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 201–300 of 1,000

The Alzheimer Precision Medicine Initiative
Hampel, H. J., Initiative, A. P. M., Vergallo, A., Perry, G. L., & Lista, S. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-181121 · Cited by 109
Accurate Mass Measurements in Proteomics
Liu, T., Belov, M. E., Jaitly, N., Qian, W., & Smith, R. D. (2007) · Chemical Reviews · doi:10.1021/cr068288j · Cited by 109
Microfluidic integration for automated targeted proteomic assays
Hughes, A. J., Lin, R., Peehl, D. M., & Herr, A. E. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1108617109 · Cited by 104
Mass-spectrometry-based clinical proteomics – a review and prospective
Parker, C. E., Pearson, T. W., Anderson, N. L., & Borchers, C. H. (2010) · The Analyst · doi:10.1039/c0an00105h · Cited by 108
Biomarker discovery and development in pediatric critical care medicine*
Kaplan, J. M., & Wong, H. R. (2010) · Pediatric Critical Care Medicine · doi:10.1097/pcc.0b013e3181e28876 · Cited by 102
Serum protein profiling by solid phase extraction and mass spectrometry: A future diagnostics tool?
Callesen, A. K., Madsen, J. S., Vach, W., Kruse, T. A., Mogensen, O. E., & Jensen, O. N. (2009) · PROTEOMICS · doi:10.1002/pmic.200800382 · Cited by 104
Comparative Shotgun Proteomics Using Spectral Count Data and Quasi-Likelihood Modeling
Li, M., Gray, W., Zhang, H., Chung, C. H., Billheimer, D. D., Yarbrough, W. G., Liebler, D. C., Shyr, Y., & Slebos, R. J. C. (2010) · Journal of Proteome Research · doi:10.1021/pr100527g · Cited by 103
A novel scavenging tool for cancer biomarker discovery based on the blood-circulating nanoparticle protein corona
Hadjidemetriou, M., Al-Ahmady, Z. S., Buggio, M., Swift, J., & Kostarelos, K. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.10.011 · Cited by 102
Recent developments in mass-spectrometry-based targeted proteomics of clinical cancer biomarkers
Wenk, D., Zuo, C., Kislinger, T., & Sepiashvili, L. (2024) · Clinical Proteomics · doi:10.1186/s12014-024-09452-1 · Cited by 112
SlipChip for Immunoassays in Nanoliter Volumes
Liu, W., Chen, D. L., Du, W., Nichols, K. P., & Ismagilov, R. F. (2010) · Analytical Chemistry · doi:10.1021/ac100044c · Cited by 102
Protein Biomarkers of New-Onset Cardiovascular Disease
Yin, X., Subramanian, S., Hwang, S., O’Donnell, C. J., Fox, C. S., Courchesne, P. L., Muntendam, P., Gordon, N. F., Adourian, A. S., Juhász, P., et al. (2014) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.113.302918 · Cited by 102
Absolute quantitation of endogenous proteins with precision and accuracy using a capillary Western system
Chen, J., Heldman, M. R., Herrmann, M. A., Kedei, N., Woo, W., Blumberg, P. M., & Goldsmith, P. K. (2013) · Analytical Biochemistry · doi:10.1016/j.ab.2013.07.022 · Cited by 99
Urine as a source for clinical proteome analysis: From discovery to clinical application
Rodríguez‐Suárez, E., Siwy, J., Zürbig, P., & Mischak, H. (2013) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2013.06.016 · Cited by 101
Microneedle-based transdermal detection and sensing devices
Wang, J., Lu, Z., Cai, R., Zheng, H., Yu, J., Zhang, Y., & Gu, Z. (2023) · Lab on a Chip · doi:10.1039/d2lc00790h · Cited by 101
Galectin-3 Is a Candidate Biomarker for Amyotrophic Lateral Sclerosis: Discovery by a Proteomics Approach
Zhou, J., Afjehi‐Sadat, L., Asress, S., Duong, D. M., Cudkowicz, M., Glass, J. D., & Peng, J. (2010) · Journal of Proteome Research · doi:10.1021/pr100409r · Cited by 101
Identification of IGFBP2 and IGFBP3 As Compensatory Biomarkers for CA19-9 in Early-Stage Pancreatic Cancer Using a Combination of Antibody-Based and LC-MS/MS-Based Proteomics
Yoneyama, T., Ohtsuki, S., Honda, K., Kobayashi, M., Iwasaki, M., Uchida, Y., Okusaka, T., Nakamori, S., Shimahara, M., Ueno, T., et al. (2016) · PLoS ONE · doi:10.1371/journal.pone.0161009 · Cited by 100
Verification of the Biomarker Candidates for Non-small-cell Lung Cancer Using a Targeted Proteomics Approach
Kim, Y. J., Sertamo, K., Pierrard, M.-A., Mesmin, C., Kim, S.-Y., Schlesser, M., Berchem, G., & Domon, B. (2015) · Journal of Proteome Research · doi:10.1021/pr5010828 · Cited by 98
A General Way to Assay Protein by Coupling Peptide with Signal Reporter via Supermolecule Formation
Li, H., Xie, H., Cao, Y., Ding, X., Yin, Y., & Li, G. (2012) · Analytical Chemistry · doi:10.1021/ac302906c · Cited by 98
Fascin actin-bundling protein 1 in human cancer: Promising biomarker or therapeutic target?
Liu, H., Zhang, Y., Li, L., Cao, J., Guo, Y., Wu, Y., & Gao, W. (2021) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2020.12.014 · Cited by 98
Identifying New Therapeutic Targets via Modulation of Protein Corona Formation by Engineered Nanoparticles
Arvizo, R. R., Giri, K., Moyano, D. F., Miranda, O. R., Madden, B. J., McCormick, D., Bhattacharya, R., Rotello, V. M., Kocher, J., & Mukherjee, P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0033650 · Cited by 99
Proteomics-driven cancer biomarker discovery: looking to the future
Simpson, R. J., Bernhard, O. K., Greening, D. W., & Moritz, R. L. (2008) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2008.02.010 · Cited by 98
The potential and limitations of plasma BNP measurement in the diagnosis, prognosis, and management of children with heart failure due to congenital cardiac disease: an update
Cantinotti, M., Law, Y. M., Vittorini, S., Crocetti, M., Marotta, M., Murzi, B., & Clerico, A. (2014) · Heart Failure Reviews · doi:10.1007/s10741-014-9422-2 · Cited by 97
Total ApoE and ApoE4 Isoform Assays in an Alzheimer's Disease Case-control Study by Targeted Mass Spectrometry (n = 669): A Pilot Assay for Methionine-containing Proteotypic Peptides
Simon, R., Girod, M., Fonbonne, C., Salvador, A., Clément, Y., Lantéri, P., Amouyel, P., Lambert, J. C., & Lemoine, J. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m112.018861 · Cited by 92
Biomarkers in the Age of Omics: Time for a Systems Biology Approach
Abu-Asab, M. S., Chaouchi, M., Alesci, S., Galli, S., Laassri, M., Cheema, A. K., Atouf, F., VanMeter, J. W., & Amri, H. (2011) · OMICS A Journal of Integrative Biology · doi:10.1089/omi.2010.0023 · Cited by 97
Early Detection of Ovarian Cancer
Das, P. M., & Bast, R. C. (2008) · Biomarkers in Medicine · doi:10.2217/17520363.2.3.291 · Cited by 96
Mass Spectrometry (LC-MS/MS) Site-Mapping of N-Glycosylated Membrane Proteins for Breast Cancer Biomarkers
Whelan, S. A., Lu, M., He, J., Yan, W., Saxton, R. E., Faull, K. F., Whitelegge, J. P., & Chang, H. R. (2009) · Journal of Proteome Research · doi:10.1021/pr900322g · Cited by 95
Fibronectin is a serum biomarker for D uchenne muscular dystrophy
Martin, F. C., Hiller, M., Spitali, P., Oonk, S., Dalebout, H., Palmblad, M., Chaouch, A., Guglieri, M., Straub, V. W., Lochmüller, H., et al. (2014) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.201300072 · Cited by 96
Proteomics Applications in Health: Biomarker and Drug Discovery and Food Industry.
Dashatan, N. A., Koushki, M., Abbaszadeh, H., Rostami‐Nejad, M., & Rezaei–Tavirani, M. (2018) · Europe PMC (PubMed Central) · Cited by 96
Exhaled Endogenous Particles Contain Lung Proteins
Bredberg, A., Gobom, J., Almstrand, A., Larsson, P., Blennow, K., Olin, A., & Mirgorodskaya, E. E. (2011) · Clinical Chemistry · doi:10.1373/clinchem.2011.169235 · Cited by 94
Proteomic Biomarker Discovery in 1000 Human Plasma Samples with Mass Spectrometry
Cominetti, O., Galindo, A. N., Corthésy, J., Moreno, S. O., Irincheeva, I., Valsesia, A., Astrup, A. V., Saris, W. H. M., Hager, J., Kussmann, M., et al. (2015) · Journal of Proteome Research · doi:10.1021/acs.jproteome.5b00901 · Cited by 94
Development of a multiplexed giant magnetoresistive biosensor array prototype to quantify ovarian cancer biomarkers
Klein, T., Wang, W., Yu, L., Wu, K., Boylan, K. L. M., Vogel, R. I., Skubitz, A. P. N., & Wang, J. (2018) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2018.10.046 · Cited by 93
Sensitive detection of multiple blood biomarkers via immunomagnetic exosomal PCR for the diagnosis of Alzheimer’s disease
Shun, H., Zhang, L., Su, Y., Liang, X., Yang, J., Luo, Q., & Luo, H. (2024) · Science Advances · doi:10.1126/sciadv.abm3088 · Cited by 98
Application of LC/MS to proteomics studies: current status and future prospects
Chen, G., & Pramanik, B. N. (2009) · Drug Discovery Today · doi:10.1016/j.drudis.2009.02.007 · Cited by 94
Challenges in translating plasma proteomics from bench to bedside: update from the NHLBI Clinical Proteomics Programs
Gerszten, R. E., Accurso, F. J., Bernard, G. R., Caprioli, R. M., Klee, E. W., Klee, G. G., Kullo, I. J., Laguna, T. A., Roth, F. P., Sabatine, M. S., et al. (2008) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00044.2008 · Cited by 93
A bibliometric analysis of research on proteomics in Science Citation Index Expanded
Tan, J., Fu, H., & Ho, Y. (2013) · Scientometrics · doi:10.1007/s11192-013-1125-2 · Cited by 100
Genome-wide epigenomic profiling for biomarker discovery
Dirks, R. A. M., Stunnenberg, H. G., & Marks, H. (2016) · Clinical Epigenetics · doi:10.1186/s13148-016-0284-4 · Cited by 94
Development of the DNA-based biosensors for high performance in detection of molecular biomarkers: More rapid, sensitive, and universal
Wang, Q., Wang, J., Huang, Y. L., Du, Y., Zhang, Y., Cui, Y., & Kong, D. (2021) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2021.113739 · Cited by 98
Advances in Genomic Data and Biomarkers: Revolutionizing NSCLC Diagnosis and Treatment
Restrepo, J. C., Dueñas, D., Corredor, Z., & Liscano, Y. (2023) · Cancers · doi:10.3390/cancers15133474 · Cited by 99
Directed mass spectrometry: towards hypothesis-driven proteomics
Schmidt, A., Claassen, M., & Aebersold, R. H. (2009) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2009.08.016 · Cited by 93
Identification of Differentially Expressed Proteins in Direct Expressed Prostatic Secretions of Men with Organ-confined Versus Extracapsular Prostate Cancer
Kim, Y., Ignatchenko, V., Yao, C. Q., Kalatskaya, I., Nyalwidhe, J. O., Lance, R. S., Gramolini, A. O., Troyer, D. A., Stein, L. D., Boutros, P. C., et al. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m112.017889 · Cited by 92
Cell surface-based sensing with metallic nanoparticles
Jiang, Z., Le, N. D. B., Gupta, A., & Rotello, V. M. (2015) · Chemical Society Reviews · doi:10.1039/c4cs00387j · Cited by 91
Evaluation of Strong Cation Exchange versus Isoelectric Focusing of Peptides for Multidimensional Liquid Chromatography-Tandem Mass Spectrometry
Slebos, R. J. C., Brock, J. W. C., Winters, N. F., Stuart, S. R., Martinez, M. A., Li, M., Chambers, M. C., Zimmerman, L. J., Ham, A. L., Tabb, D. L., et al. (2008) · Journal of Proteome Research · doi:10.1021/pr8004666 · Cited by 91
Identification and verification of heat shock protein 60 as a potential serum marker for colorectal cancer
Hamelin, C., Cornut, E., Poirier, F., Pons, S., Beaulieu, C., Charrier, J., Haïdous, H., Cotte, E., Lambert, C., Piard, F., et al. (2011) · FEBS Journal · doi:10.1111/j.1742-4658.2011.08385.x · Cited by 91
Quantitative mass spectrometry-based techniques for clinical use: Biomarker identification and quantification☆
Simpson, K., Whetton, A. D., & Dive, C. (2008) · Journal of Chromatography B · doi:10.1016/j.jchromb.2008.11.023 · Cited by 94
Application of Label-free Quantitative Peptidomics for the Identification of Urinary Biomarkers of Kidney Chronic Allograft Dysfunction
Quintana, L. F., Campistol, J. M., Alcolea, M. P., Bañón-Maneus, E., Sol-González, A., & Cutillas, P. R. (2009) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m900059-mcp200 · Cited by 91
What is a biomarker? Research investments and lack of clinical integration necessitate a review of biomarker terminology and validation schema
Ptolemy, A. S., & Rifai, N. (2010) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.3109/00365513.2010.493354 · Cited by 90
Self-citation
Challenges and Opportunities in Clinical Applications of Blood-Based Proteomics in Cancer
Bhawal, R. P., Oberg, A. L., Zhang, S., & Kohli, M. (2020) · Cancers · doi:10.3390/cancers12092428 · Cited by 92
Proteomics of human biological fluids for biomarker discoveries: technical advances and recent applications
Dayon, L., Cominetti, O., & Affolter, M. (2022) · Expert Review of Proteomics · doi:10.1080/14789450.2022.2070477 · Cited by 93
Development of Nucleic‐Acid‐Based Electrochemical Biosensors for Clinical Applications
Zhang, Z., Sen, P., Adhikari, B. R., Li, Y., & Soleymani, L. (2022) · Angewandte Chemie International Edition · doi:10.1002/anie.202212496 · Cited by 91
Emerging Biomarkers in Metabolomics: Advancements in Precision Health and Disease Diagnosis
Vo, D.-K., & Trinh, K. T. L. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252313190 · Cited by 98
Applications of protein microarrays for biomarker discovery
Ramachandran, N., Srivastava, S., & LaBaer, J. (2008) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.200800032 · Cited by 90
Mining the archival formalin-fixed paraffin-embedded tissue proteome: opportunities and challenges
Nirmalan, N. J., Harnden, P., Selby, P. J., & Banks, R. E. (2008) · Molecular BioSystems · doi:10.1039/b800098k · Cited by 90
Comparison of standard- and nano-flow liquid chromatography platforms for MRM-based quantitation of putative plasma biomarker proteins
Percy, A. J., Chambers, A. G., Yang, J., Domański, D., & Borchers, C. H. (2012) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-012-6010-y · Cited by 90
Inkjet-printed point-of-care immunoassay on a nanoscale polymer brush enables subpicomolar detection of analytes in blood
Joh, D. Y., Hucknall, A., Wei, Q., Mason, K. A., Lund, M. L., Fontes, C. M., Hill, R. T., Blair, R., Zimmers, Z. A., Achar, R. K., et al. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1703200114 · Cited by 89
Systematic Comparison of Fractionation Methods for In-depth Analysis of Plasma Proteomes
Cao, Z., Tang, H., Wang, H., Liu, Q., & Speicher, D. W. (2012) · Journal of Proteome Research · doi:10.1021/pr201068b · Cited by 89
Reconstruction of a robust glycodiagnostic agent supported by multiple lectin‐assisted glycan profiling
Kuno, A., Sato, T., Shimazaki, H., Unno, S., Saitou, K., Kiyohara, K., Sogabe, M., Tsuruno, C., Takahama, Y., Ikehara, Y., et al. (2013) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.201300010 · Cited by 88
Detection of multiplex exosomal miRNAs for clinically accurate diagnosis of Alzheimer’s disease using label-free plasmonic biosensor based on DNA-Assembled advanced plasmonic architecture
Song, S., Lee, J. U., Jeon, M. J., Kim, S., & Sim, S. J. (2022) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2021.113864 · Cited by 88
Machine Learning-based Classification of Diffuse Large B-cell Lymphoma Patients by Their Protein Expression Profiles
Deeb, S. J., Tyanova, S., Hummel, M., Schmidt‐Supprian, M., Cox, J., & Mann, M. (2015) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m115.050245 · Cited by 89
Mass spectrometry for translational proteomics: progress and clinical implications
Baker, E. S., Liu, T., Petyuk, V., Burnum-Johnson, K., Ibrahim, Y., Anderson, G., & Smith, R. D. (2012) · Genome Medicine · doi:10.1186/gm364 · Cited by 94
Pathway-Based Biomarker Search by High-Throughput Proteomics Profiling of Secretomes
Lawlor, K., Nazarian, A., Lacomis, L., Tempst, P., & Villanueva, J. (2009) · Journal of Proteome Research · doi:10.1021/pr8008572 · Cited by 88
Nutrigenomics and Personalized Diets: What Will They Mean for Food?
German, J. B., Zivkovic, A. M., Dallas, D. C., & Smilowitz, J. T. (2011) · Annual Review of Food Science and Technology · doi:10.1146/annurev.food.102308.124147 · Cited by 90
Reduced Intra-individual Reaction Time Variability During a Go–NoGo Task in Detoxified Alcohol-Dependent Patients After One Right-Sided Dorsolateral Prefrontal HF-rTMS Session
Herremans, S. C., Vanderhasselt, M., Raedt, R. D., & Baeken, C. (2013) · Alcohol and Alcoholism · doi:10.1093/alcalc/agt054 · Cited by 87
An Optical Nanoruler Based on a Conjugated Polymer−Silver Nanoprism Pair for Label‐Free Protein Detection
Wang, X., Li, S., Zhang, P., Lv, F., Liu, L., Li, L., & Wang, S. (2015) · Advanced Materials · doi:10.1002/adma.201502880 · Cited by 86
A targeted proteomic strategy for the measurement of oral cancer candidate biomarkers in human saliva
Kawahara, R., Bollinger, J. G., Rivera, C., Ribeiro, A. C. P., Brandão, T. B., Leme, A. F. P., & MacCoss, M. J. (2015) · PROTEOMICS · doi:10.1002/pmic.201500224 · Cited by 86
Mass spectrometry of peptides and proteins from human blood
Zhu, P., Bowden, P., Zhang, D., & Marshall, J. G. (2010) · Mass Spectrometry Reviews · doi:10.1002/mas.20291 · Cited by 78
MRMer, an Interactive Open Source and Cross-platform System for Data Extraction and Visualization of Multiple Reaction Monitoring Experiments
Martin, D. B., Holzman, T., May, D., Peterson, A. C., Eastham, A., Eng, J. K., & McIntosh, M. W. (2008) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m700504-mcp200 · Cited by 86
SERS Aptatags: New Responsive Metallic Nanostructures for Heterogeneous Protein Detection by Surface Enhanced Raman Spectroscopy
Fabris, L., Dante, M., Nguyen, T., Tok, J. B. ‐., & Bazan, G. C. (2008) · Advanced Functional Materials · doi:10.1002/adfm.200800301 · Cited by 86
The discovery and development of proteomic safety biomarkers for the detection of drug-induced liver toxicity
Amacher, D. E. (2010) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2010.02.011 · Cited by 85
Advanced nanomaterials as sample technique for bio-analysis
Sun, N., Yu, H., Wu, H., Shen, X., & Deng, C. (2021) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2020.116168 · Cited by 85
Counting sperm does not add up any more: time for a new equation?
Lefièvre, L., Bedu-Addo, K., Conner, S. J., Machado-Oliveira, G., Chen, Y., Kirkman‐Brown, J., Afnan, M., Publicover, S. J., Ford, W. C. L., & Barratt, C. L. R. (2007) · Reproduction · doi:10.1530/rep-06-0332 · Cited by 85
Cytokines as Biomarkers of Pancreatic Ductal Adenocarcinoma: A Systematic Review
Yako, Y. Y., Kruger, D., Smith, M., & Brand, M. (2016) · PLoS ONE · doi:10.1371/journal.pone.0154016 · Cited by 87
Targeted Quantification of Low ng/mL Level Proteins in Human Serum without Immunoaffinity Depletion
Shi, T., Sun, X., Gao, Y., Fillmore, T., Schepmoes, A., Zhao, R., He, J., Moore, R., Kagan, J., Rodland, K., et al. (2013) · Journal of Proteome Research · doi:10.1021/pr400178v · Cited by 79
Accurate Quantification of Cardiovascular Biomarkers in Serum Using Protein Standard Absolute Quantification (PSAQ™) and Selected Reaction Monitoring
Huillet, C., Adrait, A., Lebert, D., Picard, G., Trauchessec, M., Louwagie, M., Dupuis, A., Hittinger, L., Ghaleh, B., Corvoisier, P. L., et al. (2011) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.008235 · Cited by 84
Going retro: Oxidative stress biomarkers in modern redox biology
Margaritelis, N. V., Cobley, J. N., Paschalis, V., Veskoukis, A. S., Theodorou, A. A., Kyparos, A., & Nikolaidis, M. G. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.02.005 · Cited by 84
Kidney Disease and the Nexus of Chronic Kidney Disease and Acute Kidney Injury
Yerramilli, M., Farace, G., Quinn, J., & Yerramilli, M. (2016) · Veterinary Clinics of North America Small Animal Practice · doi:10.1016/j.cvsm.2016.06.011 · Cited by 99
High throughput and accurate serum proteome profiling by integrated sample preparation technology and single-run data independent mass spectrometry analysis
Lin, L., Zheng, J., Yu, Q., Chen, W., Xing, J., Chen, C., & Tian, R. (2017) · Journal of Proteomics · doi:10.1016/j.jprot.2017.12.014 · Cited by 84
Sources of urinary proteins and their analysis by urinary proteomics for the detection of biomarkers of disease
Julian, B. A., Suzuki, H., Suzuki, Y., Tomino, Y., Spasovski, G. B., & Novák, J. (2009) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.200800243 · Cited by 84
“Product Ion Monitoring” Assay for Prostate-Specific Antigen in Serum Using a Linear Ion-Trap
Kulasingam, V., Smith, C. R., Batruch, I., Buckler, A., Jeffery, D. A., & Diamandis, E. P. (2008) · Journal of Proteome Research · doi:10.1021/pr7005999 · Cited by 84
Global Stability of Plasma Proteomes for Mass Spectrometry-Based Analyses
Zimmerman, L. J., Li, M., Yarbrough, W. G., Slebos, R. J. C., & Liebler, D. C. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m111.014340 · Cited by 85
Combination of Improved 18O Incorporation and Multiple Reaction Monitoring: A Universal Strategy for Absolute Quantitative Verification of Serum Candidate Biomarkers of Liver Cancer
Zhao, Y., Jia, W., Sun, W., Jin, W., Guo, L., Wei, J., Ying, W., Zhang, Y., Xie, Y., Jiang, Y., et al. (2010) · Journal of Proteome Research · doi:10.1021/pr9011969 · Cited by 82
Systematic quantification of peptides/proteins in urine using selected reaction monitoring
Selevsek, N., Matondo, M., Sänchez‐Carbayo, M., Aebersold, R. H., & Domon, B. (2011) · PROTEOMICS · doi:10.1002/pmic.201000599 · Cited by 82
Decoding the glycoproteome: a new frontier for biomarker discovery in cancer
He, K., Baniasad, M., Kwon, H., Čaval, T., Xu, G., Lebrilla, C. B., Hommes, D. W., & Bertozzi, C. R. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01532-x · Cited by 86
In-Depth Proteomics of Ovarian Cancer Ascites: Combining Shotgun Proteomics and Selected Reaction Monitoring Mass Spectrometry
Elschenbroich, S., Ignatchenko, V., Clarke, B. A., Kalloger, S. E., Boutros, P. C., Gramolini, A. O., Shaw, P. H., Jurišica, I., & Kislinger, T. (2011) · Journal of Proteome Research · doi:10.1021/pr1011087 · Cited by 82
Unbiased plasma proteomics for novel diagnostic biomarkers in cardiovascular disease: identification of quiescin Q6 as a candidate biomarker of acutely decompensated heart failure
Mebazaa, A., Vanpoucke, G., Thomas, G. R., Verleysen, K., Solal, A. C., Vanderheyden, M., Bartúnek, J., Mueller, C. E., Launay, J., Landuyt, N. V., et al. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehs162 · Cited by 82
Mass-Spectrometry Based Proteome Comparison of Extracellular Vesicle Isolation Methods: Comparison of ME-kit, Size-Exclusion Chromatography, and High-Speed Centrifugation
Askeland, A., Borup, A., Østergaard, O., Olsen, J. V., Lund, S. M., Christiansen, G., Kristensen, S. R., Heegaard, N. H. H., & Pedersen, S. (2020) · Biomedicines · doi:10.3390/biomedicines8080246 · Cited by 81
Dual-Mode Sensing Platform for Cancer Antigen 15-3 Determination Based on a Silica Nanochannel Array Using Electrochemiluminescence and Electrochemistry
Huang, J., Zhang, T., Zheng, Y., & Liu, J. (2023) · Biosensors · doi:10.3390/bios13030317 · Cited by 81
Why have so few proteomic biomarkers “survived” validation? (Sample size and independent validation considerations)
Hernández, B., Parnell, A. C., & Pennington, S. R. (2014) · PROTEOMICS · doi:10.1002/pmic.201300377 · Cited by 81
Statistical Considerations of Optimal Study Design for Human Plasma Proteomics and Biomarker Discovery
Zhou, C., Simpson, K., Lancashire, L., Walker, M. J., Dawson, M. J., Unwin, R. D., Rembielak, A., Price, P., West, C., Dive, C., et al. (2012) · Journal of Proteome Research · doi:10.1021/pr200636x · Cited by 81
PSAQ™ standards for accurate MS–based quantification of proteins: from the concept to biomedical applications
Picard, G., Lebert, D., Louwagie, M., Adrait, A., Huillet, C., Vandenesch, F., Bruley, C., Garin, J., Jaquinod, M., & Brun, V. (2012) · Journal of Mass Spectrometry · doi:10.1002/jms.3106 · Cited by 79
The role of metabolomics in neonatal and pediatric laboratory medicine
Mussap, M., Antonucci, R., Noto, A., & Fanos, V. (2013) · Clinica Chimica Acta · doi:10.1016/j.cca.2013.08.020 · Cited by 80
Early biomarkers of joint damage in rheumatoid and psoriatic arthritis
Ardle, A. M., Flatley, B., Pennington, S. R., & FitzGerald, O. (2015) · Arthritis Research & Therapy · doi:10.1186/s13075-015-0652-z · Cited by 80
Nanoproteomics enables proteoform-resolved analysis of low-abundance proteins in human serum
Tiambeng, T. N., Roberts, D. S., Brown, K. A., Zhu, Y., Chen, B., Wu, Z., Mitchell, S. D., Guardado-Alvarez, T. M., Jin, S., & Ge, Y. (2020) · Nature Communications · doi:10.1038/s41467-020-17643-1 · Cited by 76
Initial Development and Validation of a Novel Extraction Method for Quantitative Mining of the Formalin-Fixed, Paraffin-Embedded Tissue Proteome for Biomarker Investigations
Nirmalan, N. J., Hughes, C., Peng, J., McKenna, T., Langridge, J., Cairns, D. A., Harnden, P., Selby, P. J., & Banks, R. E. (2010) · Journal of Proteome Research · doi:10.1021/pr100812d · Cited by 79
Construction and bioapplications of aptamer-based dual recognition strategy
Wang, Y., Liu, X., Wu, L., Ding, L., Effah, C. Y., Wu, Y., Xiong, Y., & He, L. (2021) · Biosensors and Bioelectronics · doi:10.1016/j.bios.2021.113661 · Cited by 79
Detection of biomarkers using recombinant antibodies coupled to nanostructured platforms
Kierny, M. R., Cunningham, T. D., & Kay, B. K. (2012) · Nano Reviews · doi:10.3402/nano.v3i0.17240 · Cited by 78
Enzymes and related proteins as cancer biomarkers: A proteomic approach
Liang, S.-L., & Chan, D. W. (2007) · Clinica Chimica Acta · doi:10.1016/j.cca.2007.02.017 · Cited by 79
Differential profiling of breast cancer plasma proteome by isotope-coded affinity tagging method reveals biotinidase as a breast cancer biomarker
Kang, U., Ahn, Y., Lee, J. W., Kim, Y., Kim, J., Yu, M., Noh, D., & Lee, C. (2010) · BMC Cancer · doi:10.1186/1471-2407-10-114 · Cited by 79
Unconventional Secretion is a Major Contributor of Cancer Cell Line Secretomes
Villarreal, L., Méndez, O., Salvans, C., Gregori, J., Baselga, J. M., & Villanueva, J. (2012) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m112.021618 · Cited by 79
Comparative Profiling of Serum Glycoproteome by Sequential Purification of Glycoproteins and 2-Nitrobenzenesulfenyl (NBS) Stable Isotope Labeling: A New Approach for the Novel Biomarker Discovery for Cancer
Ueda, K., Katagiri, T., Shimada, T., Irie, S., Sato, T., Nakamura, Y., & Daigo, Y. (2007) · Journal of Proteome Research · doi:10.1021/pr070103h · Cited by 78
Ion mobility-mass spectrometry of intact protein–ligand complexes for pharmaceutical drug discovery and development
Niu, S., Rabuck-Gibbons, J. N., & Ruotolo, B. T. (2013) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2013.06.019 · Cited by 77

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