Validation of systems biology derived molecular markers of donor organ status associated with long term allograft function
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE95026 | GEO | 2018/05/04
REPOSITORIES: GEO
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Project description: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.
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Project description:The Australian Chronic Allograft Dysfunction (AUSCAD) study is an ongoing single centre cohort study at Westmead hospital in Australia. In this section of the study, we aimed to identify biomarkers for allograft rejection in kidney transplant recipients, 3-months after their transplant. Our study recruited 123 patients, each having protocol renal allograft biopsies taken 3-months post transplantation.
2024-04-05 | GSE261892 | GEO
Project description:Genomic Analysis of more than 400 patients from multi-center transplant programs and clinical trials provides a non-invasive QPCR based gene expression test for operational renal allograft tolerance 3 group comparison of blood from TOL, CAN and Non-transplant healthy controls (HD) allografts. Biological replicates: 16 TOL, 10 CAN and 5 HC
2015-01-08 | E-GEOD-45218 | biostudies-arrayexpress
Project description:Genomic Analysis of more than 400 patients from multi-center transplant programs and clinical trials provides a non-invasive QPCR based gene expression test for operational renal allograft tolerance
2015-01-08 | GSE45218 | GEO
Project description:The Australian Chronic Allograft Dysfunction (AUSCAD) study is an ongoing single centre cohort study at Westmead hospital in Australia. In this section of the study, we aimed to identify biomarkers for chronic allograft dysfunction in kidney transplant recipients. Our study recruited 136 patients, each having protocol renal allograft biopsies taken pre transplantation.
2024-04-05 | GSE261240 | GEO
Project description:In contrast to opt-in systems, relatively little is known about what influences whether or not people register a decision about organ donation in opt-out systems. We address this gap in the literature. Participants (N = 756) living in a country with opt-out consent (Wales, UK) provided information on demographics and blood donor status. Participants indicated whether they had opted-in or opted-out (i.e. active decision), or not registered a decision under the assumption of deemed consent. Subsequently, their negative emotional beliefs (or affective attitudes) towards organ donation were measured. Opting-in was associated with being younger, having donated blood and holding superstitious beliefs about donation (jinx). Disgust (ick factor) deterred opting-in, and bodily integrity concerns increased opting-out. Positive affective attitudes increased opting-in and deterred opting-out. Actively opting-in increases the likelihood of organs being transplanted, thus, modifying affective attitudes and targeting blood donors should enhance the number of donors available under opt-out systems.
| S-EPMC11264565 | biostudies-literature
Project description:A systems biology approach was used to comprehensively examine the impact of renal disease and hemodialysis (HD) on host response during critical illness. We examined the metabolome, proteome, and transcriptome of 150 patients with critical illness, stratified by renal function. Plasma metabolite values showed greater changes as renal function declined, with the greatest derangements in patients receiving chronic HD. Specifically, 6 uremic retention molecules, 17 other protein catabolites, 7 modified nucleosides, and 7 pentose phosphate sugars increased as renal function declined, consistent with decreased excretion or increased catabolism of amino acids and ribonucleotides. Similarly, the proteome showed increased levels of low-molecular weight proteins and acute phase reactants. The transcriptome revealed a broad-based decrease in mRNA levels among HD patients. Systems integration revealed an unrecognized association between plasma RNASE1 and several RNA catabolites and modified nucleosides. Further, allantoin, N1-methyl-4-pyridone-3-carboxamide, and n-acetylaspartate showed inverse correlations with the majority of significantly down-regulated genes. In conclusion, renal function broadly affected the plasma metabolome, proteome, and peripheral blood transcriptome during critical illness. These changes were not effectively mitigated by hemodialysis. These studies suggest several novel mechanisms whereby renal dysfunction contributes to critical illness.
2015-07-01 | GSE67401 | GEO
Project description:A systems biology approach was used to comprehensively examine the impact of renal disease and hemodialysis (HD) on host response during critical illness. We examined the metabolome, proteome, and transcriptome of 150 patients with critical illness, stratified by renal function. Plasma metabolite values showed greater changes as renal function declined, with the greatest derangements in patients receiving chronic HD. Specifically, 6 uremic retention molecules, 17 other protein catabolites, 7 modified nucleosides, and 7 pentose phosphate sugars increased as renal function declined, consistent with decreased excretion or increased catabolism of amino acids and ribonucleotides. Similarly, the proteome showed increased levels of low-molecular weight proteins and acute phase reactants. The transcriptome revealed a broad-based decrease in mRNA levels among HD patients. Systems integration revealed an unrecognized association between plasma RNASE1 and several RNA catabolites and modified nucleosides. Further, allantoin, N1-methyl-4-pyridone-3-carboxamide, and n-acetylaspartate showed inverse correlations with the majority of significantly down-regulated genes. In conclusion, renal function broadly affected the plasma metabolome, proteome, and peripheral blood transcriptome during critical illness. These changes were not effectively mitigated by hemodialysis. These studies suggest several novel mechanisms whereby renal dysfunction contributes to critical illness. We sequenced peripheral blood RNA of 133 representative subjects with systemic inflammatory response syndrome that had Acute Kidney Injury (AKI) or Hemodialysis (HD). No injury (AKI0; n= 58); AKI Stage 1 (AKI1; n= 36); AKI stage 2 and 3 (AKI23; n= 17); HD (N=22).
2015-07-01 | E-GEOD-67401 | biostudies-arrayexpress
Project description:Kidney transplantation offers the best survival and quality of life for patients’ with end-stage kidney disease. The major barrier to successful long-term transplantation is the host’s immune response to alloantigens’ causing rejection of the transplant. The complexity of this immune response in kidney transplantation is still not fully understood and effective treatment strategies are needed. To better understand rejection at the molecular and cellular level we characterized 4,487 cells from a single biopsy core from a kidney transplant undergoing mixed rejection using single cell RNA sequencing.
2018-06-19 | GSE109564 | GEO
Project description:In this study, we evaluated transcriptional responses in circulating leukocytes to assess for biomarkers of adverse outcomes in transplant patients after transplantation from a HCV-infected donor. We enrolled renal transplant recipients with and without HCV and performed RNA sequencing on serial samples. CMV DNAemia and allograft rejection outcomes were measured. Regularized logistic regression was utilized to develop gene expression classifiers predictive of clinical outcomes.
2023-02-08 | GSE213705 | GEO