EDITOR-IN-CHIEF
editor ial
William S. Hancock Barnett Institute and Department of Chemistry Northeastern University 360 Huntington Avenue 341 Mugar Bldg. Boston, MA 02115 617-373-4881; Fax: 617-373-2855
[email protected] A Profound State of Ignorance
ASSOCIATE EDITORS
Joshua LaBaer Harvard Medical School
György Marko-Varga AstraZeneca and Lund University
EDITORIAL ADVISORY BOARD
Ruedi H. Aebersold Institute for Systems Biology
Leigh Anderson Plasma Proteome Institute
Ettore Appella National Cancer Institute
Rolf Apweiler European Bioinformatics Institute
Ronald Beavis Manitoba Centre for Proteomics
Walter Blackstock Cellzome
Brian Chait The Rockefeller University
Patrick L. Coleman 3M
Christine Colvis National Institutes of Health
Catherine Fenselau University of Maryland
Daniel Figeys MDS Proteomics
Sam Hanash University of Michigan
Stanley Hefta Bristol-Myers Squibb
Donald F. Hunt University of Virginia
Barry L. Karger Northeastern University
Daniel C. Liebler Vanderbilt University School of Medicine
Lance Liotta National Cancer Institute
Matthias Mann University of Southern Denmark
Stephen A. Martin Applied Biosystems
Jeremy Nicholson Imperial College of London
Gilbert S. Omenn University of Michigan
Emanuel Petricoin Food and Drug Administration
J. Michael Ramsey Oak Ridge National Laboratory
Pier Giorgio Righetti University of Verona
John T. Stults Biospect
Peter Wagner
n proteomics, as in clinical chemistry, it is well accepted that plasma or serum is the ultimate diagnostic fluid. A blood sample represents the summation of metabolic events in a wide variety of fluids and tissues and thus offers the opportunity to assess the status of an individual’s health. For this reason, clinical laboratories are well organized to collect blood samples, and this is done for many individuals on an annual basis. Most clinical repositories consist of stored serum samples and so retrospective studies usually involve serum analysis. The collection of plasma occurs on a large scale in a multinational effort involving organizations such as the Red Cross. In addition, pharmaceutical companies prepare protein fractions for disease treatments. Plasma is also used to replace blood lost during surgery and other medical procedures. Finally, a tremendous amount of excellent clinical research has measured the activity of diagnostically important proteins. For example, immunological measurements such as ELISAs can provide sensitive measurements of cytokines and other low-level proteins. With all of this background, one would readily assume that we understand well the protein components of plasma or serum. However, thanks to the sequencing of the human genome, DNA sequences for undiscovered proteins are available, and we can identify such proteins in a proteomic analysis based on peptide fragments and MS measurements. We are starting to find that this new approach will yield information about many proteins, even the abundant ones; although we have just begun this exciting voyage, there are already hints of many unexpected discoveries. Currently, the sources of this information are the initial studies of plasma and serum proteomics, and now the Human Proteome Organization (HUPO) is preparing an exhaustive report of its multi-investigator study. I would like to describe two examples from my laboratory that raise a question about the real state of our knowledge about this important fluid. One example is the protein afamin, which is of medium abundance in our analyses and is common in proteomic plasma and serum analyses. There is, however, no literature on this protein. It has only been identified as a gene sequence, though on the basis of homology it may serve as a transport protein. This is clearly an example of a major blood protein that had not been discovered in the pre-genomic era. Another example is the pregnancy zone protein, which derives its name from the fact that it shows the greatest increase in the blood during pregnancy. Despite this, the function of this protein is currently unknown. We first observed it in the analysis of serum samples from breast cancer patients but quickly discovered that it was also present in controls and that its levels do not change during cancer. However, it has been associated with psoriasis. At this point, we can add the pregnancy zone protein to the list of unknowns among abundant blood proteins. I am sure that many readers can contribute their own anecdotes about exciting discoveries that await us in the characterization of the blood proteome, and we do welcome letters to the editor on this subject. In the last Editorial, I expressed concern that there is a general feeling that we already have too many biomarkers, and so we need to take the ones we have and start to validate them. While we do need to react to clinical needs, it is risky to hurry the development of a preliminary set of markers. Another issue is the possible discontinuation of government funding, because of the significant risk that the initial investment will be judged sufficient. Such rush to judgment is foolish when we do not have anything more than an elementary understanding of the biology of plasma and serum. I hope this Editorial promotes some fresh discussion of the challenge of proteomics and its application to early disease diagnosis.
I
Zyomyx
Keith Williams Proteome Systems
Qi-Chang Xia Shanghai Institute of Biochemistry
John R. Yates, III The Scripps Research Institute
© 2004 American Chemical Society
Journal of Proteome Research • Vol. 3, No. 5, 2004
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