Plasma Proteome Database as a resource for proteomics research: 2014 update

Abstract

Plasma Proteome Database (PPD; http://www.plasmaproteomedatabase.org/) was initially described in the year 2005 as a part of Human Proteome Organization's (HUPO's) pilot initiative on Human Plasma Proteome Project. Since then, improvements in proteomic technologies and increased throughput have led to identification of a large number of novel plasma proteins. To keep up with this increase in data, we have significantly enriched the proteomic information in PPD. This database currently contains information on 10,546 proteins detected in serum/plasma of which 3784 have been reported in two or more studies. The latest version of the database also incorporates mass spectrometry-derived data including experimentally verified proteotypic peptides used for multiple reaction monitoring assays. Other novel features include published plasma/serum concentrations for 1278 proteins along with a separate category of plasma-derived extracellular vesicle proteins. As plasma proteins have become a major thrust in the field of biomarkers, we have enabled a batch-based query designated Plasma Proteome Explorer, which will permit the users in screening a list of proteins or peptides against known plasma proteins to assess novelty of their data set. We believe that PPD will facilitate both clinical and basic research by serving as a comprehensive reference of plasma proteins in humans and accelerate biomarker discovery and translation efforts.

Figure 1.

Data analysis workflow using Plasma Proteome Explorer and a screenshot of a ‘Molecule Page’ for Haptoglobin in PPD. When queried using UniProt IDs (as shown in A), the plasma proteome explorer displays two different type of results (shown in B). These correspond to (i) proteins present in PPD, which are hyperlinked to their corresponding molecule pages and (ii) proteins not present in PPD, which are linked to an external database, UniProt. Clicking the molecule leads the user to the respective molecule page (shown in C). The graphical representation shows domains and motifs found in the protein. The molecule page also displays the alternate localization of protein, the associated biological process and molecular function of the protein. In addition, the plasma concentration reported in healthy individuals along with corresponding PubMed identifiers and any other information regarding presence in plasma EVs is displayed. Further, MRM data is provided with information on proteotypic peptides, peptide m/z values, charge, collision energy, transitions determined, type of fragment ions and the mass spectrometer used along with a link to the corresponding publication (shown in D).

Figure 2.

Distribution of proteins annotated in PPD according to number of corresponding publications. The histogram shows that a high number of proteins (8793 proteins) in plasma have been reported only in a single study. Of the 509 articles annotated, 426 were found to support the presence of ≤10 proteins in plasma or serum.