dr. Fatma Selampinar
Field of Study
Doctor of Philosophy
The development of disease protein biomarkers and their use in clinical research have great applications in the diagnosis, prognosis, and treatment of complex diseases. Mass spectrometry methods for protein biomarker quantitation have recently gained importance in the early stages of the biomarker pipeline, but their application in the validation phase is limited by their low sample throughput. The technology of ultrathroughput mass spectrometry (uMS) transforms the intrinsic quantitation capability of MS analyte multiplexing to sample multiplexing. Herein, the novel MS-based bioanalytical platform utilized decoupled use of isotopic quantitation reference standard and non-isotopic mass coding reagents to enable one-experiment quantitation of a target protein biomarker candidate in multiple non-depleted serum samples. Screened repository of signal-enhancing peptidyl reagents enabled N-in-1 analyses for a cost-effective, high sample throughput strategy for protein biomarker validation applications. The signal enhancement and sample multiplexing capability of the derivatization technique were then further investigated within proteomic profiling and derived towards a global quantitative approach.
Castillo, Mary Joan, "Mass Spectrometry-Based Approaches for Targeted Quantitative Proteomics in Biomarker Development" (2015). Doctoral Dissertations. 990.