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ISB and OriGene to Collaborate on MRM Database for 5,000 Human Proteins

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By Adam Bonislawski

OriGene Technologies and the Institute for Systems Biology announced plans this week to build a proteotypic PeptideAtlas and SRM/MRM mass spectrometry standard database for 5,000 human proteins.

The collaboration, which aims to characterize the tryptic peptides of the 5,000 proteins in order to generate mass spectroscopy assays for them, brings together ISB's mass spectroscopy expertise and OriGene's extensive human protein collection.

The project builds upon another MRM atlas project in which ISB is working with Agilent Technologies to map peptides for each of the 20,000 to 25,000 protein-coding genes in the human proteome [PM 10/23/2009]. That project, which was announced last October and received $2.7 million in funding from the National Human Genome Research Institute under the American Recovery and Reinvestment Act of 2009, should be completed by September of 2011, according to Robert Moritz, director of proteomics at ISB.

The collaboration with OriGene will allow ISB to expand its work on this atlas by giving it access to one of the world's largest collections of full-length human proteins. While the NHGRI-funded project is using synthesized peptides, OriGene's proteins, produced via expression systems inserted into human embryonic kidney 293 cells, will provide the ISB with peptides that until now it has been unable to work with due to the difficulty of producing them through chemical synthesis.

OriGene declined to comment for this story.

"This will complement the peptide production that we have going on for getting all the proteotypic peptides for every human protein," Moritz told ProteoMonitor. "What we're able to do here with these [OriGene] proteins is complete the sets of data as we go forward with larger sets of peptides beyond what we can do with chemical synthesis."

An additional benefit is that OriGene's proteins exhibit post-translational modifications not seen in synthetically created peptides. Working with the OriGene proteins will allow ISB to expand its database of these modifications, particularly, Moritz noted, carbohydrate attachments, which have shown potential as biomarkers for a range of cancers.

Also useful to researchers is the fact that OriGene's proteins can be expressed in heavily labeled media, which will allow for SILAC experiments.

Initially the collaboration will work with the roughly 5,000 proteins that comprise OriGene's human protein library. According to Moritz, however, the company has done trial expression on nearly 12,000 proteins, and, as OriGene puts additional proteins into production, ISB researchers will generate mass spectroscopy assays for them.

"This is just the start," Moritz said. "As they continue to produce [human proteins] we'll continue to analyze them."

He estimated that ISB would be finished analyzing the initial batch of 5,000 proteins by the end of the year.

The collaboration between ISB and OriGene, following the establishment last year of the partnership between ISB and Agilent, represents what Moritz said is a "new style of collaboration where commercial companies look toward leading non-profit organizations to provide avenues for their technology."

The results of the ISB's analysis will be released to the public domain. Nonetheless, the collaboration has potential commercial benefits for OriGene. In addition to producing the proteins themselves, the company is producing matched, monoclonal antibodies for each of them. ISB's mass spec analysis of these proteins could potentially make both lines of product more useful to researchers.

"They will have a full catalog of both protein reagents as well as antibody reagents, and by using this on the mass spectrometer, we're able to increase the use of that technology," Moritz said.

"I think the commercial enthusiasm for this project probably has to do with the fact that [OriGene] is getting free characterization of all [its] products, which is useful, and they're also enabling a much wider variety of researchers to work on the measurement of these proteins — and that obviously will increase the need to get a hold of the protein itself," Leigh Anderson, founder and CEO of the Plasma Proteome Institute, told ProteoMonitor.

Anderson is an early advocate of MRM as a quantitative technology and has developed an MRM-based method called Stable Isotope Standards and Capture by Anti-Peptide Antibodies, or SISCAPA.

Similar benefits could redound to Agilent. As Ken Miller, director of LC-MS marketing for Agilent, told ProteoMonitor when the ISB-Agilent collaboration was announced last year, the company hopes to establish itself "as a standard platform for performing these assays."

"The benefit for those two companies is that OriGene would be the supplier of proteins that anybody would want to use in a quantitative way, and Agilent would be a supplier of instrumentation that anyone could just plug into," Moritz said.

"OriGene's main goal at the moment is to commoditize proteins and protein products much like what has happened with DNA. DNA is such a commodity these days. You just order it from a company — the cost per oligo is on the level of cents to dollars," he said. "That's what they're planning on doing with proteins as well — commoditizing all the human proteins into catalogs and being able to order those reagents from a single catalog."

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