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

The DOI matches its Crossref record; 116 of the 118 references it cites were found in a registry or an index.

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

Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1038/nbt1235

Cites

116 of 116 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT
Martin Bland, J., & Altman, D. (1986) · The Lancet · doi:10.1016/s0140-6736(86)90837-8 · Cited by 47,965
Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II)
Grundy, S. M., Bilheimer, D. W., Chait, A., Clark, L. T., Denke, M. A., Havel, R. J., Hazzard, W. R., Hulley, S. B., Hunninghake, D. B., Kreisberg, R. A., et al. (1993) · JAMA · doi:10.1001/jama.269.23.3015 · Cited by 27,944
Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III)
Expert Panel on Detection, E. (2001) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.285.19.2486 · Cited by 26,011
Akufo and Ibarapa
Beckett, A. H., Rowland, M., & TURNER, P. (1965) · The Lancet · doi:10.1016/s0140-6736(65)91037-8 · Cited by 16,917
Practical Statistics for Medical Research.
Walter, S., & Altman, D. G. (1992) · Biometrics · doi:10.2307/2532320 · Cited by 11,666
Mass spectrometry-based proteomics
Aebersold, R., & Mann, M. (2003) · Nature · doi:10.1038/nature01511 · Cited by 6,955
Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine
ZWEIG, M. H., & Campbell, G. (1993) · Clinical Chemistry · doi:10.1093/clinchem/39.4.561 · Cited by 6,595
Practical Statistics for Medical Research.
Bartko, J. J., & Altman, D. G. (1992) · Journal of the American Statistical Association · doi:10.2307/2290246 · Cited by 4,834
The Human Plasma Proteome
Anderson, N. L., & Anderson, N. G. (2002) · Molecular & Cellular Proteomics · doi:10.1074/mcp.r200007-mcp200 · Cited by 4,414
Tissue microarrays for high-throughput molecular profiling of tumor specimens
Kononen, J., Bubendorf, L., Kallionimeni, A., Barlund, M. T., Schraml, P., Leighton, S. B., Torhorst, J. K. H., Mihatsch, M. J., Sauter, G., & Kallionimeni, O.-P. (1998) · Nature Medicine · doi:10.1038/nm0798-844 · Cited by 4,101

Flagged first, then by citations

Show all 118 references

2 of the 118 references couldn’t be matched to a known paper.

Research works printed but not linked: 2

Entertainment Industry Foundation, Women's Cancer Research Fund Breast Cancer Biomarker Discovery Project. http://www.eifoundation.org/national/wcrf/press/article2005-10-04.html .
International Standards Organization, I.O.F.S. Accuracy (Trueness and Precision) of Measurement Methods and Results (ISO 5725)-Part 1: General Principles and Definitions (ISO, Geneva, 1994).

Sorted by citations

Items 701–800 of 1,000

Optimized sample preparation of endoscopic collected pancreatic fluid for SDS‐PAGE analysis
Paulo, J. A., Lee, L., Wu, B. U., Repas, K. A., Banks, P. A., Conwell, D. L., & Steen, H. (2010) · Electrophoresis · doi:10.1002/elps.200900762 · Cited by 30
Biochemical Markers of In Vivo Hepatotoxicity
Arika, W. M., & Nyamai, D. W. (2016) · Journal of Clinical Toxicology · doi:10.4172/2161-0495.1000297 · Cited by 31
Temporal profiles of plasma proteome during childhood development
Liu, C., Bramer, L., Webb‐Robertson, B., Waugh, K., Rewers, M., & Zhang, Q. (2016) · Journal of Proteomics · doi:10.1016/j.jprot.2016.11.016 · Cited by 29
Barcode DNA-Mediated Signal Amplifying Strategy for Ultrasensitive Biomolecular Detection on Matrix-Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF) Mass Spectrometry
Ahmad, R., Jang, H., Batule, B. S., & Park, H. G. (2017) · Analytical Chemistry · doi:10.1021/acs.analchem.7b01535 · Cited by 30
Identification of Borrelia protein candidates in mouse skin for potential diagnosis of disseminated Lyme borreliosis
Grillon, A., Westermann, B., Cantero, P., Jaulhac, B., Voordouw, M. J., Kapps, D., Collin, E., Barthel, C., Ehret‐Sabatier, L., & Boulanger, N. (2017) · Scientific Reports · doi:10.1038/s41598-017-16749-9 · Cited by 30
Internal Standard Triggered-Parallel Reaction Monitoring Mass Spectrometry Enables Multiplexed Quantification of Candidate Biomarkers in Plasma
Kennedy, J. J., Whiteaker, J. R., Ivey, R. G., Burian, A., Chowdhury, S., Tsai, C., Liu, T., Lin, C., Murillo, O. D., Lundeen, R. A., et al. (2022) · Analytical Chemistry · doi:10.1021/acs.analchem.1c04382 · Cited by 31
Mass spectrometry-based proteomics and peptidomics for biomarker discovery in neurodegenerative diseases.
Wei, X. L., & Li, L. (2009) · PubMed Central · Cited by 30
Recent advances in biomarker discovery in solid organ transplant by proteomics
Sigdel, T. K., & Sarwal, M. (2011) · Expert Review of Proteomics · doi:10.1586/epr.11.66 · Cited by 30
Salivary Epigenetic Biomarkers in Head and Neck Squamous Cell Carcinomas
Lim, Y., Sun, C. X., Tran, P., & Punyadeera, C. (2016) · Biomarkers in Medicine · doi:10.2217/bmm.16.2 · Cited by 32
Two-Layer Architecture Using Atom Transfer Radical Polymerization for Enhanced Sensing and Detection in Complex Media
Brault, N. D., Sundaram, H. S., Huang, C., Li, Y., Yu, Q., & Jiang, S. (2012) · Biomacromolecules · doi:10.1021/bm301335r · Cited by 29
Glycoprotein Profiles of Human Breast Cells Demonstrate a Clear Clustering of Normal/Benign versus Malignant Cell Lines and Basal versus Luminal Cell Lines
Yen, T., Macher, B. A., McDonald, C. A., Alleyne-Chin, C., & Timpe, L. C. (2011) · Journal of Proteome Research · doi:10.1021/pr201041j · Cited by 29
Targeted Tissue Proteomic Analysis of Human Astrocytomas
Fang, X., Wang, C., Balgley, B. M., Zhao, K., Wang, W., He, F., Weil, R. J., & Lee, C. S. (2012) · Journal of Proteome Research · doi:10.1021/pr300303t · Cited by 29
Optimization of liquid chromatography–multiple reaction monitoring cubed mass spectrometry assay for protein quantification: Application to aquaporin-2 water channel in human urine
Jaffuel, A., Lemoine, J., Aubert, C., Simon, R., Léonard, J., Gautier, J., Pasquier, O., & Salvador, A. (2013) · Journal of Chromatography A · doi:10.1016/j.chroma.2013.05.068 · Cited by 29
A Quantitative Proteomic Approach to Prion Disease Biomarker Research: Delving into the Glycoproteome
Wei, X. L., Herbst, A. J., Ma, D., Aiken, J. M., & Li, L. (2011) · Journal of Proteome Research · doi:10.1021/pr2000495 · Cited by 29
Identification of Direct Target Engagement Biomarkers for Kinase-Targeted Therapeutics
Paweletz, C. P., Andersen, J. N., Pollock, R. M., Nagashima, K., Hayashi, M. L., Yu, S. U., Guo, H., Bobkova, E. V., Xu, Z., Northrup, A. B., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0026459 · Cited by 29
Quantitative Proteomics Analysis of Tissue Interstitial Fluid for Identification of Novel Serum Candidate Diagnostic Marker for Hepatocellular Carcinoma
Sun, W., Xing, B., Guo, L., Liu, Z., Mu, J., Sun, L., Wei, H., Zhao, X., Qian, X., Jiang, Y., et al. (2016) · Scientific Reports · doi:10.1038/srep26499 · Cited by 29
Quantification of biomarkers for beef meat qualities using a combination of Parallel Reaction Monitoring- and antibody-based proteomics
Bonnet, M., Soulat, J., Bons, J., Leger, S., de Koning, L., Carapito, C., & Picard, B. B. (2020) · Food Chemistry · doi:10.1016/j.foodchem.2020.126376 · Cited by 29
Precipitation-based colorimetric multiplex immunoassay in hydrogel particles
Roh, Y. H., Lee, H. J., Kim, J. Y., Kim, H. U., Kim, S. M., & Bong, K. W. (2020) · Lab on a Chip · doi:10.1039/d0lc00325e · Cited by 29
Development and Multiple Validation of the Protein Multi-marker Panel for Diagnosis of Pancreatic Cancer
Kim, Y., Yeo, I., Huh, I., Kim, J., Han, D., Jang, J., & Kim, Y. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-3929 · Cited by 28
SWATH Based Quantitative Proteomics Reveals Significant Lipid Metabolism in Early Myopic Guinea Pig Retina
Bian, J., Sze, Y. H., Tse, D. Y., To, C. H., McFadden, S. A., Lam, C. S. Y., Li, K. K., & Lam, T. C. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22094721 · Cited by 30
Diagnostic circulating biomarkers to detect vision‐threatening diabetic retinopathy: Potential screening tool of the future?
Frudd, K., Sivaprasad, S., Raman, R., Krishnakumar, S., Revathy, Y. R., & Turowski, P. (2021) · Acta Ophthalmologica · doi:10.1111/aos.14954 · Cited by 29
Spatial barcoding-enabled highly multiplexed immunoassay with digital microfluidics
Li, H., Liu, X., Zhu, F., Ma, D., Miao, C., Su, H., Deng, J., Ye, H., Dong, H., Bai, X., et al. (2022) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2022.114557 · Cited by 29
Miniaturized Microarray-Format Digital ELISA Enabled by Lithographic Protein Patterning
Stephens, A., Song, Y., McClellan, B. L., Su, S., Xu, S. H., Chen, K., Castro, M. G., Singer, B. H., & Kurabayashi, K. (2023) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2023.115536 · Cited by 29
Discovery of nutritional biomarkers: future directions based on omics technologies
Odriozola, L., & Corrales, F. J. (2015) · International Journal of Food Sciences and Nutrition · doi:10.3109/09637486.2015.1038224 · Cited by 30
Plasma proteomic analysis of stable coronary artery disease indicates impairment of reverse cholesterol pathway
Basak, T., Tanwar, V. S., Bhardwaj, G., Bhardwaj, N., Ahmad, S., Garg, G., Sreenivas, V., Karthikeyan, G., Seth, S., & Sengupta, S. (2016) · Scientific Reports · doi:10.1038/srep28042 · Cited by 29
Preparation of magnetic microspheres functionalized by lanthanide oxides for selective isolation of bovine hemoglobin
Wang, J., Tan, S., Liang, Q., Sun, S., Han, Q., & Ding, M. (2018) · Talanta · doi:10.1016/j.talanta.2018.07.059 · Cited by 29
Transcriptional and Proteomic Analysis Revealed a Synergistic Effect of Aflatoxin M1 and Ochratoxin A Mycotoxins on the Intestinal Epithelial Integrity of Differentiated Human Caco-2 Cells
Gao, Y., Li, S., Bao, X., Luo, C., Yang, H., Wang, J., Zhao, S., & Zheng, N. (2018) · Journal of Proteome Research · doi:10.1021/acs.jproteome.8b00241 · Cited by 29
Proteomics studies reveal important information on small molecule therapeutics: a case study on plasma proteins
Zolla, L. (2008) · Drug Discovery Today · doi:10.1016/j.drudis.2008.09.013 · Cited by 29
Comprehensive approaches to expanding CRISPR biosensor applications beyond nucleic acid targets
Nandi, I., Verma, J., Prasad, R., Singh, S. K., & Chandra, P. (2025) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2025.118179 · Cited by 28
Building from the “Ground” Up: Developing interfacial chemistry for solid-phase nucleic acid hybridization assays based on quantum dots and fluorescence resonance energy transfer
Noor, M. O., Petryayeva, E., Tavares, A. J., Uddayasankar, U., Algar, W. R., & Krull, U. J. (2013) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2013.08.010 · Cited by 28
Clinical proteomics and OMICS clues useful in translational medicine research
López‐Camacho, E., Madero, L., López-Pascual, J., & Latterich, M. (2012) · Proteome Science · doi:10.1186/1477-5956-10-35 · Cited by 28
Post-Genomics Nanotechnology Is Gaining Momentum: Nanoproteomics and Applications in Life Sciences
Kobeissy, F. H., Gülbakan, B., Alawieh, A. M., Karam, P., Zhang, Z., Guingab-Cagmat, J. D., Mondello, S., Tan, W., Anagli, J. Y., & Wang, K. (2014) · OMICS A Journal of Integrative Biology · doi:10.1089/omi.2013.0074 · Cited by 29
Array-Based Online Two Dimensional Liquid Chromatography System Applied to Effective Depletion of High-Abundance Proteins in Human Plasma
Huang, Z., Yan, G., Gao, M., & Zhang, X. (2016) · Analytical Chemistry · doi:10.1021/acs.analchem.5b04553 · Cited by 28
Biomarker discovery from the top down: Protein biomarkers for efficient virus transmission by insects (Homoptera: Aphididae) discovered by coupling genetics and 2‐D DIGE
Cilia, M., Howe, K. J., Fish, T. L., Smith, D., Mahoney, J. E., Tamborindeguy, C., Burd, J. D., Thannhauser, T. W., & Gray, S. M. (2011) · PROTEOMICS · doi:10.1002/pmic.201000519 · Cited by 27
Improved Ranking Functions for Protein and Modification-Site Identifications
Bern, M. W., & Goldberg, D. T. (2008) · Journal of Computational Biology · doi:10.1089/cmb.2007.0119 · Cited by 28
A Highly Automated Shotgun Proteomic Workflow: Clinical Scale and Robustness for Biomarker Discovery in Blood
Dayon, L., Galindo, A. N., Cominetti, O., Corthésy, J., & Kussmann, M. (2017) · Methods in molecular biology · doi:10.1007/978-1-4939-7057-5_30 · Cited by 28
Sex hormone‐binding globulin ( SHBG ) is a potential early diagnostic biomarker for gastric cancer
Cheng, C., Chang, C., Patria, Y. N., Chang, R.-T., Liu, Y., Li, F., Shih, H., & Lin, C. (2017) · Cancer Medicine · doi:10.1002/cam4.1254 · Cited by 27
Combined use of protein biomarkers and network analysis unveils deregulated regulatory circuits in Duchenne muscular dystrophy
Parolo, S., Marchetti, L., Lauria, M., Misselbeck, K., Scott‐Boyer, M., Caberlotto, L., & Priami, C. (2018) · PLoS ONE · doi:10.1371/journal.pone.0194225 · Cited by 30
Open: Mucosal-luminal interface proteomics reveals biomarkers of pediatric inflammatory bowel disease-associated colitis
Deeke, S. A., Starr, A. E., Ning, Z., Ahmadi, S., Zhang, X., Mayne, J., Chiang, C., Singleton, R., Benchimol, E. I., Mack, D. R., et al. (2018) · The American Journal of Gastroenterology · doi:10.1038/s41395-018-0024-9 · Cited by 28
Gut Microbiota and Postbiotic Metabolites: Biotic Intervention for Enhancing Vaccine Responses and Personalized Medicine for Disease Prevention
Mojgani, N., Ashique, S., Moradi, M., Bagheri, M., Garg, A., Kaushik, M., Hussain, M. S., Yasmin, S., & Ansari, M. Y. (2025) · Probiotics and Antimicrobial Proteins · doi:10.1007/s12602-025-10477-7 · Cited by 33
Cerebrospinal fluid markers of idiopathic intracranial hypertension: Is the renin-angiotensinogen system involved?
Brettschneider, J., Hartmann, N., Lehmensiek, V., Mogel, H., Ludolph, A. C., & Tumani, H. (2010) · Cephalalgia · doi:10.1177/0333102410375726 · Cited by 27
The discovery and validation of colorectal cancer biomarkers
Ang, C., Phung, J., & Nice, E. C. (2010) · Biomedical Chromatography · doi:10.1002/bmc.1528 · Cited by 27
Discovery and Targeted Proteomics on Cutaneous Biopsies Infected by Borrelia to Investigate Lyme Disease*
Schnell, G., Bœuf, A., Westermann, B., Jaulhac, B., Lipsker, D. M., Carapito, C., Boulanger, N., & Ehret‐Sabatier, L. (2015) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m114.046540 · Cited by 30
Mass Spectrometric Immunoassay for the qualitative and quantitative analysis of the cytokine Macrophage Migration Inhibitory Factor (MIF)
Sherma, N. D., Borges, C. R., Trenchevska, O., Jarvis, J. W., Rehder, D. S., Oran, P. E., Nelson, R. W., & Nedelkov, D. (2014) · Proteome Science · doi:10.1186/s12953-014-0052-3 · Cited by 27
Depletion of Abundant Plasma Proteins by Poly(N-isopropylacrylamide-acrylic acid) Hydrogel Particles
Such-Sanmartín, G., Ventura-Espejo, E., & Jensen, O. N. (2014) · Analytical Chemistry · doi:10.1021/ac403749j · Cited by 27
Urothelial cancer proteomics provides both prognostic and functional information
de Velasco, G., Trilla‐Fuertes, L., Gámez‐Pozo, A., Urbanowicz, M., Ruiz-Ares, G., Sepúlveda-Sánchez, J. M., Prado-Vázquez, G., Arevalillo, J. M., Zapater‐Moros, A., Navarro, H., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-15920-6 · Cited by 27
Milk proteome from in silico data aggregation allows the identification of putative biomarkers of negative energy balance in dairy cows
Delosière, M., Pires, J., Bernard, L., Cassar‐Malek, I., & Bonnet, M. (2019) · Scientific Reports · doi:10.1038/s41598-019-46142-7 · Cited by 27
Discovery and Qualification of Serum Protein Biomarker Candidates for Cholangiocarcinoma Diagnosis
Duangkumpha, K., Stoll, T. M., Phetcharaburanin, J., Yongvanit, P., Thanan, R., Techasen, A., Namwat, N., Khuntikeo, N., Chamadol, N., Roytrakul, S., et al. (2019) · Journal of Proteome Research · doi:10.1021/acs.jproteome.9b00242 · Cited by 27
Translational biomarkers in the era of precision medicine
Bravo-Merodio, L., Acharjee, A., Russ, D., Bisht, V., Williams, J. A., Tsaprouni, L., & Gkoutos, G. V. (2020) · Advances in clinical chemistry · doi:10.1016/bs.acc.2020.08.002 · Cited by 28
High-quality and robust protein quantification in large clinical/pharmaceutical cohorts with IonStar proteomics investigation
Shen, S., Wang, X., Zhu, X., Rasam, S. S., Ma, M., Huo, S., Qian, S., Zhang, M., Qu, M., Hu, C., et al. (2022) · Nature Protocols · doi:10.1038/s41596-022-00780-w · Cited by 26
In-Depth Analysis of a Plasma or Serum Proteome Using a 4D Protein Profiling Method
Tang, H., Beer, L. A., & Speicher, D. W. (2011) · Methods in molecular biology · doi:10.1007/978-1-61779-068-3_3 · Cited by 27
Protease profiling of different biofluids in type 1 diabetes mellitus
Caseiro, A., Ferreira, R. M., Quintaneiro, C., Pereira, A., Marinheiro, R., Vitorino, R. M. P., & Amado, F. M. L. (2012) · Clinical Biochemistry · doi:10.1016/j.clinbiochem.2012.08.027 · Cited by 27
Lectin precipitation using phytohemagglutinin‐L 4 coupled to avidin–agarose for serological biomarker discovery in colorectal cancer
Kim, Y.-S., Son, O. L., Lee, J. Y., Kim, S. H., Oh, S., Lee, Y. S., Kim, C., Yoo, J. S., Lee, J. H., Miyoshi, E., et al. (2008) · PROTEOMICS · doi:10.1002/pmic.200800034 · Cited by 27
Proteomics in obesity research
Barceló-Batllori, S., & Gomis, R. (2009) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.200800178 · Cited by 27
Cell-Free miR-27a, a Potential Diagnostic and Prognostic Biomarker for Gastric Cancer
Park, J., Kim, S., Song, K. S., Kim, S., & Kim, S. (2015) · Genomics & Informatics · doi:10.5808/gi.2015.13.3.70 · Cited by 27
Development of a novel, quantitative protein microarray platform for the multiplexed serological analysis of autoantibodies to cancer-testis antigens
Beeton-Kempen, N., Duarte, J. D. G., Shoko, A., Serufuri, J.-M. S., John, T., Cebon, J. S., & Blackburn, J. M. (2014) · International Journal of Cancer · doi:10.1002/ijc.28832 · Cited by 27
Ultrasonic assisted preparation of lanthanide-oleate complexes for the synthesis of multifunctional monodisperse upconversion nanoparticles for multimodal imaging
Tang, S., Wang, J., Yang, C., Dong, L., Kong, D., & Yan, X. (2014) · Nanoscale · doi:10.1039/c4nr00806e · Cited by 27
Quantifying Antibody Binding on Protein Microarrays using Microarray Nonlinear Calibration
Yu, X., Wallstrom, G. L., Magee, D. M., Qiu, J., Mendoza, D. E. A., Wang, J., Bian, X., Graves, M. C., & LaBaer, J. (2013) · BioTechniques · doi:10.2144/000114028 · Cited by 27
Systematic verification of bladder cancer-associated tissue protein biomarker candidates in clinical urine specimens
Tsai, C.-H., Chen, Y., Chang, Y., Hsueh, C., Liu, C., Chang, Y., Chen, C., & Yu, J. (2018) · Oncotarget · doi:10.18632/oncotarget.24578 · Cited by 27
Discovery of Lamin B1 and Vimentin as Circulating Biomarkers for Early Hepatocellular Carcinoma
Wong, K., & Luk, J. M. (2012) · Humana Press eBooks · doi:10.1007/978-1-61779-959-4_19 · Cited by 27
What does it need to be a biomarker? Relationships between resolution, differential quantification and statistical validation of protein surrogate biomarkers
Schrattenholz, A. S., & Groebe, K. (2007) · Electrophoresis · doi:10.1002/elps.200600752 · Cited by 26
Recent technical strategies to identify diagnostic biomarkers for ovarian cancer
Ye, B., Gagnon, A., & Mok, S. C. (2007) · Expert Review of Proteomics · doi:10.1586/14789450.4.1.121 · Cited by 27
Development of Nucleic‐Acid‐Based Electrochemical Biosensors for Clinical Applications
Zhang, Z., Sen, P., Adhikari, B. R., Li, Y., & Soleymani, L. (2022) · Angewandte Chemie · doi:10.1002/ange.202212496 · Cited by 28
A Current State of Proteomics in Adult and Pediatric Inflammatory Bowel Diseases: A Systematic Search and Review
Fabián, O., Bajer, L., Drastich, P., Harant, K., Sticová, E., Ďásková, N., Módos, I., Tichánek, F., & Cahová, M. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24119386 · Cited by 27
Biomarkers and biomarker validation: a pathologist's guide to getting it right
Paver, E. C., & Morey, A. L. (2023) · Pathology · doi:10.1016/j.pathol.2023.11.002 · Cited by 26
Mapping the proteogenomic landscape enables prediction of drug response in acute myeloid leukemia
Pino, J. C., Posso, C., Joshi, S. K., Nestor, M. D., Moon, J., Hansen, J., Hutchinson-Bunch, C. M., Gritsenko, M., Weitz, K., Watanabe‐Smith, K., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101359 · Cited by 26
Stable Cox regression for survival analysis under distribution shifts
Fan, S., Xu, R., Dong, Q., He, Y., Chang, C., & Cui, P. (2024) · Nature Machine Intelligence · doi:10.1038/s42256-024-00932-5 · Cited by 28
Delineating the synovial fluid proteome: Recent advancements and ongoing challenges in biomarker research
Cretu, D., Diamandis, E. P., & Chandran, V. (2013) · Critical Reviews in Clinical Laboratory Sciences · doi:10.3109/10408363.2013.802408 · Cited by 26
Large-Scale SRM Screen of Urothelial Bladder Cancer Candidate Biomarkers in Urine
Duriez, E., Masselon, C., Mesmin, C., Court, M., Demeure, K., Allory, Y., Malats, N., Matondo, M., Radvanyi, F., Garin, J., et al. (2017) · Journal of Proteome Research · doi:10.1021/acs.jproteome.6b00979 · Cited by 25
In-Sample Calibration Curve Using Multiple Isotopologue Reaction Monitoring of a Stable Isotopically Labeled Analyte for Instant LC-MS/MS Bioanalysis and Quantitative Proteomics
Gu, H., Zhao, Y., DeMichele, M., Zheng, N., Zhang, Y. J., Pillutla, R. C., & Zeng, J. (2019) · Analytical Chemistry · doi:10.1021/acs.analchem.8b05656 · Cited by 26
Multi-Omics Approach: New Potential Key Mechanisms Implicated in Cardiorenal Syndromes
Virzì, G. M., Clementi, A., Battaglia, G. G., & Ronco, C. (2019) · Cardiorenal Medicine · doi:10.1159/000497748 · Cited by 27
The diagnostic efficacy of circulating miRNAs in monitoring the early development of colitis‐induced colorectal cancer
El‐Daly, S. M., Morsy, S., Medhat, D., El‐Bana, M. A., Latif, Y. A., Omara, E. A. A., Awadallah, J. R., & Gamal‐Eldeen, A. M. (2019) · Journal of Cellular Biochemistry · doi:10.1002/jcb.28925 · Cited by 26
Genomic, proteomic, and systems biology approaches in biomarker discovery for multiple sclerosis
Huizar, C. C., Raphael, I., & Forsthuber, T. G. (2020) · Cellular Immunology · doi:10.1016/j.cellimm.2020.104219 · Cited by 26
Label-free homogeneous photoelectrochemical aptasensing of VEGF165 based on DNA-regulated peroxidase-mimetic activity of metal-organic-frameworks
Hou, T., Xu, N., Song, X., Yang, L., & Li, F. (2022) · Chinese Chemical Letters · doi:10.1016/j.cclet.2022.107907 · Cited by 26
Application of a Glycoproteomics-Based Biomarker Development Method: Alteration in Glycan Structure on Colony Stimulating Factor 1 Receptor as a Possible Glycobiomarker Candidate for Evaluation of Liver Cirrhosis
Ocho, M., Togayachi, A., Iio, E., Kaji, H., Kuno, A., Sogabe, M., Korenaga, M., Gotoh, M., Tanaka, Y., Ikehara, Y., et al. (2014) · Journal of Proteome Research · doi:10.1021/pr400986t · Cited by 26
Restructuring Proteomics Through Verification
Boja, E. S., Rivers, R. C., Kinsinger, C. R., Mesri, M., Hiltke, T., Rahbar, A. M., & Rodriguez, H. (2010) · Biomarkers in Medicine · doi:10.2217/bmm.10.92 · Cited by 26
Identification and Validation of Loa loa Microfilaria-Specific Biomarkers: a Rational Design Approach Using Proteomics and Novel Immunoassays
Drame, P. M., Meng, Z., Bennuru, S., Herrick, J. A., Veenstra, T. D., & Nutman, T. B. (2016) · mBio · doi:10.1128/mbio.02132-15 · Cited by 26
Use of proteomics for the discovery of early markers of drug toxicity
Collins, B. C., Clarke, A., Kitteringham, N. R., Gallagher, W. M., & Pennington, S. R. (2007) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425225.3.5.689 · Cited by 26
Data Mining for Biomarker Development: A Review of Tissue Specificity Analysis
Klee, E. W. (2008) · Clinics in Laboratory Medicine · doi:10.1016/j.cll.2007.10.009 · Cited by 26
Real-time evaluation of experimental variation in large-scale LC–MS/MS-based quantitative proteomics of complex samples☆
Levin, Y., Wang, L., Ingudomnukul, E., Schwarz, E., Baron‐Cohen, S., Palotás, A., & Bahn, S. (2008) · Journal of Chromatography B · doi:10.1016/j.jchromb.2008.11.007 · Cited by 26
Commercial Immunoassays in Biomarkers Studies: Researchers Beware!
Rifai, N., Watson, I. D., & Miller, W. G. (2012) · Clinical Chemistry · doi:10.1373/clinchem.2012.192351 · Cited by 26
Self-citation
Proteomic analysis of endoscopically (endoscopic pancreatic function test) collected gastroduodenal fluid using in‐gel tryptic digestion followed by LC‐MS/MS
Paulo, J. A., Lee, L., Wu, B. U., Repas, K. A., Banks, P. A., Conwell, D. L., & Steen, H. (2010) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.201000018 · Cited by 25
Mass spectrometry-based membrane proteomics in cancer biomarker discovery
Mermelekas, G., & Zoidakis, J. (2014) · Expert Review of Molecular Diagnostics · doi:10.1586/14737159.2014.917965 · Cited by 26
Plasma proteomic profiling of young and old mice reveals cadherin-13 prevents age-related bone loss
Yang, Y. R., Kabir, M. H., Park, J. H., Park, J.-I., Kang, J. S., Ju, S., Shin, Y. J., Lee, S. M., Lee, J., Kim, S., et al. (2020) · Aging · doi:10.18632/aging.103184 · Cited by 27
Bayesian methods for proteomic biomarker development
Hernández, B., Pennington, S. R., & Parnell, A. C. (2015) · EuPA Open Proteomics · doi:10.1016/j.euprot.2015.08.001 · Cited by 27
Systematic Analytical Validation of Commercial Kits for The Determination of Novel Biomarkers for Clinical Drug Development
Nowatzke, W. L., Cole, T. G., & Bowsher, R. R. (2010) · Bioanalysis · doi:10.4155/bio.09.191 · Cited by 25
Systematic, evidence-based discovery of biomarkers at the NCI
Prensner, J. R., Chinnaiyan, A. M., & Srivastava, S. (2012) · Clinical & Experimental Metastasis · doi:10.1007/s10585-012-9507-z · Cited by 25
Circulating pEGFR Is a Candidate Response Biomarker of Cetuximab Therapy in Colorectal Cancer
Κάτσιλα, Θ., Juliachs, M., Gregori, J., Macarulla, T. M., Villarreal, L., Bardelli, A., Torrance, C. J., Élez, E., Tabernero, J. M., & Villanueva, J. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-0361 · Cited by 25
Water-Soluble Dried Blood Spot in Protein Analysis: A Proof-of-Concept Study
Rosting, C., Gjelstad, A., & Halvorsen, T. G. (2015) · Analytical Chemistry · doi:10.1021/acs.analchem.5b01735 · Cited by 25
Qualification and Verification of Protein Biomarker Candidates
Zhao, Y., & Brasier, A. R. (2016) · Advances in experimental medicine and biology · doi:10.1007/978-3-319-41448-5_23 · Cited by 25
Fast quantitative urinary proteomic profiling workflow for biomarker discovery in kidney cancer
Lin, L., Yu, Q., Zheng, J., Cai, Z., & Tian, R. (2018) · Clinical Proteomics · doi:10.1186/s12014-018-9220-2 · Cited by 25
Mitochondrial Dna Deletions Accurately Detect Endometriosis in Symptomatic Females of Child-Bearing Age
Creed, J. M., Maggrah, A., Reguly, B., & Harbottle, A. (2019) · Biomarkers in Medicine · doi:10.2217/bmm-2018-0419 · Cited by 25
Electrochemical Detection of Vascular Endothelial Growth Factor by Molecularly Imprinted Polymer
Bozal‐Palabiyik, B., Lettieri, M., Uslu, B., & Marrazza, G. (2019) · Electroanalysis · doi:10.1002/elan.201900185 · Cited by 25
Overview and Introduction to Clinical Proteomics
Paik, Y., Kim, H., Lee, E.-Y., Kwon, M., & Cho, S. Y. (2008) · Methods in molecular biology · doi:10.1007/978-1-59745-117-8_1 · Cited by 25
Quantitative proteomics in cardiovascular research: Global and targeted strategies
Shen, X., Young, R. F., Canty, J. M., & Qu, J. (2014) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.201400014 · Cited by 25
Towards proteome standards: The use of absolute quantitation in high-throughput biomarker discovery
Chao, T., Hansmeier, N., & Halden, R. U. (2010) · Journal of Proteomics · doi:10.1016/j.jprot.2010.04.004 · Cited by 24
Getting Absolute: Determining Absolute Protein Quantities via Selected Reaction Monitoring Mass Spectrometry
Ludwig, C., & Aebersold, R. H. (2014) · Royal Society of Chemistry eBooks · doi:10.1039/9781782626985-00080 · Cited by 24
Urinary peptidomics provides a noninvasive humanized readout of diabetic nephropathy in mice
Klein, J., Ramírez‐Torres, A., Ericsson, A., Huang, Y., Breuil, B., Siwy, J., Mischak, H., Peng, X.-R., Bascands, J., & Schanstra, J. P. (2016) · Kidney International · doi:10.1016/j.kint.2016.06.023 · Cited by 24
Proteomics Reveals Plasma Biomarkers for Ischemic Stroke Related to the Coagulation Cascade
Lee, J., Mun, S., Park, A., Kim, D., Lee, Y., Kim, H., Choi, H., Shin, M., Lee, S. J., Kim, J. G., et al. (2020) · Journal of Molecular Neuroscience · doi:10.1007/s12031-020-01545-4 · Cited by 24
Detection of Circulating Serum Protein Biomarkers of Non-Muscle Invasive Bladder Cancer after Protein Corona-Silver Nanoparticles Analysis by SWATH-MS
Gómez, B. B., López-Cortés, R., Nebra, J. C., Vázquez‐Estévez, S., Pérez-Fentes, D., Chantada‐Vázquez, M. D. P., Bravo, S. B., & Núñez, C. (2021) · Nanomaterials · doi:10.3390/nano11092384 · Cited by 24

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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

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

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks