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

Rafael D. Melani, Vincent R. Gerbasi, Lissa C. Anderson, Jacek W. Sikora, Timothy K. Toby, Josiah E. Hutton, David S. Butcher, Fernanda Negrão, Henrique S. Seckler, Kristina Srzentic, Luca Fornelli, Jeannie M. Camarillo, Richard D. LeDuc, Anthony J. Cesnik, Emma Lundberg, Joseph B. Greer, Ryan T. Fellers, Matthew T. Robey, Caroline J. DeHart, Eleonora ForteChristopher L. Hendrickson, Susan E. Abbatiello, Paul M. Thomas, Andy I. Kokaji, Josh Levitsky, Neil L. Kelleher*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)411-418
Number of pages8
JournalScience
Volume375
Issue number6579
DOIs
StatePublished - Jan 28 2022

ASJC Scopus subject areas

  • General

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