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HUPO's Chromosome-Centric Protein-Mapping Initiative Draws Researcher, Mass-Spec Vendor Support

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By Adam Bonislawski

Momentum is building for the Human Proteome Organization's "adopt-a-chromosome" initiative, with nine chromosomes having now been claimed by research groups, and mass-spectrometry vendors, including Agilent Technologies, participating in the effort.

Launched in September 2010 at the organization's annual meeting, the project calls for participating countries to take one of the 23 human chromosomes and characterize one representative protein for each gene located on the chromosome.

Researchers will sequence each protein; identify proteotypic peptides and antibodies that can be used to isolate it; and investigate its roles in various disease states.

According to Young-Ki Paik, director of the Yonsei Proteome Research Center in Seoul, Korea, the chromosome-centric approach represents an attempt to provide HUPO's various protein mapping efforts with some sort of defined end point.

"HUPO has been doing a lot of proteome initiatives," said Paik, who with Northeastern University's Bill Hancock is a co-leader of the initiative. "But there has been no end point that we can define. We need a starting point and an end point, and the best [way] to do that is to go according to chromosome number, like the Human Genome Project."

The organizers also wanted "to have an international coalition" behind the effort, and by apportioning the work by chromosome number "we can assign them to each country according to their interests," Paik told ProteoMonitor.

For instance, he noted, researchers in Iran have selected the Y chromosome because of that country's declining birth rate. Japan picked chromosome 3 in part because of its association with lung cancer, a major research interest in that country. On a somewhat less-serious note, Chinese researchers signed up for chromosome 8 because 8 is a lucky number in Chinese culture.

Earlier this month, Swedish researchers, led by Lund University professor and AstraZeneca principal scientist Gyorgy Marko-Varga, announced that they would be taking on chromosome 19, which contains proteins linked to prostate cancer, one of Marko-Varga's research interests. Beside the Lund University scientists, this team will include participants at sites in Norway, Germany, Spain, India, and China.

According to Paik, the initiative, which is expected to take roughly 10 years to complete, will proceed in three stages. The first will consist of assigning all 23 chromosomes – which he said he believe can be completed in a year – and lining up funding, instrumentation, and samples to support the work.

The second phase will focus on identifying the proteins associated with each gene, and generating sequence data that can be used to develop SRM assays and affinity reagents for them.

In the third phase researchers will aim to apply the work of the first two stages to the study of specific disease states.

In practice, however, the protein-mapping efforts and the disease research will likely proceed somewhat in parallel, Paik said. On this point he noted that the disease work would be important for drawing support and funding to the initiative, and that if it were put off entirely until the final stage the project would likely stall.

In terms of industry support, he said he hoped to line up a major mass-spectrometry vendor as the project's first commercial partner, and that companies including Thermo Fisher Scientific and AB Sciex have shown "very strong interest."

AB Sciex, in fact, is the corporate sponsor for HUPO's Human Proteome Project working group workshop, to be held in Busan, South Korea, on March 30, during the KHUPO 11th International Proteomics Conference.

There, Paik said, several teams will present progress reports on their chromosome work, and the group will seek to establish guidelines for quality-control procedures, sample procurement, data reporting. They will also discuss more formal criteria for how chromosomes should be assigned.

Agilent Technologies spokesperson Stuart Matlow told ProteoMonitor that the company would also be participating in the project. He declined to elaborate, but said that an Agilent representative would be presenting at a meeting of the group next week in Toronto.

The initiative's second industry-support option would be lining up backing from a major pharmaceutical firm, Paik said.

The project, with its goals of identifying proteotypic peptides for use in SRM mass-spec assays and developing affinity reagents, dovetails with several other ongoing proteomics initiatives. Most notable of these are the SRMatlas, which is under development at the Institute of Systems Biology and the Swiss Federal Institute of Technology, and the Human Protein Atlas, which is being constructed by Mathias Uhlen, professor of microbiology at Stockholm's Royal Institute of Technology.

At HUPO's 2010 meeting last September, the ISB and ETH researchers presented the first draft of their SRMatlas, which contains more than 170,000 single-reaction monitoring assays – one each for at least five proteotypic peptides for each of the 20,300 human genes currently annotated as protein-encoding (PM 09/24/2010).

In November, Uhlen released the seventh version of the Human Protein Atlas database, which provides localization and expression data on 10,000 human proteins including 10 million high-resolution immunohistochemistry images (PM 11/19/2010).

Acknowledging the overlap between these projects and the chromosome-centric effort, Paik said that one of the goals of the initiative is to "put [the existing databases] together in the context of chromosome number," which, he suggested, could help tie them to disease states and other underlying biology.

Marko-Varga said that his group is currently in discussions with ETH scientist Ruedi Aebersold – one of the leaders of the SRMatlas project.

"He's done a lot of work already, and we don't want to repeat it," he said, "but we want to actually build onto [the SRMatlas work] disease knowledge and disease understanding."

Key to this portion of the project will be obtaining high-quality, well-characterized samples, Marko-Varga said.

"I've worked in the pharmaceutical industry for a long time doing this, and the quality of the samples that you measure is really important," he said. "If you have [well-characterized samples], that's of enormous value because then you can make conclusions and correlations."

Currently, Marko-Varga added, his team is negotiating with AstraZeneca for access to biobanked samples from lung cancer and cardiovascular disease patients.

"We have more than 50 scientists [working on] chromosome 19, so it's quite a lot of resources on hand," he said. "But having said that, this is an enormous challenge. It's not something you fix over a coffee break."


Have topics you'd like to see covered in ProteoMonitor? Contact the editor at abonislawski [at] genomeweb [.] com.

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