Advances and Utility of the Human Plasma Proteome

The study of proteins circulating
in blood offers tremendous opportunities
to diagnose, stratify, or possibly prevent diseases. With recent technological
advances and the urgent need to understand the effects of COVID-19,
the proteomic analysis of blood-derived serum and plasma has become
even more important for studying human biology and pathophysiology.
Here we provide views and perspectives about technological developments
and possible clinical applications that use mass-spectrometry­(MS)-
or affinity-based methods. We discuss examples where plasma proteomics
contributed valuable insights into SARS-CoV-2 infections, aging, and
hemostasis and the opportunities offered by combining proteomics with
genetic data. As a contribution to the Human Proteome Organization
(HUPO) Human Plasma Proteome Project (HPPP), we present the Human
Plasma PeptideAtlas build 2021-07 that comprises 4395 canonical and
1482 additional nonredundant human proteins detected in 240 MS-based
experiments. In addition, we report the new Human Extracellular Vesicle
PeptideAtlas 2021-06, which comprises five studies and 2757 canonical
proteins detected in extracellular vesicles circulating in blood,
of which 74% (2047) are in common with the plasma PeptideAtlas. Our
overview summarizes the recent advances, impactful applications, and
ongoing challenges for translating plasma proteomics into utility
for precision medicine.