Proteomics Planning Workshop

National Human Genome Research Institute

National Institutes of Health
U.S. Department of Health and Human Services

Workshop Summary

Proteomics Planning Workshop
National Human Genome Research Institute

Natcher Conference Center
National Institutes of Health
Bethesda, Md.

April 25-26, 2002

A workshop was convened by three National Institutes of Health institutes - the National Cancer Institute, the National Institute of General Medical Sciences, and the National Human Genome Research Institute - to review the current status of proteomics and to discuss how these three institutes could most effectively invest in proteomics research. Participants were asked to consider what kinds of proteomic techniques and information would be most useful to address biological and medical questions.

As explicitly defined at the outset of the workshop, proteomics is the study of proteomes, the collections of proteins encoded by genomes. The term 'proteomics' carries with it the connection to genomics and the implication of completeness. It is completeness, and the global view afforded by completeness, that distinguishes proteomics from rapid biochemistry. In fact, proteomics achieves its greatest power in the comparison and analysis of multiple, complete proteomic datasets.

The general goal of proteomics is to monitor the properties of the entire complement of proteins from a given cell or organism, and to determine how these properties change in response to various physiological states, such as signaling ligands, cell cycle, and disease. Much of the discussion in the workshop was on 'focused proteomics,' studies of portions of proteomes, which are undertaken as explorations of new methods or as pilots, often looking at specific tissues, cell types, biological pathways or diseases. Focused proteomics projects may represent a useful way to do limited studies on the way to full proteomics, although they can be informative explorations of specific problems in their own right.

Both short- and long-term goals for proteomics evolved from the discussions of the workshop. A major goal for the short term is to profile, or to take the census of, proteins present in particular cell types. Profiling is approaching reality for cells from some model systems, including numerous microorganisms. Challenges include profiling proteins present at low abundance and membrane proteins, and the proteins of higher cells. Learning the absolute abundance of each protein is the next step, including splice variants of each protein, and all modified forms. With over 200 known types of covalent modifications of proteins, profiling modified proteins presents a formidable challenge. In the short term, examining the protein profiles of diseased cells and comparing them to normal profiles can offer diagnostic and prognostic tools in medicine. Yet another goal of proteomics is to map the protein interactions in each cell type.

In the longer term, a complete interaction map of proteins in human cells will serve as an atlas for the biological and medical explorations of cellular metabolism. Along with this goal, scientists want to know the cellular location of each protein, and how it changes during a protein's lifetime and the cell cycle. The dependence of protein populations on cell cycle, and on perturbations by small molecules (nutrients and drugs) and by protein ligands needs to be catalogued. In the long run, such studies will provide the informational infrastructure for biology and medicine. It is conceivable that in the midterm, proteomic information from both humans and pathogens will provide crucial information for routine medical diagnosis and treatment.

A wider view of proteomics must include the cellular census of lipids, carbohydrates and other metabolites, the subfield of metabolomics. Changes of these populations of small molecules upon perturbations of various sorts, including those of drugs, will provide information crucial to enhanced pharmacology and nutrition.

Classical biomedical research, in which one system is studied thoroughly, can be greatly enhanced by proteomics. Proteomics aids in the discovery of protein function; it helps in understanding specific biological processes such as apoptosis and the cell cycle, and it helps in developing new tools for diagnosis and therapy. The approaches of both the broad view and the single intense view achieve their greatest clarity when both illuminate the other. Focused proteomics offers a middle ground between the intensive, classical view taken by biomedicine and the global proteomic view. This middle ground allows biological systems and clinical protocols to be explored with existing, albeit limited technologies as new technologies are tested.

The workshop developed broad consensus about the following major issues in proteomics:

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Last Reviewed: June 2005