The Human Plasma Proteome Draft of 2017: Building on the Human Plasma PeptideAtlas from Mass Spectrometry and Complementary Assays

Abstract

Human blood plasma provides a highly accessible window to the proteome of any individual in health and disease. Since its inception in 2002, the Human Proteome Organization’s Human Plasma Proteome Project (HPPP) has been promoting advances in the study and understanding of the full protein complement of human plasma and on determining the abundance and modifications of its components. In 2017, we review the history of the HPPP and the advances of human plasma proteomics in general, including several recent achievements. We then present the latest 2017-04 build of Human Plasma PeptideAtlas, which yields ~43 million peptide-spectrum matches and 122,730 distinct peptide sequences from 178 individual experiments at a 1% protein-level FDR globally across all experiments. Applying the latest Human Proteome Project Data Interpretation Guidelines, we catalog 3509 proteins that have at least two non-nested uniquely-mapping peptides of 9 amino acids or more and >1300 additional proteins with ambiguous evidence. We apply the same two-peptide guideline to historical PeptideAtlas builds going back to 2006 and examine the progress made in the past ten years in plasma proteome coverage. We also compare the distribution of proteins in historical PeptideAtlas builds in various RNA-abundance and cellular localization categories. We then discuss advances in plasma proteomics based on targeted mass spectrometry as well as affinity assays, which during early 2017 target ~2000 proteins. Finally we describe considerations about sample handling and study design, concluding with an outlook for future advances in deciphering the human plasma proteome.

Body composition in anorexia nervosa: Meta‐analysis and meta‐regression of cross‐sectional and longitudinal studies

“…Most importantly, blood comprises approximately 3,500 highly correlated and interacting proteins (http://hupo.org; Schwenk et al, ) and 4,600 metabolites (serummetabolome.ca; Psychogios et al, ); therefore, the measurement of single proteins, hormones, or metabolites is ill‐advised. Metabolomics, proteomics, and lipidomics can capture large amounts of information at adequate statistical power when used in large samples (Hernandes et al, ).…”

Mass Spectrometry-Based Plasma Proteomics: Considerations from Sample Collection to Achieving Translational Data

“…Towards answering this question, and improving the overall performance and coverage of plasma proteomics experiments, we recommend that researchers consider key components of a proposed plasma proteomics workflow outlined in Figure 2 below. Using data collected for the 2017 draft of the human plasma and serum proteome (hosted by PeptideAtlas 16 ), proteins (in red) are plotted as a function of their concentration rank (x-axis) and the number of studies in which they were identified (y-axis, left). The identified proteins (solid black line) are also plotted as a function of their concentration rank (x-axis) and their estimated concentration (y-axis, right).…”

Quantification of protein markers monitoring the pre‐analytical effect of blood storage time before plasma isolation using 15N metabolically labeled recombinant proteins

“…The informed consent was obtained from the study participants, and the institutional review board of the Seoul National University Bundang Hospital approved the main study. Prior to plasma preparation process, we stored the fraction of blood samples of two study participants for varying timeperiods (3,6,12,24, and 48 hours) and at two different temperatures (4°C and 25°C). The tubes were spun at 1500 × g, at 25°C for 10 minutes in a swing-bucket centrifuge.…”

“…In the hospital, blood‐based molecular diagnosis is a routine process. In HUPO2006, researchers recommended using human plasma with EDTA for proteomic experiments and discussed sample processing procedures a lot thereafter . However, there has been no further compliance or guideline about the pre‐analytical effects that occur when plasma is separated from whole blood.…”

“…In HUPO2006, researchers recommended using human plasma with EDTA for proteomic experiments 1 and discussed sample processing procedures a lot thereafter. 2,3 However, there has been no further compliance or guideline about the pre-analytical effects that occur when plasma is separated from whole blood. The abundances of some proteins may change during the process of blood collection and storage before plasma isolation.…”