Plasma Proteome Project
Overview of Project
During 2003-2005, the PPP prepared and distributed reference specimens of human serum and plasma to 55 participating laboratories worldwide, stimulated access to emerging technologies, and generated substantial datasets and integrated databases for proteins detectable and identifiable in human serum and plasma. 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 and have developed recommendations for use in future studies with plasma and serum.
Collaborating laboratories and working groups of the PPP Pilot Phase 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. MS/MS datasets had 15710 different International Protein Index (IPI) protein IDs; the PPP integration algorithm applied to multiple matches of peptides sequences yielded 9504 IPI proteins identified with one or more peptides and 3020 proteins identified based on two or more peptides (the Core Dataset). These proteins have been characterized with Gene Ontology, InterPro, Novartis Atlas, Online Mendelian Inheritance in Man, and immunoassay-based concentration determinations. The database permits examination of many other subsets, such as 1274 proteins identified with three or more peptides. Reverse protein to DNA matching identified proteins for 118 previously unidentified ORFs.
The findings from the collaborative project and from lab-specific ancillary projects are published in a special issue of Proteomics, "Exploring the Human Plasma Proteome", August 2005, which was presented to all registrants at the HUPO 4th World Congress on Proteomics in Munich.
The long term goals of this project are:
- Comprehensive analysis of plasma and serum protein constituents in people
- Identification of biological sources of variation within individuals over time, with validation of biomarkers
- Physiological: age, sex/menstrual cycle, exercise
- Pathological: selected diseases/special cohorts
- Pharmacological: common medications
- Determination of the extent of variation across populations and within populations
Next phases of the PPP are under discussion. They may include (a) consensus-building and new studies to generate standardized operating procedures; (b) continuing development and analysis of datasets arising from HUPO initiatives and other published studies; (c) facilitation and possibly organization of major disease-related studies of candidate biomarkers for earlier diagnosis, better stratification of newly diagnosed patients, pathways-based monitoring of targeted therapies, and design of preventive interventions. The overriding challenge is simultaneous enhancement of sensitivity, resolution, and throughput.
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
- 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
Website Link
www.bioinformatics.med.umich.edu/hupo/ppp
www.ebi.ac.uk/pride
