Validation of systems biology derived molecular markers of renal donor organ status associated with long term allograft function

Abstract Donor organ quality affects long term outcome after renal transplantation. A variety of prognostic molecular markers is available, yet their validity often remains undetermined. A network-based molecular model reflecting donor kidney status based on transcriptomics data and molecular featur...

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Autores principales:	Paul Perco, Andreas Heinzel, Johannes Leierer, Stefan Schneeberger, Claudia Bösmüller, Rupert Oberhuber, Silvia Wagner, Franziska Engler, Gert Mayer
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/507e83aa5dbe41db9756727a34d40122
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spelling	oai:doaj.org-article:507e83aa5dbe41db9756727a34d401222021-12-02T11:41:12ZValidation of systems biology derived molecular markers of renal donor organ status associated with long term allograft function10.1038/s41598-018-25163-82045-2322https://doaj.org/article/507e83aa5dbe41db9756727a34d401222018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25163-8https://doaj.org/toc/2045-2322Abstract Donor organ quality affects long term outcome after renal transplantation. A variety of prognostic molecular markers is available, yet their validity often remains undetermined. A network-based molecular model reflecting donor kidney status based on transcriptomics data and molecular features reported in scientific literature to be associated with chronic allograft nephropathy was created. Significantly enriched biological processes were identified and representative markers were selected. An independent kidney pre-implantation transcriptomics dataset of 76 organs was used to predict estimated glomerular filtration rate (eGFR) values twelve months after transplantation using available clinical data and marker expression values. The best-performing regression model solely based on the clinical parameters donor age, donor gender, and recipient gender explained 17% of variance in post-transplant eGFR values. The five molecular markers EGF, CD2BP2, RALBP1, SF3B1, and DDX19B representing key molecular processes of the constructed renal donor organ status molecular model in addition to the clinical parameters significantly improved model performance (p-value = 0.0007) explaining around 33% of the variability of eGFR values twelve months after transplantation. Collectively, molecular markers reflecting donor organ status significantly add to prediction of post-transplant renal function when added to the clinical parameters donor age and gender.Paul PercoAndreas HeinzelJohannes LeiererStefan SchneebergerClaudia BösmüllerRupert OberhuberSilvia WagnerFranziska EnglerGert MayerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-9 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Paul Perco Andreas Heinzel Johannes Leierer Stefan Schneeberger Claudia Bösmüller Rupert Oberhuber Silvia Wagner Franziska Engler Gert Mayer Validation of systems biology derived molecular markers of renal donor organ status associated with long term allograft function
description	Abstract Donor organ quality affects long term outcome after renal transplantation. A variety of prognostic molecular markers is available, yet their validity often remains undetermined. A network-based molecular model reflecting donor kidney status based on transcriptomics data and molecular features reported in scientific literature to be associated with chronic allograft nephropathy was created. Significantly enriched biological processes were identified and representative markers were selected. An independent kidney pre-implantation transcriptomics dataset of 76 organs was used to predict estimated glomerular filtration rate (eGFR) values twelve months after transplantation using available clinical data and marker expression values. The best-performing regression model solely based on the clinical parameters donor age, donor gender, and recipient gender explained 17% of variance in post-transplant eGFR values. The five molecular markers EGF, CD2BP2, RALBP1, SF3B1, and DDX19B representing key molecular processes of the constructed renal donor organ status molecular model in addition to the clinical parameters significantly improved model performance (p-value = 0.0007) explaining around 33% of the variability of eGFR values twelve months after transplantation. Collectively, molecular markers reflecting donor organ status significantly add to prediction of post-transplant renal function when added to the clinical parameters donor age and gender.
format	article
author	Paul Perco Andreas Heinzel Johannes Leierer Stefan Schneeberger Claudia Bösmüller Rupert Oberhuber Silvia Wagner Franziska Engler Gert Mayer
author_facet	Paul Perco Andreas Heinzel Johannes Leierer Stefan Schneeberger Claudia Bösmüller Rupert Oberhuber Silvia Wagner Franziska Engler Gert Mayer
author_sort	Paul Perco
title	Validation of systems biology derived molecular markers of renal donor organ status associated with long term allograft function
title_short	Validation of systems biology derived molecular markers of renal donor organ status associated with long term allograft function
title_full	Validation of systems biology derived molecular markers of renal donor organ status associated with long term allograft function
title_fullStr	Validation of systems biology derived molecular markers of renal donor organ status associated with long term allograft function
title_full_unstemmed	Validation of systems biology derived molecular markers of renal donor organ status associated with long term allograft function
title_sort	validation of systems biology derived molecular markers of renal donor organ status associated with long term allograft function
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/507e83aa5dbe41db9756727a34d40122
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Validation of systems biology derived molecular markers of renal donor organ status associated with long term allograft function

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