Acute renal allograft rejection is an important complication in kidney transplantation. Accurate diagnosis of rejection events is necessary for timely response and treatment. We illustrate the usefulness and biological relevance of selected multivariate approaches to detect rejection from genomic and proteomic signals. The data was used to study gene expression changes using whole genome microarray analysis of peripheral blood from subjects with acute rejection (n=20) and non-rejecting controls (n=20) to obtain insight into the molecular and biological causation of acute renal allograft rejection when combined with proteomics (iTRAQ) data for the same patients/time-points.
Novel multivariate methods for integration of genomics and proteomics data: applications in a kidney transplant rejection study.
Sex, Specimen part, Race
View SamplesRenal failure is characterized by important biological changes resulting in profound pleomorphic physiological effects termed uremia, whose molecular causation is not well understood. The data was used to study gene expression changes in uremia using whole genome microarray analysis of peripheral blood from subjects with end-stage renal failure (n=63) and healthy controls (n=20) to obtain insight into the molecular and biological causation of this syndrome.
Alteration of human blood cell transcriptome in uremia.
Sex, Specimen part, Disease, Disease stage, Race
View SamplesAcute cardiac allograft rejection is a serious complication of heart transplantation. Investigating molecular processes in whole blood via microarrays is a promising avenue of research in transplantation, particularly due to the non-invasive nature of blood sampling. However, whole blood is a complex tissue and the consequent heterogeneity in composition amongst samples is ignored in traditional microarray analysis. This complicates the biological interpretation of microarray data. Here we have applied a statistical deconvolution approach, cell-specific significance analysis of microarrays (csSAM), to whole blood samples from subjects either undergoing acute heart allograft rejection (AR) or not (NR). We identified eight differentially expressed probe-sets significantly correlated to monocytes (mapping to 6 genes, all down-regulated in ARs versus NRs) at a false discovery rate (FDR) <= 15%. None of the genes identified are present in a biomarker panel of acute heart rejection previously published by our group and discovered in the same data.
White blood cell differentials enrich whole blood expression data in the context of acute cardiac allograft rejection.
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View SamplesAcute rejection in cardiac transplant patients is still a contributing factor to limited survival of the implanted heart. Currently there are no biomarkers in clinical use that can predict, at the time of transplantation, the likelihood of post-transplantation acute rejection, which would be of great importance for personalizing immunosuppressive treatment. Within the Biomarkers in Transplantation initiative, the predictive biomarker discovery focused on data and samples collected before or during transplantation such as: clinical variables, genes and proteins from the recipient, and genes from the donor. Based on this study, the best predictive biomarker panel contains genes from the recipient whole blood and from donor endomyocardial tissue and has an estimated area under the curve of 0.90. This biomarker panel provides clinically relevant prediction power and may help personalize immunosuppressive treatment and frequency of rejection monitoring.
Predicting acute cardiac rejection from donor heart and pre-transplant recipient blood gene expression.
Sex, Age, Specimen part, Race
View SamplesThe objective of this study was to examine the effect of dietary restriction and subsequent re-alimentation induced compensatory growth on the global gene expression profile of jejunum epithelial Holstein Friesian bulls (n=40) were assigned to one of two groups: restricted feed allowance (RES; n=20) for 125 days (Period 1) followed by ad libitum access to feed for 55 days (Period 2) or (ii) ad libitum access to feed throughout (ADLIB; n=20). All bulls received the same diet of 70% concentrate 30% grass silage through out the experimental trial,with the amount of feed provided different dependent on each treatment group. At the end ofeach period, 10 animals from each treatment group (RES, ADLIB) were slaughtered, and jejunum epithelial collected from all animals. RNA was extracted and jejununal epithelium gene expression was examined using RNAseq technology on all samles collected (end of Period 1: 10 samples each from ADLIB and RES groups; end of Period 2: 10 samples each from ADLIB and RES groups). Dietary restriction and subsequent re-alimentation were associated with altered expression of genes involved in digestion and metabolism, aswell as cellular protection and detoxification in jejunal epithelia. This information may be exploited in genomic breeding programmes to assist selection of cattle with a greater ability to compensate following a period dietary restriction. Overall design: 40 jejunumal epithelium RNA samples were analysed in total. 10 samples were from jejunum epithelium collected at the end of a period of dietary restriction (d 125; Period 1) and 10 samples were from jejunum epithelium collected after 55 days of compensatory growth (d 55 of re-alimentation, Period 2). In addition, RNA was also anlaysed from 10 samples collected from animals fed ad libitum at the end of both Period 1 and Period 2.
Gene co-expression networks contributing to the expression of compensatory growth in metabolically active tissues in cattle.
Specimen part, Subject
View SamplesThe objective of this study was to examine the effect of dietary restriction and subsequent re-alimentation induced compensatory growth on the global gene expression profile of ruminal epithelial papillae. Holstein Friesian bulls (n=38) were assigned to one of two groups: restricted feed allowance (RES; n=19) for 125 days (Period 1) followed by ad libitum access to feed for 55 days (Period 2) or (ii) ad libitum access to feed throughout (ADLIB; n=19). All bulls received the same diet of 70% concentrate 30% grass silage through out the experimental trial,with the amount of feed provided different dependent on each treatment group. At the end of Period 1, 9 animals from each treatment group were slaughtered, with 10 animals from each treatment slaughtered at the end of Period 2. Rumen epithelium was collected from all animals within thirty minutes of slaughter. RNA was extracted and rumen epithelium gene expression was examined using RNAseq technology on all samles collected (end of Period 1: 9 samples each from ADLIB and RES groups; end of Period 2: 10 samples each from ADLIB and RES groups). Genes identified as differentially expressed in response to both dietary restriction and subsequent compensatory growth included those involved in processes such as cellular interactions and transport, protein folding and gene expression, as well as immune response. This information can be exploited in genomic breeding programmes to assist selection of cattle with a greater ability to compensate following a period dietary restriction. Overall design: 38 rumen epithelium RNA samples were analyzed in total. Purebred Holstein Friesian bulls were assigned to one of two feeding treatments (i) restricted feed allowance for 125 days (n=9) followed by ad libitum access to feed for a further 55 days (n=10) or (ii) a control group with ad libitum access to feed through out the 180 days trial (n=19). The first 125 days of the trial were denoted as Period 1, during which treatment groups were fed differentially. The subsequent 55 days, denoted as Period 2 during which all bulls were fed ad libitum. All bulls received the same diet of 70% concentrate 30% grass silage through out the experimental trial, with the amount of feed provided different dependent on each treatment group. Restricted fed animals were fed to grow at 0.6 kg /day during Period 1, with ad libitum animals expected to gain in excess of 1.5 to 2 kg/day.
Gene co-expression networks contributing to the expression of compensatory growth in metabolically active tissues in cattle.
Sex, Specimen part, Subject
View SamplesGenome-wide analysis of decidual transcriptome in pre-eclampsia compared with normotensive controls to find differentially expressed genes/pathways.
Genome-wide transcriptome directed pathway analysis of maternal pre-eclampsia susceptibility genes.
Specimen part, Disease stage
View SamplesPioneering studies within the last few years have allowed the in vitro expansion of tissue-specific adult stem cells from a variety of endoderm-derived organs, including the stomach, small intestine and colon. Here we derived organoids from mouse gallbladder tissue (gallbladder organoids), from mouse liver (including the extrahepatic biliary ducts and gallbladder; liver organoids) and from mouse small intestine tissue (intestinal organoids). RNA was prepared from these organoids and used to assay expression of 21,258 genes using Affymetrix gene expression arrays. RNA was also prepared from mouse gallbladder, liver and small intestine tissues and used to assay gene expression in these tissues. Finally, gallbladder organoids were induced to differentiate by removing R-spondin 1 and noggin from the culture media and subjected to gene expression array analysis.
R-spondin 1 and noggin facilitate expansion of resident stem cells from non-damaged gallbladders.
Specimen part
View SamplesThe aim of this work was to compare the effects of AT, RT, and the full combination (AT/RT) on central ectopic fat, liver enzymes, and fasting insulin resistance [homeostatic model assessment (HOMA)]
A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status.
Age, Specimen part, Subject, Time
View SamplesThe Uppsala Longitudinal Study of Adult Men is a population-based study aimed at identifying risk factors for cardiovascular disease. At the time of biopsy all subjects were ~ 70yr of age
A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status.
Specimen part, Subject
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