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

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 similar to 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.

Automated summary

By studying the proteoforms expressed from human genes in different cell types and bodily fluids, we found that proteoforms provide a better description of protein-level biology and serve as more specific indicators of cell differentiation compared to proteins. In the context of liver transplantation, we utilized the Blood Proteoform Atlas to identify cell and proteoform signatures that distinguish normal graft function from graft dysfunction.