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Comparative top down proteomics of peripheral blood mononuclear cells from kidney transplant recipients with normal kidney biopsies or acute rejection
Author(s) -
Savaryn John P.,
Toby Timothy K.,
Catherman Adam D.,
Fellers Ryan T.,
LeDuc Richard D.,
Thomas Paul M.,
Friedewald John J.,
Salomon Daniel R.,
Abecassis Michael M.,
Kelleher Neil L.
Publication year - 2016
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.201600008
Subject(s) - proteomics , kidney , peripheral blood mononuclear cell , biomarker , metabolomics , quantitative proteomics , biology , transcriptome , immune system , biopsy , computational biology , immunology , pathology , bioinformatics , medicine , gene , gene expression , biochemistry , endocrinology , in vitro
Recent studies utilizing transcriptomics, metabolomics, and bottom up proteomics have identified molecular signatures of kidney allograft pathology. Although these results make significant progress toward non‐invasive differential diagnostics of dysfunction of a transplanted kidney, they provide little information on the intact, often modified, protein molecules present during progression of this pathology. Because intact proteins underpin diverse biological processes, measuring the relative abundance of their modified forms promises to advance mechanistic understanding, and might provide a new class of biomarker candidates. Here, we used top down proteomics to inventory the modified forms of whole proteins in peripheral blood mononuclear cells (PBMCs) taken at the time of kidney biopsy for 40 kidney allograft recipients either with healthy transplants or those suffering acute rejection. Supported by gas‐phase fragmentation of whole protein ions during tandem mass spectrometry, we identified 344 proteins mapping to 2905 distinct molecular forms (proteoforms). Using an initial implementation of a label‐free approach to quantitative top down proteomics, we obtained evidence suggesting relative abundance changes in 111 proteoforms between the two patient groups. Collectively, our work is the first to catalog intact protein molecules in PBMCs and suggests differentially abundant proteoforms for further analysis.