E ditor - in - chief
William S. Hancock
editorial
Barnett Institute and Department of Chemistry Northeastern University Boston, MA 02115 617-373-4881; fax 617-373-2855
[email protected] Associate E ditors Joshua LaBaer Harvard Medical School György Marko-Varga AstraZeneca and Lund University Martin McIntosh Fred Hutchinson Cancer Research Center Cons u lting E ditor Jeremy K. Nicholson Imperial College London E ditorial adv isory board Ruedi H. Aebersold ETH Hönggerberg Leigh Anderson Plasma Proteome Institute Rolf Apweiler European Bioinformatics Institute Ronald Beavis Manitoba Centre for Proteomics John J. M. Bergeron McGill University Rainer Bischoff University of Groningen Richard Caprioli Vanderbilt University School of Medicine Thomas E. Fehniger AstraZeneca Catherine Fenselau University of Maryland Daniel Figeys University of Ottawa Sam Hanash Fred Hutchinson Cancer Research Center Stanley Hefta Bristol-Myers Squibb Denis Hochstrasser University of Geneva Michael J. Hubbard University of Melbourne Donald F. Hunt University of Virginia Barry L. Karger Northeastern University Joachim Klose Charité-University Medicine Berlin Matthias Mann Max Planck Institute of Biochemistry David Muddiman North Carolina State University Robert F. Murphy Carnegie Mellon University Gilbert S. Omenn University of Michigan Akhilesh Pandey Johns Hopkins University Aran Paulus Bio-Rad Laboratories Jasna Peter-Katalini´c University of Muenster Peipei Ping University of California, Los Angeles Henry Rodriguez National Cancer Institute Michael Snyder Yale University Clifford H. Spiegelman Texas A&M University Ruth VanBogelen Pfizer Global Research & Development Timothy D. Veenstra SAIC-Frederick, National Cancer Institute Scot R. Weinberger Molecular Sensing, Inc. Susan T. Weintraub University of Texas Health Science Center John R. Yates, III The Scripps Research Institute
© 2007 American Chemical Society
Brain Research: Will History Repeat Itself in Proteomics?
P
roteomics is a state-of-the-art research field that is growing at a rate of 50% per year as estimated by the number of manuscripts submitted to proteomics journals. However, the knowledge gain that results from big science such as proteomics sometimes is thought of as suboptimal. Reproducibility is a key issue. Biobanks with well-characterized tissues and methods that include validation tools are crucial. The analysis of nonstandardized samples from incongruent patient cohorts and the use of imbalanced statistics lead to the publication of false-positive and false-negative results. In terms of time and funding, these false findings hamper follow-up studies that rely on these experiments. A carefully designed strategy for sample collection, the application of proper statistics to the data, and the validation of results with independent methods are mandatory. This is especially true for neuroscience because of the complex and highly valuable samples that are derived from human specimens. Brain samples stored in tissue banks often originate from patients who had several illnesses and who took many medications throughout their lifetimes. Without protective treatment, these samples can show substantial protein degradation several hours postmortem. These findings have been addressed already by other research fields, such as geno mics. Unfortunately, it seems that history will repeat itself in every new research area. The same mistakes are being made again by researchers who ignore basic analytical and bioinformatics requirements. So what should we do, especially when we consider the increasing rates of elderly people with dementia? The mission seems clear: learn from previous mistakes. 1. Support standardization and harmonization efforts—for example, HUPO and its initiatives, such as the Proteomics Standards Initiative and the Human Brain Proteome Project, or the EU-funded project Proteomics Data Collection (ProDaC)—by using the organizations’ standard recommendations. 2. Identify or initiate biobanks that supply comparable samples treated identically. 3. Use targeted analysis strategies, for example, microdissection of brain areas of interest before the study. The strategies can be common (but sound) or innovative, for example, the correlation of neurodegenerative diseases with lifestyle effects. 4. Combine all proteomics/genomics/bioinformatics methods available and validate results with highly specific methods. Already, proteomics is making great strides: HUPO and ProDaC have advisory boards, hold frequent meetings and workshops, and develop standards. Central collection of data from proteomics experiments and from experiments in other scientific fields is essential for future and ongoing work, such as systems biology projects. A critical data pool that allows for the analysis of the processes in a complex tissue such as the brain can be formed only by comparing quantitative results of complementary techniques and by assessing several repeated data sets. The availability of validation tools, especially highly specific, well-characterized antibodies, must be improved. Here, the EU-funded project Proteome Binders as well as the HUPO Human Antibody Initiative are bringing this urgent task to the forefront. It took 10 years for researchers in the field of genomics to establish a sophisticated platform for the scientific community. For the even more complex (brain) proteomics, this might take longer but will, in the end, definitely be worth the endeavor, because proteomics is one of the most powerful new fields in life sciences still waiting for full exploitation of its potential. MICHAEL HAMACHER, CHRISTIAN STEPHAN, KATRIN MARCUS, and HELMUT MEYER Ruhr University Bochum (Germany)
Journal of Proteome Research • Vol. 6, No. 12, 2007 4539
