The Blood Proteoform Atlas: A reference map of proteoforms in human hematopoietic cells

Science. 2022 Jan 28;375(6579):411-418. doi: 10.1126/science.aaz5284. Epub 2022 Jan 27.

Abstract

Human biology is tightly linked to proteins, yet most measurements do not precisely determine alternatively spliced sequences or posttranslational modifications. Here, we present the primary structures of ~30,000 unique proteoforms, nearly 10 times more than in previous studies, expressed from 1690 human genes across 21 cell types and plasma from human blood and bone marrow. The results, compiled in the Blood Proteoform Atlas (BPA), indicate that proteoforms better describe protein-level biology and are more specific indicators of differentiation than their corresponding proteins, which are more broadly expressed across cell types. We demonstrate the potential for clinical application, by interrogating the BPA in the context of liver transplantation and identifying cell and proteoform signatures that distinguish normal graft function from acute rejection and other causes of graft dysfunction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alternative Splicing
  • B-Lymphocytes / chemistry
  • Blood Cells / chemistry*
  • Blood Proteins / chemistry*
  • Blood Proteins / genetics
  • Bone Marrow Cells / chemistry*
  • Cell Lineage
  • Databases, Protein*
  • Humans
  • Leukocytes, Mononuclear / chemistry
  • Liver Transplantation
  • Plasma / chemistry
  • Protein Isoforms / chemistry*
  • Protein Isoforms / genetics
  • Protein Processing, Post-Translational
  • Proteome / chemistry*
  • Proteomics
  • T-Lymphocytes / chemistry

Substances

  • Blood Proteins
  • Protein Isoforms
  • Proteome