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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We want to thank Leigh Anderson for sharing his insights on the economics and healthcare impact of in vitro diagnostics, Francesco Dati and Neil Greenberg for their input and advice on validation and clinical assay development, and Todd Golub and Eric Lander for their continuing support and encouragement to S.A.C. and M.A.G. S.A.C also thanks the many members of his laboratory who have contributed to developing and applying the conceptual framework for protein biomarker discovery and verification, including Jake Jaffe, Terri Addona, Karl Clauser, Shao-En Ong, Betty Chang, Eric Kuhn, Veronica Saenz-Vash, Hasmik Keshishian and Mike Burgess. This work was supported in part by grants to S.A.C. from the Women's Cancer Research Fund of the Entertainment Industry Foundation, the Bill and Melinda Gates Foundation and the National Institutes of Health, National Heart, Lung, and Blood Institute, and to M.A.G. from the National Institutes of Health, National Cancer Institute.
The authors declare no competing financial interests.
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Rifai, N., Gillette, M. & Carr, S. Protein biomarker discovery and validation: the long and uncertain path to clinical utility. Nat Biotechnol 24, 971–983 (2006). https://doi.org/10.1038/nbt1235
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