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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.
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


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.

Tools They use

This research was conducted in the 21 T FT-ICR mass spectrometer at the MagLab's ICR Facility.

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Last modified on 26 December 2022