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Molecular & Cellular Proteomics 7:626-627, 2008.
© 2008 by The American Society for Biochemistry and Molecular Biology, Inc.


HUPO Views

Human Disease Glycomics/Proteome Initiative (HGPI)

Naoyuki Taniguchi{ddagger}

From the Department of Disease Glycomics, Institute for Microbial Diseases, Osaka University, Suita Osaka 567-0871, Japan and Disease Glycomics Team, Systems Glycobiology Research Group, Frontier Research System, RIKEN, Wako, Saitama 351-0198, Japan

It is well known that over 50% of all proteins undergo glycosylation, and the characterization of the function of sugar chains (glycans) attached to glycoproteins, glycolipids, and proteoglycans is clearly an important issue in HUPO activity. Structures and functions of glycoproteins have attracted much attention of scientists in various fields of life science and implications of glycan changes in cancer, inflammatory diseases such as influenza, nerve degenerative diseases, muscle degenerative diseases such as muscle dystrophy, and lifestyle-related diseases such as diabetes have been reported. Very recently the white paper was reported from focus groups at the National Institutes of Health workshop (1) held in September 11–13, 2006 (2).

The aim of the Human Disease Glycomics/Proteome Initiative (HGPI) is to define community standards for data presentation in functional glycomics in relation to diseases. The chair is Naoyuki Taniguchi, and James M. Paulson, Claus Willi von der Lieth, Hisashi Narimatsu, and Kazuyuki Nakamura are the vice-chairs. The goal is to facilitate data comparison, exchange, and verification. The HGPI will be comprised of a number of researchers and collaborators throughout the world who are dedicated to fostering and accelerating research progress in disease glycomics by pursuing collaborative and interdisciplinary research. This initiative will connect the other initiatives in HUPO more tightly and will permit the exchange of information of mutual interest. The data and information will be shared with members, non-participating researchers and will be made available for public, academic research, and teaching purposes. In order to avoid diluting efforts by other on-going related activities such as NIH consortium for Functional Glycomics, Japanese Consortium for Glycobiology and Glycotechnology, EurocarbDB etc., this initiative will focus exclusively on disease glycomics using functional glycomics (3).

The goal of HGPI is to develop technologies, to exchange data information, and to provide special reagents and resources related to glycans in disease. Glycomics is mainly based on the characterization of sugar chains, which are not adequately addressed by the characterization of proteins.

Through collaborative research projects, meetings, and web-based interactive activities, the HGPI will serve to promote interactions among investigators in common areas as well as those working in closely related initiatives such as the liver initiative, the brain initiative, and the plasma protein initiative under the auspices of HUPO. The initiative is aimed to characterize the disease-related glycome using two complementary approaches: one is based on functional glycomics and the second on mass spectrometry and to identify disease-related glycomes in blood and urine that represent potentially useful glyco-biomarkers for the early diagnosis, monitoring, and treatment of common diseases such as cancer, inflammation, lifestyle-related diseases, neurodegenerative diseases, and carbohydrate disorders of glycosylation using newly developed, high-sensitive, and high-throughput mass spectrometry. The data obtained by the above groups will be collected and integrated by the glyco-informatics group.

Under HUPO, the HGPI is actively involved in the standardization of mass spectrometry technology for the analysis of sugar chains and the development of biomarkers for disease. The first pilot study among 22 institutions worldwide to analyze standard glycoproteins (human serum IgG and transferring) by experts in the glycomics using mainly mass spectrometry was headed by Yoshinao Wada (Osaka Maternal and Children Research Institute) and was reported last year (4) and now second pilot study for O-glycan analyses using IgA1 as the standard samples is ongoing, headed by Anne Dell (Imperial College, UK). The next pilot study on biomarker discovery is being planned by Hisashi Narimatsu (a new chair of HGPI) and others.

In terms of international collaborations, HUPO plays a key role in the organization of proteomic research but not in glycomics. In 2005, HGPI hosted a joint meeting with German scientists including the EUROCarbDB group headed by the late Willi von der Lieth in Florence supported by JSPS designated as the core-to-core program funded by JSPS (Japan Society for Promotion of Science and the 21st Century Center of Excellence (COE) program, Osaka university headed by Naoyuki Taniguchi), and in 2006 HGPI again co-organized a meeting with Consortium for Functional Glycomics headed by James Paulson (Scripps Research Institute) entitled "Frontiers in Glycomics: Bioinformatics and Biomarkers in Disease" at the main campus of the National Institute of Health, Bethesda (organizers are James Paulson, Pamela Marino, Sasisekharan R., and N. Taniguchi N) (2). At this meeting, the focus group summarized an NIH white paper (1) and emphasized the importance of bioinformatics and biomarker discovery using the glycomics approach. The reason for this is that most of the cancer biomarker available are glycoproteins and glycolipids, but the measurement of these glycoproteins such as AFP, CEA, PSA etc. are based on the enzyme-linked immunosorbent assay (ELISA) using specific antibodies against the protein moiety. However, very recently fucosylated {alpha}-fetoprotein was approved by Food and Drug Administration as one of the best markers for primary hepatocellular carcinoma because the measurement of AFP by monoclonal antibody was not valuable for the differential diagnosis of the liver cirrhosis and primary hepatoma. On the other hand, fucosylated AFP provides a unique marker for this purpose. The other candidate for the pancreatic cancer is fucosylated haptoglobin. As an outcome of this meeting, the National Cancer Institute (NCI), a part of the National Institutes of Health (NIH), is funding a new $15.5 million, five-year initiative to discover, develop, and clinically validate cancer biomarkers by targeting the carbohydrate (glycan) part of a molecule.


    ACKNOWLEDGMENTS
 
This article is dedicated to the late Professor Dr. Claus-Willi von der Lieth who made great contribution to the HGPI and NIH white paper Report. The HGPI was supported by the 21st Century Center of Excellence Program, Osaka University, and core-to-core program (for N. T.) by Japan Society for Promotion of Sciences.


   FOOTNOTES
 
{ddagger} To whom correspondence should be addressed: Dept. of Disease Glycomics, Institute for Microbial Diseases, Osaka University and Disease Glycomics Team, Systems Glycobiology Research Group, Frontier Research System, RIKEN, Wako, Saitama 351-0198, Japan. Tel./Fax: 81-6-6879-4137. E-mail: tani52{at}wd5.so-net.ne.jp


    References
 TOP
 References
 

  1. Packer, N. H., von der Leith, C. W., Aoki-Kinoshita, K. F., Lebrilla, C. B., Paulson, J. C., Raman, R., Rudd, P., Sasisekharan, R., Taniguchi, N., and York, W. S. (2008) in Frontiers in Glycomics: Bioinformatics and Biomarkers in Disease. An NIH White Paper Prepared from Discussions by the Focus Groups at a Workshop on the NIH Campus, Bethesda, MD (September 11–13, 2006) Proteomics 8, 8 –20[CrossRef][Medline]

  2. Taniguchi, N., and Paulson, J. (2007) in Frontiers in Glycomics: Bioinformatics and Biomarkers in Disease. Natcher Conference Center, NIH Campus, Bethesda, MD (September 11–13, 2006) Proteomics 13, 1360 –1363 (Epub ahead of print)

  3. Taniguchi, N., Miyoshi, E., Gu, J., Honke, K., and Matsumoto, A. (2006) Curr. Opin. Struct. Biol. 16, 561 –566[CrossRef][Medline]

  4. Wada, Y., Azadi, P., Costello, C. E., Dell, A., Dwek, R. A., Geyer, H., Geyer, R., Kakehi, K., Karlsson, N. G., Kato, K., Kawasaki, N., Khoo, K. H., Kim, S., Kondo, A., Lattova, E., Mechref, Y., Miyoshi, E., Nakamura, K., Narimatsu, H., Novotny, M. V., Packer, N. H., Perreault, H., Peter-Katalinic, J., Pohlentz, G., Reinhold, V. N., Rudd, P. M., Suzuki, A., Taniguchi, N. (2007) Glycobiology (Epub) 17, 411 –422 (Erratum (2007) Glycobiology 17, 10G)[Abstract/Free Full Text]


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