Spatial top-down proteomics for the functional characterization of human kidney
We developed an integrated workflow to directly identify proteoforms and reveal their spatial distributions. Of the 20 differentially abundant proteoforms identified as discriminate between tubules and glomeruli by microPOTS, the vast majority of tubular proteoforms were of mitochondrial origin (8 of 10) while discriminate proteoforms in glomeruli were primarily hemoglobin subunits (9 of 10). These trends were also identified within ion images demonstrating spatially resolved characterization of proteoforms that has the potential to reshape discovery-based proteomics because the proteoforms are the ultimate effector of cellular functions. Applications of this technology have the potential to unravel etiology and pathophysiology of disease states, informing on biologically active proteoforms, which remodel the proteomic landscape in chronic and acute disorders.
Authors
- Ying Zhu (ORCID: https://orcid.org/0000-0002-5416-0566)
- James M. Fulcher (ORCID: https://orcid.org/0000-0001-9033-3623)
- Dušan Veličković (ORCID: https://orcid.org/0000-0001-7945-9620)
- Ronald Moore (ORCID: https://orcid.org/0000-0003-2806-2855)
- Mowei Zhou (ORCID: https://orcid.org/0000-0003-3575-3224)
- Yen‐Chen Liao (ORCID: https://orcid.org/0000-0002-8124-0457)
- Marija Veličković (ORCID: https://orcid.org/0000-0003-3664-5719)
- David J. Degnan (ORCID: https://orcid.org/0000-0001-5737-7173)
- Ljiljana Paša‐Tolić
- L.A. Lewis (ORCID: https://orcid.org/0000-0003-2301-300X)
- Lisa Bramer (ORCID: https://orcid.org/0000-0002-8384-1926)
- Rashmi Kumar (ORCID: https://orcid.org/0000-0001-8994-5091)
- Kevin Zemaitis (ORCID: https://orcid.org/0000-0002-3524-9776)
- Sarah Williams (ORCID: https://orcid.org/0000-0002-0175-466X)
Institutions
- Pacific Northwest National Laboratory (US)
- Environmental Molecular Sciences Laboratory (US)
- Genomic Health (United States) (US)
- Zhejiang University (CN)
Publication Details
- Journal
- Clinical Proteomics
- Published
- 2025-03-05
- DOI
- https://doi.org/10.1186/s12014-025-09531-x
- Citations
- 6
- Primary Topic
- Advanced Proteomics Techniques and Applications
- Type
- article
- Field-Weighted Citation Impact
- 3.78
Funders
- U.S. Department of Energy
- Vanderbilt University
- Northwestern University
- National Institutes of Health
- Office of Science
- Biological and Environmental Research
- Pacific Northwest National Laboratory
- Common Fund