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Human Plasma Proteome Project

With its central role in human physiology, blood provides a unique window into human health and disease. As it circulates the human body, blood may contain markers indicating changes from homeostasis. Compared to tissue samples, the ease of acquisition and handling makes blood derived specimen an attractive source for building repositories, such as in large scale biobanks. Nevertheless, analyzing blood-derived plasma or serum still poses one of the major challenges for proteomics in terms of sensitivity and analytical depth. With growing numbers of plasma samples being systematically collected, stored, and accessible through biobanks, the HPPP initiative aims to collect the advances in plasma protein analysis from different technologies, diseases, and concepts. This includes bringing together different contributions to the field in mass spectrometry and affinity-based assays and provide a platform to discuss success stories, technological possibilities, viewpoints and perspectives on how plasma proteomics has and will continue to advance.

Current lines of work:

  • Definition of the content of the plasma proteome by characterization in health and disease.
  • To collect protein levels obtained in different studies and with different technologies
  • To develop targeted standardized methods for the quantification of clinically relevant proteins.
  • To identify technologies and advances in plasma analysis
  • To identify requirements in study design, patient and sample related information. 

Overview of Project

The HPPP was initiated in 2002 with a series of planning workshops. During 2003-2005, the HPPP prepared and distributed reference specimens of human serum and EDTA-, citrate-, and heparin-plasma to 55 participating laboratories worldwide. The HPPP stimulated access to emerging technologies and generated substantial datasets and integrated databases for proteins detectable and identifiable in human plasma and serum. Experimental protocols used combinations of depletion, fractionation, mass spectrometry, and immunoassay methods linked via search engines and annotation groups to gene and protein databases. We created a new human plasma proteome database. We concluded that EDTA-plasma is the preferred specimen for studies of plasma or serum from human blood.

A special issue of PROTEOMICS in August 2005 presented 28 articles from the HPPP—both collaborative articles and ancillary analyses stimulated by a special small grants program. Collaborating laboratories and working groups of this Pilot Phase of the HPPP addressed (a) specimen stability and protein concentrations; (b) protein identifications from 18 MS/MS datasets, including subproteome analyses; (c) independent analyses from raw MS/MS spectra; (d) search engine performance; (e) biological annotations and insights; (f) antibody arrays; and (g) direct MS/SELDI analyses. A Core Dataset of proteins identified based on two or more peptides had 3020 protein IDs characterized with Gene Ontology, InterPro, Novartis Atlas, Online Mendelian Inheritance in Man, and immunoassay-based concentration determinations. Using different criteria, several subsets of the Core Dataset were described. The work was also published as a book by Wiley “Exploring the Human Plasma Proteome” in 2006.

In Phase II, the HPPP has grown with the contribution of additional large datasets and standardized analysis using TransProteomiec Pipeline to create the current version of the Human Plasma PeptideAtlas (see Farrah et al, Mol Cell Proteomics, 2011). Preliminary data from Peptide Atlas cross-analyses with the urine, kidney, and liver proteome datasets from the HUPO KHUPP and HLPP initiatives were presented at the Sydney HUPO Congress in 2010. Data from the HBPP are under cross-analysis. The tiered scheme called Cedar, published by Farrah et al (2011), has 1929 protein IDs in the canonical set defined by stringent false-discovery rates (1% at the protein level and 0.16% at the peptide level) and reduction of redundant matches. We recommend this scheme for other proteome analyses and cross-analyses.

Collaborations with other Initiatives:

  • This project is committed to interact with HLPP and HBPP in order to assure analyses of serum and/or plasma side-by-side with analyses of tissue specimens, as forerunner to establishing accessible biomarker assays for tissue proteins of interest in various disease states.
  • Bioinformatics and data analysis and storage issues are done in collaboration with Hermjakob and Apweiler from the Proteomics Standards Initiative.
  • An interaction with the Human Antibody Initiative (HAI) is underway so that any antibodies generated can be added to the HAI database.

Key documents related to activities:

Papers:

  • Huang Z, Ma L, Huang C, Li Q, Nice EC., Proteomic profiling of human plasma for cancer biomarker discovery, Proteomics. 2016 Aug 23. doi: 10.1002/pmic.201600240
  • Geyer PE, Kulak NA, Pichler G, Holdt LM, Teupser D, Mann M., Plasma Proteome Profiling to Assess Human Health and Disease, Cell Syst. 2016 Mar 23;2(3):185-95. doi: 10.1016/j.cels.2016.02.015
  • Keshishian H, Burgess MW, Gillette MA, Mertins P, Clauser KR, Mani DR, Kuhn EW, Farrell LA, Gerszten RE, Carr SA, Multiplexed, Quantitative Workflow for Sensitive Biomarker Discovery in Plasma Yields Novel Candidates for Early Myocardial Injury, Mol Cell Proteomics. 2015 Sep;14(9):2375-93. doi: 10.1074/mcp.M114.046813

Related links:

www.bioinformatics.med.umich.edu/hupo/ppp

www.ebi.ac.uk/pride

Leadership:

Jochen Schwenk, Chair

Eric Deutsch, Co-Chair

For more information or participation opportunities please contact office(at)hupo.org.



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