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

Published March 11, 2022

The Human Proteoform Project separates cell types found in blood.

Rafael D. Melani

A new Blood Proteoform Atlas maps 30,000 unique proteoforms as they appear in 21 different cell types found in human blood. The MagLab's 21 tesla FT-ICR mass spectrometer contributed nearly a third of the atlas' proteoforms.

What did scientists discover?

Melani et al. compiled a Blood Proteoform Atlas (BPA), a clarified map of ~30,000 distinct molecular forms of proteins, or "proteoforms", as they appear in 21 different blood cell types. With the BPA as a reference, this team of MagLab users, headed by Melani, examined proteoforms in patient blood samples and developed a panel of 24 biomarkers for liver transplant rejection.

Why is this important?

Through employment of state-of-the-art instrumentation, including the MagLab's 21T FT-ICR mass spectrometer, proteoforms were identified intact in a form of "top-down" analysis rather than cutting them into small pieces (as is standard practice). This advancement realizes a truly molecular-level understanding of cell type and marks the beginning of a new era for more precise study of proteins in specific cells— the Human Proteoform Project. Using the Atlas as a reference, researchers examined proteoforms in patient blood samples and developed a panel of biomarkers for liver transplant rejection.

Who did the research?

Rafael D. Melani¹, Vincent R. Gerbasi¹, Lissa C. Anderson², et al.

¹Northwestern University; ²National High Magnetic Field Laboratory

Why did they need the MagLab?

High-throughput identification of proteoforms from complex biological samples requires instrumentation capable of high mass resolving power, mass accuracy, sensitivity, and efficiency. The 21 tesla FT-ICR mass spectrometer is state-of-the-art in all these facets and contributed nearly a third of the BPA's proteoforms while accounting for only ~15% of the total instrument time devoted to the project.

Details for scientists

View or download the expert-level Science Highlight, The Blood Proteoform Atlas: A reference map of proteoforms in human blood cells
Read the full-length publication The Blood Proteoform Atlas: A reference map of proteoforms in human hematopoietic cells, in Science

Funding

This research was funded by the following grants: G.S. Boebinger (NSF DMR-1644779); Neil L. Kelleher (Paul G. Allen Frontiers Program award 11715; HuBMAP grant UH3 CA246635-02; NIH P41 GM108569); and others

For more information, contact Christopher Hendrickson.