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Content archived on 2024-06-18

Proteomics v3.0: Development, Implementation and Dissemination of a Third Generation Proteomics Technology

Final Report Summary - PROTEOMICS V3.0 (Proteomics v3.0: Development, Implementation and Dissemination of a Third Generation Proteomics Technology)

Proteomics is the field of science that aims at comprehensively analyzing the ensemble of proteins expressed by a cell or tissue. Because proteins catalyze and control essentially any biological process, proteomics is essential for virtually any branch of life science research from the study of basic processes to translational research for the benefit of patients.

The proteome of a cell or tissue is constantly changing along with the acute state of the tissues. For example, the proteome of a tumor cell is considerably different from the proteome of a healthy cell of the same tissue from the same person. In addition, the proteome consists of tens of thousands of different proteins and is therefore challenging to analyze. Overall, the investigation of the proteome has been limited by the available measurement methods. The ERC project Proteomics v3.0 pursued the goal of making all the proteins of a proteome reproducibly and quantitatively measurable by most laboratories,.

Before this project, the complexity of the proteome confounded even the most powerful measurement methods. It was the premise of the project a that fundamentally different approach was required to reach the project’s goals. This approach was targeting mass spectrometry that explores the proteome using a complete proteome map as prior information in the form of one or several specific assays for the definitive measurement of each protein of a proteome. The assays developed by the project are libraries of fragment ion spectra for a number of peptides, each one uniquely identifying a particular protein of a proteome.

At the time of its completion the project has significantly transformed the landscape of proteomics research. This is supported by the fact that the journal Nature Methods elected targeted proteomics, the subject of the project Proteomics v3.0 as the method of the year 2012. This success is based on several significant technical achievements that collectively integrate into a complete analytical technology. Specifically, these include: i) The development of complete, community accessible assay libraries for all proteins of the species Saccharomyces cerevisiae, Micobacterium tuberculosum and Homo sapiens. In addition, for the human proteome assays were also developed for a large fraction of N-glycosylated proteins, ii) open access software tools were developed to accurately quantify sets of proteins across large sample cohorts, iii) a new measurement technology SWATH-MS was developed that supports the quantification of the proteome at unprecedented accuracy and reproducibility and iv) initial applications of the targeted proteomics technology developed by the project have uncovered new biological and clinical findings.

Overall, the project has achieved all its technical goals, exceeded many of the stated aims and has catalyzed a significant change in the proteomics community towards the generation of high quality large scale datasets derived from large sample cohorts. The technology is now well established, supported by the resources generated by the project and we therefore expect that the long term transforming effect envisaged by the project will carry forward into the future for a long time to come.