Cited by 1,867Advanced Proteomics Techniques and ApplicationsAdvanced Biosensing Techniques and ApplicationsBiomarkers in Disease Mechanisms

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Protein biomarker discovery and validation: the long and uncertain path to clinical utility

Rifai, Nader, Gillette, Michael A, Carr, Steven A·2006·Nature Biotechnology

DOI 10.1038/nbt1235

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Abstract

Better biomarkers are urgently needed to improve diagnosis, guide molecularly targeted therapy and monitor activity and therapeutic response across a wide spectrum of disease. Proteomics methods based on mass spectrometry hold special promise for the discovery of novel biomarkers that might form the foundation for new clinical blood tests, but to date their contribution to the diagnostic armamentarium has been disappointing. This is due in part to the lack of a coherent pipeline connecting marker discovery with well-established methods for validation. Advances in methods and technology now enable construction of a comprehensive biomarker pipeline from six essential process components: candidate discovery, qualification, verification, research assay optimization, biomarker validation and commercialization. Better understanding of the overall process of biomarker discovery and validation and of the challenges and strategies inherent in each phase should improve experimental study design, in turn increasing the efficiency of biomarker development and facilitating the delivery and deployment of novel clinical tests.

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Authors: Rifai, N., Gillette, M. A., & Carr, S. A.
Affiliations: Boston Children's Hospital (US)
Broad Institute (US)
Corresponding author: Carr, Steven A
ORCID: Rifai, Nader
Gillette, Michael A
Carr, Steven A
Venue: Nature Biotechnology
Publisher: Springer Science and Business Media LLC
Published: 2006-08
Volume: 24
Issue: 8
Pages: 971-983
ISSN: 0733-222X (ISSN-L)
1087-0156
1546-1696
DOI: 10.1038/nbt1235
OpenAlex: W2094229819
Cited by: 1,867
References: 118
Citations by year: 2026: 56 · 2025: 70 · 2024: 75 · 2023: 66 · 2022: 69 · 2021: 85 · 2020: 74 · 2019: 88 · 2018: 91 · 2017: 96 · 2016: 99 · 2015: 130 · 2014: 131 · 2013: 116 · 2012: 138
FWCI: 7.25
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Biotechnology (publishedVersion)
PubMed (publishedVersion)
Topics: Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Advanced Biosensing Techniques and Applications
Life Sciences › Immunology and Microbiology › Immunology › Biomarkers in Disease Mechanisms
Keywords: protein biomarkers, biomarker discovery, biomarker validation, mass spectrometry-based proteomics, diagnostic biomarkers, biomarker qualification, research design
MeSH terms: Animals, Blood Chemical Analysis, Blood Proteins, Humans, Peptide Mapping, Sensitivity and Specificity, Mass Spectrometry, Biomarkers, Protein Array Analysis

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Protein biomarker discovery and validation: the long and uncertain path to clinical utility

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