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Molecular & Cellular Proteomics 1:845-867, 2002.
© 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
Reviews/Perspectives
The Human Plasma Proteome
History, Character, and Diagnostic Prospects*
From The Plasma Proteome Institute, Washington, D. C. 20009-3450
The human plasma proteome holds the promise of a revolution in disease diagnosis and therapeutic monitoring provided that major challenges in proteomics and related disciplines can be addressed. Plasma is not only the primary clinical specimen but also represents the largest and deepest version of the human proteome present in any sample: in addition to the classical "plasma proteins," it contains all tissue proteins (as leakage markers) plus very numerous distinct immunoglobulin sequences, and it has an extraordinary dynamic range in that more than 10 orders of magnitude in concentration separate albumin and the rarest proteins now measured clinically. Although the restricted dynamic range of conventional proteomic technology (two-dimensional gels and mass spectrometry) has limited its contribution to the list of 289 proteins (tabulated here) that have been reported in plasma to date, very recent advances in multidimensional survey techniques promise at least double this number in the near future. Abundant scientific evidence, from proteomics and other disciplines, suggests that among these are proteins whose abundances and structures change in ways indicative of many, if not most, human diseases. Nevertheless, only a handful of proteins are currently used in routine clinical diagnosis, and the rate of introduction of new protein tests approved by the United States Food and Drug Administration (FDA) has paradoxically declined over the last decade to less than one new protein diagnostic marker per year. We speculate on the reasons behind this large discrepancy between the expectations arising from proteomics and the realities of clinical diagnostics and suggest approaches by which protein-disease associations may be more effectively translated into diagnostic tools in the future.
To whom correspondence should be addressed: The Plasma Proteome Inst., P.O. Box 53450, Washington, D. C. 20009-3450. Fax: 202-234-9175; E-mail: leighanderson{at}plasmaproteome.org
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M. S. Lowenthal, A. I. Mehta, K. Frogale, R. W. Bandle, R. P. Araujo, B. L. Hood, T. D. Veenstra, T. P. Conrads, P. Goldsmith, D. Fishman, et al. Analysis of Albumin-Associated Peptides and Proteins from Ovarian Cancer Patients Clin. Chem., October 1, 2005; 51(10): 1933 - 1945. [Abstract] [Full Text] [PDF]
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S. Mian, S. Ugurel, E. Parkinson, I. Schlenzka, I. Dryden, L. Lancashire, G. Ball, C. Creaser, R. Rees, and D. Schadendorf Serum Proteomic Fingerprinting Discriminates Between Clinical Stages and Predicts Disease Progression in Melanoma Patients J. Clin. Oncol., August 1, 2005; 23(22): 5088 - 5093. [Abstract] [Full Text] [PDF]
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E. M Scott, A. M Carter, and J. B. Findlay The application of proteomics to diabetes Diabetes and Vascular Disease Research, May 1, 2005; 2(2): 54 - 60. [Abstract] [PDF]
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H. Molina, J. Bunkenborg, G. H. Reddy, B. Muthusamy, P. J. Scheel, and A. Pandey A Proteomic Analysis of Human Hemodialysis Fluid Mol. Cell. Proteomics, May 1, 2005; 4(5): 637 - 650. [Abstract] [Full Text] [PDF]
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W.-J. Qian, M. E. Monroe, T. Liu, J. M. Jacobs, G. A. Anderson, Y. Shen, R. J. Moore, D. J. Anderson, R. Zhang, S. E. Calvano, et al. Quantitative Proteome Analysis of Human Plasma following in Vivo Lipopolysaccharide Administration Using 16O/18O Labeling and the Accurate Mass and Time Tag Approach Mol. Cell. Proteomics, May 1, 2005; 4(5): 700 - 709. [Abstract] [Full Text] [PDF]
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T. D. Veenstra, T. P. Conrads, B. L. Hood, A. M. Avellino, R. G. Ellenbogen, and R. S. Morrison Biomarkers: Mining the Biofluid Proteome Mol. Cell. Proteomics, April 1, 2005; 4(4): 409 - 418. [Abstract] [Full Text] [PDF]
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R. Chen, S. Pan, T. A. Brentnall, and R. Aebersold Proteomic Profiling of Pancreatic Cancer for Biomarker Discovery Mol. Cell. Proteomics, April 1, 2005; 4(4): 523 - 533. [Abstract] [Full Text] [PDF]
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M. E. Wright, D. K. Han, and R. Aebersold Mass Spectrometry-based Expression Profiling of Clinical Prostate Cancer Mol. Cell. Proteomics, April 1, 2005; 4(4): 545 - 554. [Abstract] [Full Text] [PDF]
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 L. Anderson Candidate-based proteomics in the search for biomarkers of cardiovascular disease J. Physiol., February 15, 2005; 563(1): 23 - 60. [Abstract] [Full Text] [PDF]
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H. Zhang, E. C. Yi, X.-j. Li, P. Mallick, K. S. Kelly-Spratt, C. D. Masselon, D. G. Camp II, R. D. Smith, C. J. Kemp, and R. Aebersold High Throughput Quantitative Analysis of Serum Proteins Using Glycopeptide Capture and Liquid Chromatography Mass Spectrometry Mol. Cell. Proteomics, February 1, 2005; 4(2): 144 - 155. [Abstract] [Full Text] [PDF]
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J.-H. Chen, Y.-W. Chang, C.-W. Yao, T.-S. Chiueh, S.-C. Huang, K.-Y. Chien, A. Chen, F.-Y. Chang, C.-H. Wong, and Y.-J. Chen Plasma proteome of severe acute respiratory syndrome analyzed by two-dimensional gel electrophoresis and mass spectrometry PNAS, December 7, 2004; 101(49): 17039 - 17044. [Abstract] [Full Text] [PDF]
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 B. A. Wetmore and B. A. Merrick Invited Review: Toxicoproteomics: Proteomics Applied to Toxicology and Pathology Toxicol Pathol, October 1, 2004; 32(6): 619 - 642. [Abstract] [PDF]
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T. Pisitkun, R.-F. Shen, and M. A. Knepper Identification and proteomic profiling of exosomes in human urine PNAS, September 7, 2004; 101(36): 13368 - 13373. [Abstract] [Full Text] [PDF]
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 J. Hirsch, K. C. Hansen, A. L. Burlingame, and M. A. Matthay Proteomics: current techniques and potential applications to lung disease Am J Physiol Lung Cell Mol Physiol, July 1, 2004; 287(1): L1 - L23. [Abstract] [Full Text] [PDF]
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T. Z. Kristiansen, J. Bunkenborg, M. Gronborg, H. Molina, P. J. Thuluvath, P. Argani, M. G. Goggins, A. Maitra, and A. Pandey A Proteomic Analysis of Human Bile Mol. Cell. Proteomics, July 1, 2004; 3(7): 715 - 728. [Abstract] [Full Text] [PDF]
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N. L. Anderson, M. Polanski, R. Pieper, T. Gatlin, R. S. Tirumalai, T. P. Conrads, T. D. Veenstra, J. N. Adkins, J. G. Pounds, R. Fagan, et al. The Human Plasma Proteome: A Nonredundant List Developed by Combination of Four Separate Sources Mol. Cell. Proteomics, April 1, 2004; 3(4): 311 - 326. [Abstract] [Full Text] [PDF]
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J. W. Zolg and H. Langen How Industry Is Approaching the Search for New Diagnostic Markers and Biomarkers Mol. Cell. Proteomics, April 1, 2004; 3(4): 345 - 354. [Abstract] [Full Text] [PDF]
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 E. McGregor and M. J. Dunn Proteomics of heart disease Hum. Mol. Genet., October 15, 2003; 12(90002): R135 - 144. [Abstract] [Full Text] [PDF]
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R. S. Tirumalai, K. C. Chan, D. A. Prieto, H. J. Issaq, T. P. Conrads, and T. D. Veenstra Characterization of the Low Molecular Weight Human Serum Proteome Mol. Cell. Proteomics, October 1, 2003; 2(10): 1096 - 1103. [Abstract] [Full Text] [PDF]
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N. Guerreiro, F. Staedtler, O. Grenet, J. Kehren, and S.-D. Chibout Toxicogenomics in Drug Development Toxicol Pathol, August 1, 2003; 31(5): 471 - 479. [Abstract] [PDF]
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E. Petricoin III and L. A. Liotta The Vision for a New Diagnostic Paradigm Clin. Chem., August 1, 2003; 49(8): 1276 - 1278. [Full Text] [PDF]
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H. Hondermarck Breast Cancer: When Proteomics Challenges Biological Complexity Mol. Cell. Proteomics, May 1, 2003; 2(5): 281 - 291. [Abstract] [Full Text] [PDF]
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L. F. Steel, M. G. Trotter, P. B. Nakajima, T. S. Mattu, G. Gonye, and T. Block Efficient and Specific Removal of Albumin from Human Serum Samples Mol. Cell. Proteomics, April 1, 2003; 2(4): 262 - 270. [Abstract] [Full Text] [PDF]
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