Mass spectrometry based biomarker discovery, verification, and validation--quality assurance and control of protein biomarker assays.
In its early years, mass spectrometry (MS)-based proteomics focused on the cataloging of proteins found in different species or different tissues. By 2005, proteomics was being used for protein quantitation, typically based on "proteotypic" peptides which act as surrogates for the parent proteins. Biomarker discovery is usually done by non-targeted "shotgun" proteomics, using relative quantitation methods to determine protein expression changes that correlate with disease (output given as "up-or-down regulation" or "fold-increases"). MS-based techniques can also perform "absolute" quantitation which is required for clinical applications (output given as protein concentrations). Here we describe the differences between these methods, factors that affect the precision and accuracy of the results, and some examples of recent studies using MS-based proteomics to verify cancer-related biomarkers.
University of Victoria - Genome British Columbia Proteomics Centre, Vancouver Island Technology Park, #3101 - 4464 Markham St., Victoria, BC V8Z 7X8, Canada.
Carol E
CE
Parker
University of Victoria - Genome British Columbia Proteomics Centre, Vancouver Island Technology Park, #3101 - 4464 Markham St., Victoria, BC V8Z 7X8, Canada; Department of Biochemistry and Microbiology, University of Victoria, Petch Building Room 207, 3800 Finnerty Rd., Victoria, BC V8P 5C2, Canada. Electronic address: christoph@proteincentre.com.
Christoph H
CH
Borchers
D014408:Biomarkers, Tumor / Q000302:isolation & purification* / Q000378:metabolism; D056726:Genetic Association Studies / Q000379:methods* / Q000592:standards; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods* / Q000592:standards; D009363:Neoplasm Proteins / Q000302:isolation & purification* / Q000378:metabolism; D040901:Proteomics / Q000379:methods / Q000592:standards; D011786:Quality Control; D054928:Validation Studies as Topic
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins
Biomarker discovery; Biomarkers; Cancer; Mass spectrometry; Multiple reaction monitoring; Plasma or serum; Selected reaction monitoring; Targeted proteomics; Validation; Verification