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

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 nine 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.

Possibilities of extraction and characterization of ancient plasma proteins in archaeological bones.

Due to the mineral matrix bone proteins are capable of surviving during centuries after inhumation, but cross-linking with other bone proteins as well as fragmentation and complex reactions with humic acids and microorganisms lead to considerable alterations in molecular weight and structure of these proteins. Our group concentrates on polymorphic plasma proteins which diffuse out of the capillary system into the bone matrix where they adsorb to the mineralic substrate. So far, only little is known about the degradation and alteration of these proteins in fossil bones. It has to be evaluated whether the aged proteins still contain some of the information which renders them a valuable tool for forensic questions and population genetics in recent populations. Therefore we tried by modification of already existing methods to expand plasma protein identification and subtyping into the new field of aged plasma proteins.

[Serum proteins in human skeletal remains]. / Serumproteine in menschlichem Skelettmaterial.

The analysis of non-mineralbound, non-collagenous proteins from ancient Peruvian human bones with electrophoretical methods, SDS-polyacrylamide-electrophoresis and isoelectric focusing, results in molecular weight bands on the one hand and a pH-gradient distribution on the other hand, which are perhaps connected with polymorphic serum proteins. A specific protein identification is possible with immunological methods.

Molecular preservation and isotopy of Mesolithic human finds from the Ofnet cave (Bavaria, Germany).

Favourable burial conditions and self-limiting decomposition processes led to an extraordinarily well molecular preservation of the Mesolithic human skull finds from the Ofnet cave (district Nördlingen, Bavaria). Beyond the extraction of bone collagen, a selection of serum proteins from bone was identified immunologically. Stable carbon and nitrogen isotope ratios from collagen gave clues to dietary behaviour including nursing practices. Diverging results after the application of biochemical protocols (for protein cleaning) and biophysical methods (for stable isotope analysis) are of particular interest: while the first approach failed to quantitatively eliminate anorganic contaminations, the second left some organic, exogenous residues in the samples. Thus, methods for protein extraction must vary according to problem solution and ultimate aim of the study. Taking this into account, application of invasive methods is also encouraged to rare and valuable skeletal finds.

Vroman effects, techniques, and philosophies.

Leo Vroman's work on blood-materials interaction over the years has motivated and influenced much of our work in this field. Here we show how most of our studies on proteins at interfaces can be traced to Vroman's ideas presented in Blood over 25 years ago. Specifically, we briefly discuss simple proteins at simple interfaces, complex interfaces, complex proteins at interfaces, multi-parameter phenomena, and scientific communication and education.