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HUPO Plasma Proteome Project Faces Path Littered With Obstacles, Researchers Say

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By announcing at a recent conference that HUPO would attempt to lead a coalition of researchers in a study of all the proteins in human serum, HUPO President Sam Hanash has placed his bet that the proteomics community will rally around an initiative with both broad appeal and clinical relevance. A plasma proteome project, he said, could serve as a launching pad for future initiatives and as a test case for how well researchers can submit themselves to a common cause.

Test case is right. Many scientists involved in proteomics agree in theory with Hanash’s objectives — they would like to see good quality data on the plasma proteome assembled in a publicly accessible database — but in order for the project to succeed, they add, it must jump over a series of high hurdles.

On one level, a HUPO project to identify and measure the expression of proteins in plasma under various conditions could potentially overlap with work already underway in the private sector. Duplicating the efforts of proteomics heavyweights such as GeneProt and Large Scale Biology, the argument goes, is not the wisest use of public money.

“Serum is an obvious choice: not surprisingly it’s the same choice made by ourselves, GeneProt, Celera [and others],” said Leigh Anderson, LSBC’s chief scientific officer. “Clearly the better part of the data obtained by the proteomics companies is unlikely to show up through HUPO in the public domain, and thus much of a HUPO serum project could turn out to be duplicative.”

The other side of the argument, of course, is that duplication is a necessary evil, given that the objective is to provide public researchers with freely accessible data. Furthermore, a HUPO-sponsored project is unlikely to threaten the value of plasma proteome studies conducted in the private sector, supporters said, because of the wide discrepancy in resources available to the two parties.

“What GeneProt is offering is lead-time,” said Josh LaBaer, of the Harvard Institute for Proteomics, at a planning meeting held prior to the Jan. 9-11 HUPO conference in San Diego. A HUPO project might compete with a company such as GeneProt by providing an alternative free source of data, he added, but certainly not as quickly.

 

How Useful a Catalog?

 

On a more fundamental level, scientists in the field also raised questions about the ability of a loosely-bound collection of studies on the plasma proteome to serve as a standard for future experiments. Often the most valuable studies are driven by a hypothesis related to a specific biological question, and a general catalog of proteins found in serum would not serve as a useful control, said Matthias Mann, chief proteomics officer of MDS Proteomics and a researcher at the University of Southern Denmark.

“Technically it’s a low IQ experiment,” added John Yates, a protein mass spectrometrist at the Scripps Research Institute. “It’s not hypothesis-driven, and it’s only marginally discovery-driven.” For the HUPO project to be valid for future experiments, he said, the data would have to contain absolute, rather than relative, measurements of protein expression levels.

In their defense, HUPO supporters said that the value of a collaborative project lies inherently in the range of experimental conditions underlying the common pool of data. With the help of as-yet-undefined data standards, they said, bringing together a collection of studies comparing a variety of disease and normal states in plasma is bound to be beneficial to the community at-large.

“The useful thing to have — even more than in the microarray and genomics fields — is to bring the hundreds of groups doing small projects, and [find a way] to judge how all the data are related,” agreed Mann.

Perhaps the biggest question mark surrounding the proposed project is where to find funding. NIH has made preliminary overtures by agreeing to host brainstorming sessions on its campus in Bethesda, Md., where HUPO in April will solicit feedback from proteomics researchers, but NIH has yet to pledge the kind of support afforded the Human Genome Project.

Nor does HUPO itself plan to control the purse strings, assuming it could raise the necessary funds from public and private sources to fuel the plasma project. Instead, the organization wants to act as a standard-bearer, generating the concepts and initiatives but steering clear of financial matters that affect individual researchers.

“The real question — where the rubber meets the road — is, Can they get funding for it?” said Yates. “I don’t know if there’s support for a large scale project because the technology still needs to be developed.”

— JSM