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GSE36059
Homo sapiens
391 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Histologic diagnosis of T cell-mediated rejection in kidney transplant biopsies has limited reproducibility because it is based on non-specific lesions using arbitrary rules that are subject to differing interpretations. We used microarray results from 403 indication biopsies previously given histologic diagnoses to develop a molecular classifier that assigned a molecular T cell-mediated rejection score to each biopsy. Independent assessment of the biopsies by multiple pathologists confirmed considerable disagreement on the presence of TCMR features: 79-88% accuracy and 35-69% sensitivity. The agreement of the molecular T cell-mediated rejection score with the histology diagnosis was similar to agreement among individual pathologists: accuracy 89%, sensitivity 51%. However, the score also predicted the consensus among pathologists, being highest when all agreed. Many discrepancies between the scores and the histologic diagnoses were in situations where histology is unreliable e.g. scarred biopsies. The score correlated with histologic lesions and gene sets associated with T cell-mediated rejection. The transcripts most often selected by the classifier were expressed in effector T cells, dendritic cells, or macrophages or inducible by interferon-gamma. Thus the T cell-mediated rejection score offers an objective assessment of kidney transplant biopsies, predicting the consensus opinion among multiple pathologists, and offering insights into underlying disease mechanisms.
Publication Title
Molecular diagnosis of T cell-mediated rejection in human kidney transplant biopsies.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 304 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The authors report that in INTERCOM, a prospective international study of 300 kidney transplant biopsies, a microarray-based molecular score for T cell-mediated rejection changed the assessment of 26% of all biopsies, illustrating the potential of precision diagnostics to impact practice.
Publication Title
Potential impact of microarray diagnosis of T cell-mediated rejection in kidney transplants: The INTERCOM study.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 282 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Kidney transplants that develop dysfunction or proteinuria after one year post transplant are at considerable risk for progression to renal failure. Identifying the molecules associated with graft failure could potentially lead to interventions that would slow the progression of organ failure.
Publication Title
A molecular classifier for predicting future graft loss in late kidney transplant biopsies.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 76 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In deceased donor kidney transplantation, acute kidney injury (AKI) prioir to surgery is a major determinant of delayed graft function (DGF), but AKI is histologically silent and difficult to assess. We hypothesized that a molecular measurement of AKI would add power to conventional risk assessments to predict the early poor allograft function at first week post transplantation.
Publication Title
Comparing molecular assessment of implantation biopsies with histologic and demographic risk assessment.
Sample Metadata Fields
Specimen part
View Samples- Oryza sativa
- 48 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
Oryza sativa cv. Nipponbare was engineered to over-express a barley alanine aminotransferase (alaAT) gene using the promoter (OsANT1) from a rice aldehyde dehydrogenase gene that expresses in roots.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 41 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray analysis of human kidneys with acute kidney injury (AKI) has been limited because such kidneys are seldom biopsied. However, all kidney transplants experience AKI, and early kidney transplants without rejection are an excellent model for human AKI: they are screened to exclude chronic kidney disease, frequently biopsied, and have extensive follow-up. We used histopathology and microarrays to compare indication biopsies from 28 transplants with AKI to 11 pristine protocol biopsies of stable transplants. Kidneys with AKI showed increased expression of 394 injury-repair response associated transcripts, including many known epithelial injury molecules (e.g. ITGB6, LCN2), tissue remodeling molecules (e.g. VCAN), and inflammation molecules (S100A8, ITGB3). Many other genes also predict the phenotype, depending on statistical filtering rules, including AKI biomarkers as HAVCR1 and IL18. Most mouse orthologs of the top injury-repair transcripts were increased in published mouse AKI models. Pathway analysis of the injury-repair transcripts revealed similarities to cancer, development, and cell movement. The injury-repair transcript score AKI kidneys correlated with reduced function, future recovery, brain death, and need for dialysis, but not future graft loss. In contrast, histologic features of "acute tubular injury" did not correlate with function or with the molecular changes. Thus the injury-repair associated transcripts represent a massive coordinate injury-repair response of kidney parenchyma to AKI, similar to mouse AKI models, and provide an objective measure for assessing the severity of AKI in kidney biopsies and validation for the use of many AKI biomarkers.
Publication Title
Molecular phenotypes of acute kidney injury in kidney transplants.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 44 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
In this placebo-controlled randomized controlled trial, we tested whether remote ischemic preconditioning (RIPC) elicited by four 5-minute cycles of 300 mmHg of cuff inflation/deflation of the lower limb would reduce myocardial necrosis in isoflurane-anesthetized patients undergoing on-pump coronary artery bypass graft surgery. Secondary outcomes were the perioperative release of the biomarkers NTproBNP, hsCRP, S100, atrial transcriptional profiles, and short- and long-term clinical outcomes. RIPC with concomitantly applied isoflurane did not affect the release of biomarkers or clinical outcome. NTproBNP release correlated with isoflurane- but not RIPC-induced transcriptional changes.
Publication Title
Remote ischemic preconditioning applied during isoflurane inhalation provides no benefit to the myocardium of patients undergoing on-pump coronary artery bypass graft surgery: lack of synergy or evidence of antagonism in cardioprotection?
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
Alternative splicing (AS) is a post-transcriptional gene regulatory mechanism that contributes to proteome diversity. Aberrant splicing mechanisms (mutations, polymorphisms, insertion/deletion etc.) contribute to various cancers and muscle related conditions such as Duchenne muscular dystrophy. However, dysregulation of AS in Cancer Cachexia (CC) patients remains unexplored. Our objectives were (i) to profile alternatively spliced genes (ASGs) on a genome-wide scale, and (ii) to identify DE alternatively spliced genes (DASGs) associated with CC. Rectus abdominis muscle biopsies obtained from cancer patients were stratified into cachectic cases (n=21, classified based on International consensus diagnostic framework for CC) and non-cachectic controls (n=19, weight stable cancer patients). Human Transcriptome array 2.0 was used for profiling ASGs using the total RNA isolated from muscle biopsies. Representative DASG signatures were validated using semi-quantitative RT-PCR. We identified 8960 ASGs, of which 922 DASGs (772 up-regulated, 150 down-regulated) were identified at > 1.4 fold-change and p < 0.05. Representative DASGs when validated by semi-quantitative RT-PCR also showed similar trends, confirming the primary findings from the genome-wide arrays. Identified DASGs were associated with myogenesis, adipogenesis, protein ubiquitination and inflammation. Up to 10% of the DASGs exhibited cassette exon (exon included or skipped) as a predominant form of AS event. We also observed other forms of AS events such as intron retention, alternate promoters. Overall, we have, for the first time conducted global profiling of muscle tissue to identify DASGs associated with CC. The mechanistic roles of the identified DASGs in CC pathophysiology using model systems is warranted, as well as replication of findings in independent cohorts.
Publication Title
Small RNAome profiling from human skeletal muscle: novel miRNAs and their targets associated with cancer cachexia.
Sample Metadata Fields
Specimen part
View Samples- Oryza sativa
- 31 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
Oryza sativa cv. Nipponbare was engineered to over-express a barley alanine aminotransferase (alaAT) gene using the promoter (OsANT1) from a rice aldehyde dehydrogenase gene that expresses in roots.
Publication Title
Transcriptome analysis of nitrogen-efficient rice over-expressing alanine aminotransferase.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
While prion infections have been extensively characterized in the laboratory mouse, little is known regarding the molecular responses to prions in other rodents. To explore these responses and make comparisons, we generated a prion disease in the laboratory rat by successive passage of mouse RML prions. Here we describe the accumulation of prions and associated pathology in the rat and describe the transcriptional impact throughout prion disease. Comparative transcriptional profiling between laboratory mice and rats suggests that similar molecular processes are unfolding in response to prion infection. At the level of individual transcripts, however, variability exists between mice and rats and many genes deregulated in mouse scrapie are not affected in rats. Notwithstanding these differences, many transcriptome responses are conserved between mice and rats infected with scrapie. Our findings highlight the usefulness of comparative approaches to understanding neurodegeneration and prion diseases in particular.
Publication Title
Transcriptomic responses to prion disease in rats.
Sample Metadata Fields
Specimen part, Disease
View Samples