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.