Plasma Proteome Project
Overview of Project
The aims of the HUPO Human Plasma Proteome Project (HPPP) are:
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.
- 1. To stimulate large-scale analyses of human plasma and serum specimens and open sharing of results.
- 2. To demonstrate and advance uses of PeptideAtlas and ProteomeXchange.
- 3. To compare findings for the plasma proteome with other biofluid and organ proteomes, using PeptideAtlas.
- 4. To lay a foundation for the biology- and disease-driven component of the emerging HUPO Human Proteome Project (B/D-HPP).
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
- 2011 Farrah et al, Mol Cell Proteomics publication about advanced analyses for the Plasma Peptide Atlas
- 2011 Omenn-Baker-Aebersold Proteomics publication about the 2009 and 2010 HPPP workshops
- 2011 HPPP Report to the HUPO Council
- 2011 Legrain et al publication in Mol Cell Proteomics about the status and prospects for the Human Proteome Project
- 2010 Report to the HUPO Council from the Plasma Proteome Initiative
- 2009 Omenn-Aebersold-Paik Proteomics publication about the 2008 Amsterdam Workshop
- July 2008 Report
- ProteomExchange data submission strategy final
- HUPO Plasma Proteome Project Workshop Agenda - October 7, 2007, Seoul
- September 2007 Report on HUPO Plasma Proteome Project to the initiatives
- Overview of the HUPO Plasma Proteome Project: Results
from the pilot phase published in Proteomics Aug 2005 special issue - Cover page
- Full list of the 28 publications in Proteomics August 2005
- U.S. HUPO Meeting plenary presentation March 2005
- HUPO PPP Update Report
- HUPO PPP pilot Phase: Montreal Workshop Oct 2003
- HUPO PPP Workshop in Bethesda, July 16-17 2003
- Data Capture and Data Analysis
- David States errors and uncertainty in Proteomics
- Pilot studies with reference specimens
- HUPO Plasma Proteome Project
- HUPO/NCI Early Detection Research Network Plasma Proteome Project Workshop