title: Clinical translation of MS-based, quantitative plasma proteomics: status, challenges, requirements, and potential.
abstract: Aided by the advent of advanced mass spectrometry (MS)-based technologies and methodologies, quantitative proteomics has emerged as a viable technique to capture meaningful data for candidate biomarker evaluation. To aid clinical translation, these methods generally utilize a bottom-up strategy with isotopically labeled standards and a targeted form of MS measurement.
  
  
  
  This article reviews the status, challenges, requirements, and potential of translating current, MS-based methods to the clinical laboratory. The described methods are discussed and contrasted within a fit-for-purpose approach, while different resources for quality control, quantitative analysis, and data interpretation are additionally provided. Expert commentary: Although great strides have been made over the past five years in developing reliable quantitative assays for plasma protein biomarkers, it is crucial for investigators to have an understanding of the clinical validation process, a major roadblock in translational research. Continued progress in method design and validation of protein assays is necessary to ultimately achieve widespread adoption and regulatory approval.
authors.affiliation: a Department of Applications Development , Cambridge Isotope Laboratories, Inc ., Tewksbury , MA , USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Percy
authors.affiliation: b Department of Surgery, Faculty of Medicine and Dentistry , University of Alberta , Edmonton , AB , Canada.
authors.forename: Simon
authors.initials: S
authors.lastname: Byrns
authors.affiliation: c Department of Pathology, School of Medicine, UCD Conway Institute , University College Dublin , Dublin 4 , Ireland.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Pennington
authors.affiliation: d Department of Pathology and Laboratory Medicine , St. Paul's Hospital , Vancouver , BC , Canada.|e Department of Pathology and Laboratory Medicine , University of British Columbia , Vancouver , Canada.
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Holmes
authors.affiliation: f Department of Clinical Biomarkers , SISCAPA Assay Technologies, Inc ., Washington , DC , USA.
authors.forename: N Leigh
authors.initials: NL
authors.lastname: Anderson
authors.affiliation: a Department of Applications Development , Cambridge Isotope Laboratories, Inc ., Tewksbury , MA , USA.
authors.forename: Tasha M
authors.initials: TM
authors.lastname: Agreste
authors.affiliation: a Department of Applications Development , Cambridge Isotope Laboratories, Inc ., Tewksbury , MA , USA.
authors.forename: Maureen A
authors.initials: MA
authors.lastname: Duffy
mesh_terms: D015415:Biomarkers / Q000097:blood*; D001798:Blood Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D013058:Mass Spectrometry; D040901:Proteomics
chemical_list: D015415:Biomarkers; D001798:Blood Proteins
keywords: Biomarker; MRM; MS; PRM; clinic; disease; protein; proteomics; quantification; translation