Mass spectrometry-based approach for protein biomarker verification

The search for protein biomarkers has been a highly pursued topic in the proteomics community over the last decade. This relentless search is due to the constant need for validated biomarkers that could facilitate disease risk stratification, disease diagnosis, disease prognosis, and disease monitoring as well as drug development, which ultimately would improve our quality of life. The recent development of proteomic technologies, including the advancement of mass spectrometers with high sensitivity and speed, has greatly advanced the discovery of potential biomarkers. Before these potential biomarkers can be developed into valid assays to be used in clinic, one of the bottlenecks lies in the development of well-established high-throughput verification assays to screen the many biomarker candidates identified in the discovery stage to prioritize the handful that are not only valid but also specific and sensitive enough to enter into the validation stage. Recently, the mass spectrometry–based approach using multiple-reaction monitoring mass spectrometry (MRM-MS) in combination with isotope-labeled internal standards has been extensively investigated as a tool for high-throughput protein biomarker verification purpose. In this chapter, we provide an update on recent developments and applications of the mass spectrometry–based approaches toward biomarker verification efforts as well as discussions on their current limitations.

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