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dc.contributor.author Toby, Timothy K.
dc.contributor.author Kim, Kyunggon
dc.contributor.author Thomas, Paul M.
dc.contributor.author Fellers, Ryan T.
dc.contributor.author LeDuc, Richard D.
dc.contributor.author Kelleher, Neil L.
dc.contributor.author Demetris, Anthony J.
dc.contributor.author Abecassis, Michael M.
dc.contributor.author Levitsky, Josh M.
dc.date.accessioned 2017-02-08T18:41:07Z
dc.date.available 2017-02-08T18:41:07Z
dc.date.issued 2017
dc.identifier.citation Forthcoming en
dc.identifier.uri http://hdl.handle.net/2022/21229
dc.description.abstract Biomarker profiles diagnostic of acute rejection (AR) in liver transplant (LT) recipients could enhance the diagnosis and management of recipients. Our aim was to identify diagnostic proteoform-resolved signatures for AR in PBMC, using a novel top down proteomics methodology. We processed viable and non-viable PBMC lysates from 24 non-HCV+ LT recipients (age 60±15.6 years, 66.6% male, mean 3.7±3.3 year from LT) undergoing liver biopsy by molecular weight based fractionation and analyzed them by top-down proteomics in 3 steps: 1) Nanocapillary liquid chromatography coupled with high-resolution tandem mass spectrometry, 2) database searching to identify and characterize proteoforms, 3) data processing through a linear hierarchical model matching the study design to quantify proteoform fold changes in AR vs. Tx (normal liver function) vs. ADNR (acute dysfunction without rejection). Differentially abundant proteoforms were seen in patients with AR vs. TX and AR vs. ADNR, suggesting a distinct proteoform signature of AR in LT recipients. This was most evident in the viable cell preparations. Mapping analysis of these proteins back to genes through PANTHER and GO revealed multiple signaling pathways, including inflammation mediated by cytokines and chemokines. Larger studies are needed to validate these signatures and test their predictive value for use in clinical management. en
dc.description.sponsorship Research reported in this publication was supported by the National Institute Of General Medical Sciences of the National Institutes of Health under Award Number P41GM108569. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. en
dc.language.iso en en
dc.publisher American Journal of Transplantation en
dc.relation.ispartofseries Forthcoming;
dc.relation.isversionof Forthcoming en
dc.relation.uri http://purl.dlib.indiana.edu/iusw/data/2022/21229/Toby_Liver_Transplant.zip
dc.rights THE WORK (AS DEFINED BELOW) IS PROVIDED UNDER THE TERMS OF THIS CREATIVE COMMONS PUBLIC LICENSE ("CCPL" OR "LICENSE"). THE WORK IS PROTECTED BY COPYRIGHT AND/OR OTHER APPLICABLE LAW. ANY USE OF THE WORK OTHER THAN AS AUTHORIZED UNDER THIS LICENSE OR COPYRIGHT LAW IS PROHIBITED. BY EXERCISING ANY RIGHTS TO THE WORK PROVIDED HERE, YOU ACCEPT AND AGREE TO BE BOUND BY THE TERMS OF THIS LICENSE. TO THE EXTENT THIS LICENSE MAY BE CONSIDERED TO BE A CONTRACT, THE LICENSOR GRANTS YOU THE RIGHTS CONTAINED HERE IN CONSIDERATION OF YOUR ACCEPTANCE OF SUCH TERMS AND CONDITIONS. en
dc.rights.uri http://creativecommons.org/licenses/by/4.0/ en
dc.subject Top-down proteomics, Translational proteomics, Mass spectrometry, Proteoform, Transplantation, Liver Transplantation, Transplant Rejection, Biomarkers en
dc.title Proteoforms in Peripheral Blood Mononuclear Cells as Novel Rejection Biomarkers in Liver Transplant Recipients en
dc.type Dataset en
dc.identifier.doi Forthcoming


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