P R O T EO M ICS P R O J EC T S
HKUPP becomes a full-fledged initiative of its own Following in the footsteps of HUPO’s Cardiovascular Initiative (CVI; J. Proteome Res. 2007, 6, 1242), the Human Kidney and Urine Proteome Project (HKUPP; www.hkupp.org) also has left the Disease Biomarker Initiative (DBI) and struck out on its own. According to Tadashi Yamamoto, who is at Niigata University (Japan) and is chair of HKUPP, several groups wanted to form HUPO initiatives in 2005. He says that HUPO responded by bringing five of them (including HKUPP) under one umbrella, called DBI. Echoing CVI’s reasons for leaving, Yamamoto explains that HKUPP members “do not want to restrict our scientific fields just to the discovery of biomarkers of kidney disease.” Therefore, HKUPP made the move to become a freestanding HUPO initiative at the HUPO council meeting during the HUPO Sixth Annual World Congress in Seoul last fall. Kidney diseases have been studied for decades, but Yamamoto points out that the causes and molecular interactions involved in these diseases still are not well understood. To figure out how kidney disease processes work, his team members performed transcriptome studies, but they soon realized that the proteome could provide even more information about normal and disease states. “So, we discussed this with several of our colleagues and agreed to do a proteomics analysis in an international collaboration,” he recalls. This collaboration to study kidney functions and disease mechanisms became HKUPP. To accomplish their goals, HKUPP members work on subprojects. One of these is an effort to generate guidelines on urine collection, storage, and processing. Such guidelines would help researchers compare results across laboratories and provide best practices for newcomers. Yamamoto explains that composition of urine is much more variable than that of plasma. Urine samples differ from person to person and even throughout the day for one individual, and they can be rapidly affected by the environment and other factors. For example, just drinking a lot of water or eating salty food can drastically alter the concentration and composition of urine. Also, nearly every laboratory
has its own method for the collection and handling of urine samples. Some researchers collect the first urine of the day, whereas others collect the second morning urine, random daytime samples, or many samples throughout a 24 hour period. Specimens can be spun to remove debris, stored in a refrigerator or a freezer, or depleted of high-abundance proteins such as albumin. These and other sources of variability were the focus of roundtable discussions at the Seoul HUPO meeting and at the Second HKUPP Workshop, which was held during the American Society of Nephrology 40th Annual Meeting in San Francisco. HKUPP member Visith Thongboonkerd, who is at Siriraj Hospital and Mahidol University (Thailand), is leading the guidelines subproject. He handed out questionnaires to members to see what methods they suggest. Once the responses are collected, he will sort through them and other data sources to generate a summary of recommendations. Already, members are close to reaching consensus on a few topics. However, more contentious issues, such as whether protease inhibitors should be added to urine samples, will require much more input. Thongboonkerd says that HKUPP plans to submit a summary of the guidelines for publication later this year. The other subprojects involve the identification of proteins in the kidney and urine proteomes and the construction of databases to store this information. As HKUPP member Peter Yuen of the U.S. National Institute of Diabetes and Digestive and Kidney Diseases at
What is DBI?
Although DBI was first described as an umbrella organization for five groups (see the official newsletter, HUPOST, December 2005), its membership now varies. DBI doesn’t have a website listed on the HUPO homepage, and the group did not have a dedicated initiative session at the Seoul HUPO meeting. So, what is DBI? According to Martin McIntosh, who is active in DBI projects and is at the Fred Hutchinson Cancer Research Center, “I think the Biomarker Initiative should be viewed as a way to foster collaborations on aspects specific to
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the National Institutes of Health points out, most of the proteomics work is being conducted on urine samples, but a few groups are forging ahead on proteomics studies of biopsies and isolated glomeruli from animals. Another subproject involves the connection of the HKUPP databases to those of other initiatives. Yamamoto says, “The most important thing, postgenome, is that we need to provide a human proteome database in general, similar to [that of] the human genome database.” Scientists from the European Bioinformatics Institute (U.K.) will help HKUPP members make their databases more compatible with those of the other groups as a step toward a global human proteome repository. Down the road, HKUPP members plan to characterize and compare urine proteomes of people of different ages, genders, and ethnic backgrounds and to study the effects of exercise and nutrition on the proteomes, says Yamamoto. With many kidney diseases, increased protein levels are observed in urine (proteinuric urine), and this feature makes urine more difficult to analyze with proteomics methods. Therefore, members may develop guidelines for dealing specifically with proteinuric urine samples. Interested researchers are still welcome. To join, email Yamamoto at
[email protected] or attend one of the HKUPP meetings. To share urine collection and processing data, contact Thongboonkerd by email at
[email protected]. —Katie Cottingham molecular markers, including diagnosis, prognosis, targets for therapy, and predictions, and which naturally will be activities that function across different organ sites.” He says that DBI was not formed to replace organ-specific initiatives, such as the Human Liver Proteome Project, but was organized to give researchers who were interested in focusing on biomarker discovery a slightly more formal way to strike up collaborations. As such, DBI is a fluid initiative that HUPO scientists can consult or participate in while they retain membership in one of the more organ-based initiatives, he says.
