Seattle, United States — The Institute for Systems Biology (ISB) in Seattle, Washington, and the Swiss Federal Institute of Technology (ETH Zurich) in Zurich, Switzerland announced today at the 9th Annual World Conference of the Human Proteome Organization (HUPO) in Sydney, Australia, that they have completed the first phase of generating a complete map of the human proteome by mass spectrometry. These data will be made accessible to the research community through the ISB/ETH SRMAtlas database (www.srmatlas.org) as part of the ISB/ETH PeptideAtlas (www.peptideatlas.org) project.

The groups report that they have generated “gold standard” reference mass spectrometry spectra for each of the 20,300 genes currently annotated as protein-encoding in the human genome. This reference map will enable researchers to detect and quantify any human protein in any biological sample using targeted mass spectrometry techniques such as selected reaction monitoring (SRM) and to analyze data generated by the classical discovery mass spectrometry techniques faster and more reliably. Associate Professor Robert Moritz, Ph.D. (ISB), Professor Leroy Hood, M.D., Ph.D. (ISB) and Professor Ruedi Aebersold, Ph.D. (ETH) with their teams and partners have created over 150,000 SRM (selective reaction monitoring) assays, including one for each of at least 5 proteotypic (protein-specific) peptides per protein. In addition, they have created SRM assays to specifically target all membrane proteins and almost all proteins potentially containing a carbohydrate attached through an N-glycosylation sites. They have also extended the assays to target the majority of amino acid changing mutations arising from single letter changes in the DNA code of genes (single nucleotide polymorphisms or SNP’s) represented in the human population at frequencies greater than 30%. Collectively, these assays constitute the most comprehensive publicly accessible resource to investigate the human proteome to date.

One of the most fundamental contributions of the human genome project was making all human genes available to all biologists; similarly, this human proteome project will eventually make all proteins available to all biologists.

The team at ISB headed by Robert Moritz has developed the workflow in collaboration with Ruedi Aebersold and his team at ETH. Ruedi Aebersold, a co-founder of ISB and a professor of systems biology at the Swiss Federal Institute of Technology (ETH-Zurich) is one of the co-PIs on the SRM atlas project along with Lee Hood, the president of ISB. Dr. Aebersold has pioneered the generation of public resources supporting the mass spectrometric investigation of the human proteome.

The project was supported at ISB by the National Human Genome Research Institute of the National Institutes of Health which provided $2.7 million in direct funding under the American Recovery and Reinvestment Act of 2009. The project at ETH was supported by ERC Advanced Grant Proteomics v3.o Grant n# 233226 Funding for 5 years Total EUR 2.4 million.

The project was also supported by two leading technology companies, Agilent Technologies and AB/SCIEX, who provided instrument support to ISB and ETH Zurich, respectively, peptide supply companies Thermo-Fisher and JPT and by a biological supply company, OriGene, which is providing purified human proteins.

The complete human proteome map and S/MRM atlas will provide researchers with a comprehensive set of information and assays to detect and quantify any human protein in any biological sample. This important development will greatly increase the reproducibility and reliability of proteomics research, therefore significantly accelerating both basic and translational research. By mining the ISB Peptide Atlas of the 10,000 known human proteins created by Prof. Aebersold in 2003, and supplementing this information with peptide prediction algorithms for the remaining human proteins developed through bioinformatic analysis by ISB researchers and their collaborators, the team has been able to derive the best proteotypic peptides to use for SRM where no physical data exists. The total set includes at least five peptides for each protein. In addition, tools which will allow a researcher to choose the best peptide transitions to uniquely identify those peptides in a complex mixture.

The Atlas will be released through the SRMAtlas website and all information from the project will be open source.