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HUPO Plasma Proteome Project 2007 Workshop Report

2007; Elsevier BV; Volume: 6; Issue: 12 Linguagem: Inglês

10.1074/mcp.h700012-mcp200

1535-9484

Gilbert S. Omenn, Ruedi Aebersold, Young‐Ki Paik,

Mass Spectrometry Techniques and Applications

The HUPO Plasma Proteome Project (PPP) 1The abbreviations used are: PPP, HUPO Plasma Proteome Project; PRIDE, Proteomics Identification Database. held its annual workshop at the 6th HUPO World Congress in Seoul, Korea, October 7, 2007. The agenda was organized around the aims of the next phase of the PPP. The pilot phase accomplished its goals of providing reference specimens of serum and plasma to a large international network of collaborating laboratories, comparing protein identifications with various fractionation and analytical technology platforms, introducing new technologies from vendor partners, generating extensive submissions to open source databases (www.peptideatlas.org/hupo/hppp (ISB); www.ebi.ac.uk/pride (EBI)) and bioinformatics insights, and laying a foundation for integration of plasma studies with organ proteome and disease biomarker projects. Results were published in a special issue of Proteomics (1Omenn G.S. States D.J. Adamski M.R. Blackwell T.W. Menon R. Hermjakob H. Apweiler R. Haab B.B. Simpson R.J. Eddes J.S. Kapp E.A. Maritz R.L. Chang D.W. Rai A.J. Admon A. Aebersold R. Eng J. Hancock W.S. Hefta S.A. Meyer H. Paik Y.-K. Yoo J.-S. Ping P. Ponnols J. Adkins J. Qian X. Wang R. Wasinger V. Wu C.Y. Zhao X. Zeng R. Archakov A. Tsugita A. Beer I. Pandey A. Pisano M. Andrews P. Tammen H. Speicher D.W. Hanash S.H. Overview of the HUPO Plasma Proteome Project: Results from the pilot phase with 35 collaborating laboratories and multiple analytical groups, generating a core dataset of 3020 proteins and a publicly-available database.Proteomics. 2005; 5: 3223-3519Crossref PubMed Scopus (39) Google Scholar) 2This citation refers to just one of the articles used in this publication. , a Wiley book (2Omenn G.S. Exploring the Human Plasma Proteome. Wiley-Liss, Weiheim, Germany2006Crossref Scopus (0) Google Scholar), and a special analysis in Nature Biotechnology (3States P.J. Omenn G.S. Blackwell T.W. Fermin D. Eng J. Speicher D.W. Hanash S.M. Challenges in deriving high-confidence protein identifications from data gathered by HUPO plasma proteome collaborative study.Nature Biotechnol. 2006; 24: 333-338Crossref PubMed Scopus (286) Google Scholar). The specimens and databases have been utilized for many other studies. Participants at the PPP workshop in Long Beach, California, in November 2006 agreed to develop the current plans. The 2007 workshop was organized with panels of leading scientists in proteomics describing their commitments. The overriding principle is the sharing of data to advance the field and facilitate much needed comparative analyses. The first panel comprised laboratory leaders with advanced technology platforms. Ruedi Aebersold described the N-glycosite Nx(S/T) proteotypic peptide library approach for targeted analyses. Christie Hunter presented applications of multiple reaction monitoring with multiple transitions for each labeled peptide. Denis Hochstrasser emphasized the pre-analytical variables and the advantages of starting from tissue, followed by the multiplex analyses of plasma (or serum, if immunoassays). Bill Hancock introduced multilectin affinity chromatography for glycoproteins, including glycan characterization. Ole Jensen introduced microparticles and phosphoprotein analyses. Richard Smith explained powerful ion mobility separation mass spectrometry and electrospray emitter design. And Rong Zeng presented label-free, integrated analyses after ethanol precipitation and pH elution of plasma proteins from diabetics. The second panel presented highly complementary bioinformatics and database resources already impressively connected with the PPP. Henry Lam announced that PeptideAtlas at the Institute for Systems Biology now has a human PPP-specific subatlas (see above); as the total resource has grown, more and more of the newly reported multiobserved peptides are confirmatory. PeptideAtlas applies to submitted datasets its uniform data analysis pipeline, including MS/MS spectral library searches with SpectraST (joint with the National Institute of Standards and Technology), which are much faster than Sequest. Lennart Martens described typical pitfalls in the analysis of mass spectrometry data obtained from serum or plasma samples along with tools that help resolve these problems. He reported that the PPP datasets were the first external data submitted to PRIDE at the European Bioinformatics Institute (see above); PRIDE assists data dissemination and links to EBI resources. Ron Beavis noted that the PPP was also one of the first datasets in the Global Proteome Machine, GPMdb (with the distinctive prefix 101). Martin McIntosh emphasized statistical variables, starting with variability among individuals and populations to be studied and discussed that follow-up analysis of the same individual minimizes genetic variation. Akhilesh Pandey described the Proteinpedia portal for sharing protein data and annotations. Both PRIDE and Proteinpedia use Tranche at ProteomeCommons.org, created by Philip Andrews of the University of Michigan, for storage of large volume raw datasets. Tranche provides encrypted file sharing among collaborators as well as open access datasets when made available. Contributors to the PPP should submit complex datasets with full experimental annotation specified by the HUPO Protein Standards. Users can find unaltered submissions at PRIDE, X!Tandem analyses at Global Proteome Machine, and TransProteomic Pipeline-processed datasets at PeptideAtlas. The final panel, moderated by John Bergeron as chair of HUPO Initiatives, demonstrated that the PPP and all other HUPO initiatives are complementary. EDTA-plasma specimens should be collected as part of organ-based studies for analysis in the same laboratories, followed by sharing of data on plasma and tissue findings with the PPP through the informatics resources just described. Helmut E. Meyer (Brain Proteome Project) reinforced the priority for starting from (brain) tissue rather than blood and then seeking evidence from direct measurement or consultation of the PPP databases for presence of candidate markers in plasma. Naoyuki Taniguchi (Glycomics Initiative) emphasized the information content and demonstrated disease biomarker value from glycans, especially fucosylated proteins. Jan Schnitzer (Vascular Proteome) noted the contribution of the endothelium and microblebs and microparticles to the plasma proteome. Fuchu He (Liver Proteome Project) pointed out that the liver is the primary source of plasma proteins and noted comparisons of large numbers of liver proteins with proteins reported in the PPP. Finally, Tadashi Yamamoto (Kidney/Urine Proteome Project) focused on the contribution of the blood to proteins identified in the kidney glomerulus and tubule fractions and in urine and reported the value of the Human Protein Atlas for immunohistochemical results. The first two datasets submitted for the New Phase of the PPP are from the Aebersold and Smith laboratories (4Zhang H. Liu A.Y. Loriaux P. Wollscheid B. Zhou Y. Watts J.D. Aebersold R. Mass spectrometric detection of tissue proteins in plasma.Mol. Cell. Proteomics. 2007; 6: 64-71Abstract Full Text Full Text PDF PubMed Scopus (161) Google Scholar, 5Liu T. Qian W.-J. Gritsenko M.A. Xiao W. Moldawer L.L. Kaushal A. Monroe M.E. Varnum S.M. Moore R.J. Purvine S.O. Maier R.V. Davis R.W. Tompkins R.G. Camp II, D.G. Smith R.D. Inflammation and the Host Response to Injury Large Scale Collaborative Research ProgramHigh dynamic range characterization of the trauma patient plasma proteome.Mol. Cell. Proteomics. 2006; 5: 1899-1913Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar). HUPO encourages all investigators and each of the initiatives to make plasma a “common pathway” for development, confirmation, and validation of biomarkers and to provide tissue and plasma results in real-time for collaborative analyses. 3Individuals seeking to become involved in the PPP or recommending published or emerging studies whose datasets would be of interest may contact G. S. Omenn at [email protected] Those seeking guidance on submission of datasets may contact L. Martens at [email protected] and E. Deutsch at [email protected]