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Advances and Utility of the Human Plasma Proteome

Journal

JOURNAL OF PROTEOME RESEARCH
Volume 20, Issue 12, Pages 5241-5263

Publisher

AMER CHEMICAL SOC
DOI: 10.1021/acs.jproteome.1c00657

Keywords

proteomics; mass spectrometry; blood; plasma; Human Proteome Project; Human Plasma Proteome Project; PeptideAtlas; proximity extension assays (PEA by Olink); DNA aptamers (Somascan)

Funding

  1. National Institutes of Health, National Institute of General Medical Sciences [R01GM087221, R24GM127667]
  2. Office of the Director [S10OD026936]
  3. National Institute on Aging [U19AG023122]
  4. National Institute of Environmental Health Sciences [P30ES017885]
  5. National Cancer Institute [U24CA210967]
  6. National Science Foundation [DBI-1933311]
  7. French Investissement Avenir Infra-structures Nationales en Biologie et Sante [ANR-10-INBS-08]
  8. Knut and Alice Wallenberg Foundation
  9. Erling-Persson Family Foundation
  10. Stockholm County Council [HMT 20190962]

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The study of proteins circulating in blood presents significant opportunities for diagnosing, stratifying, or preventing diseases. Recent technological advancements have made the proteomic analysis of blood-derived serum and plasma increasingly important in understanding human biology and pathophysiology. By utilizing mass-spectrometry (MS) or affinity-based methods, valuable insights into SARS-CoV-2 infections, aging, and hemostasis have been gained, along with the potential to combine proteomics with genetic data for further insights. The ongoing challenges include translating plasma proteomics into precision medicine, with recent advances in the field providing impactful applications.
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 COVID19, 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.

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