Filters
Technology
Platform
GSE18811
Homo sapiens
30 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The retinal pigment epithelium (RPE) is a polarized cell layer that is critical for photoreceptor function and survival. Its unique relationship to the photoreceptors and its specific physiology makes the RPE a critical determinant of human vision. Therefore we performed global expression profiling of native and cultured human fetal and adult RPE and determined a unique set of highly-expressed genes (called the signature set) by comparing the observed RPE gene profiles to the Novartis expression database (SymAtlas: http://wombat.gnf.org/index.html) of 78 tissues.
Publication Title
Transcriptome analysis and molecular signature of human retinal pigment epithelium.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 394 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Asthma is caused by a combination of poorly understood genetic and environmental factors. We found multiple markers on chromosome 17q21 to be strongly and reproducibly associated with childhood onset asthma in family and case-referent panels with a combined P < 10-12. In independent replication studies the 17q21 locus showed strong association with diagnosis of childhood asthma in 2,320 subjects from a cohort of German children (P = 0.0003) and in 3,301 subjects from the British 1958 Birth Cohort (P = 0.0005). We systematically evaluated the relationships between markers of the 17q21 locus and transcript levels of genes in EBV-transformed lymphoblastoid cell lines from children in the asthma family panel used in our association study. The SNPs associated with childhood asthma were consistently and strongly associated (P <10-22) in cis with transcript levels of ORMDL3, a member of a gene family that encode transmembrane proteins anchored in the endoplasmic reticulum. The results indicate that genetic variants regulating ORMDL3 expression are determinants of susceptibility to childhood asthma.
Publication Title
Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Reactivation of latent HCMV is a significant infectious complication of organ transplantation, and current therapies target viral replication once reactivation of transcriptionally silent, latent virus has already occurred. The specific molecular pathways that activate viral gene expression are not well understood. Our studies aim to identify these factors, with the goal of developing novel therapies that prevent transcriptional reactivation in transplant recipients. MCMV is a valuable model for studying latency and reactivation of CMV induced by organ transplantation. We previously demonstrated that transplantation of MCMV-latently infected kidneys into allogeneic recipients induces transcriptional reactivation of immediate early (IE) gene expression within 48 hr.
Publication Title
Transplant-induced reactivation of murine cytomegalovirus immediate early gene expression is associated with recruitment of NF-κB and AP-1 to the major immediate early promoter.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 46 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Immunosuppression is needed in HLA identical sibling renal transplantation. We conducted a tolerance trial in this patient cohort using Alemtuzumab induction, donor hematopoietic stem cells, tacrolimus/mycophenolate immunosuppression converted to sirolimus, planning complete drug withdrawal by 24 months post-transplantation. After an additional 12 months with no immunosuppression, normal biopsies and renal function, recipients were considered tolerant. Twenty recipients were enrolled. Of the first 10 (>36 months post-transplantation), 5 had immunosuppression successfully withdrawn for 16-36 months (tolerant), 2 had disease recurrence and 3 had subclinical rejection in protocol biopsies (non-tolerant). Microchimerism disappeared after 1 year, and CD4+CD25highCD127-FOXP3+ T cells and CD19+IgD/M+CD27- B cells increased to 5 years post-transplantation in both groups, whereas immune/inflammatory gene expression pathways in the peripheral blood and urine were differentially downregulated in tolerant compared to non-tolerant recipients. Therefore, in this HLA identical renal transplant tolerance trial, absent chimerism, Treg and Breg immunophenotypes were indistinguishable between tolerant and non-tolerant recipients, but global genomic changes indicating immunomodulation were observed only in tolerant recipients.
Publication Title
Genomic biomarkers correlate with HLA-identical renal transplant tolerance.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 38 Downloadable Samples
- Affymetrix Human Genome U95A Array (hgu95a)
Description
Gene expression analysis of a unique HNSCC (Head and Neck Squamous Cell Carcinoma) localization, the hypopharynx. Four normal and 34 tumor samples were analysed using Affymetrix HG-U95A microarrays containing probe sets representing ~12650 distinct transcription features.
Publication Title
Identification of genes associated with tumorigenesis and metastatic potential of hypopharyngeal cancer by microarray analysis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 115 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression has been proposed as an intermediate phenotype that can increase power in complex trait gene-mapping studies. Psoriasis, an immune-mediated, inflammatory and hyperproliferative disease of the skin and joints, provides an ideal model system to evaluate this paradigm, as conclusive evidence demonstrates that psoriasis has a genetic basis and the disease tissue is readily accessible.
Publication Title
Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 273 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Rationale: Interstitial fibrosis and tubular atrophy (IFTA) is found in ~25% of 1-year biopsies post-transplant(1, 2). It correlates with decreased graft survival when histological evidence of inflammation is present.(3-5) Identifying the etiology of IFTA is important because longterm graft survival has not changed as expected given improved therapies and a dramatically reduced incidence of acute rejection.(6-8) Methods: Gene expression profiles of 234 samples were obtained with matching clinical and outcome data (7 transplant centers). 81 IFTA samples were divided into subphenotypes by the degree of inflammation on histology: IFTA with acute rejection (AR), IFTA with inflammation and IFTA without inflammation. Samples with AR (n=54) and normally functioning transplants (TX; n=99) were used in comparisons. Conclusions: Gene expression profiling of all IFTA phenotypes were strongly enriched for cAR gene dysregulation pathways, including IFTA samples without histological evidence of inflammation. Thus, by molecular profiling we demonstrate that most IFTA samples have ongoing immune-mediated injury or chronic rejection that is more sensitively detected by gene expression profiling. We also found that the relative expression of AR-affiliated genes correlated with future graft loss in IFTA samples without inflammation. We conclude that undetected and/or undertreated immune rejection is leading to IFTA and graft failure.
Publication Title
Gene Expression in Biopsies of Acute Rejection and Interstitial Fibrosis/Tubular Atrophy Reveals Highly Shared Mechanisms That Correlate With Worse Long-Term Outcomes.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 656 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Development and clinical validity of a novel blood-based molecular biomarker for subclinical acute rejection following kidney transplant.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 529 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Sub-clinical acute rejection (subAR) in kidney transplant recipients (KTR) leads to chronic rejection and graft loss. Non-invasive biomarkers are needed to detect subAR. 307 KTR were enrolled into a multi-center observational study. Precise clinical phenotypes (CP) were used to define subAR. Differential gene expression (DGE) data from peripheral blood samples paired with surveillance biopsies were used to train a Random Forests (RF) model to develop a gene expression profile (GEP) for subAR. A separate cohort of paired samples was used to validate the GEP. Clinical endpoints and gene pathway mapping were used to assess clinical validity and biologic relevance. DGE data from 530 samples (130 subAR) collected from 250 KTR yielded a RF model: AUC 0.85; 0.84 after internal validation with bootstrap resampling. We selected a predicted probability threshold favoring specificity and NPV (87% and 88%) over sensitivity and PPV (64% and 61%, respectively). We tested the locked model/threshold on a separate cohort of 138 KTR undergoing surveillance biopsies at our institution (rejection 42; no rejection 96): NPV 78%; PPV 51%; AUC 0.66. Both the CP and GEP of subAR within the first 12 months following transplantation were independently associated with worse graft outcomes at 24 months, including de novo donor-specific antibody (DSA). Serial GEP tracked with response to treatment of subAR. DGE data from both cohorts mapped to gene pathways indicative of allograft rejection.
Publication Title
Development and clinical validity of a novel blood-based molecular biomarker for subclinical acute rejection following kidney transplant.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 127 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Sub-clinical acute rejection (subAR) in kidney transplant recipients (KTR) leads to chronic rejection and graft loss. Non-invasive biomarkers are needed to detect subAR. 307 KTR were enrolled into a multi-center observational study. Precise clinical phenotypes (CP) were used to define subAR. Differential gene expression (DGE) data from peripheral blood samples paired with surveillance biopsies were used to train a Random Forests (RF) model to develop a gene expression profile (GEP) for subAR. A separate cohort of paired samples was used to validate the GEP. Clinical endpoints and gene pathway mapping were used to assess clinical validity and biologic relevance. DGE data from 530 samples (130 subAR) collected from 250 KTR yielded a RF model: AUC 0.85; 0.84 after internal validation with bootstrap resampling. We selected a predicted probability threshold favoring specificity and NPV (87% and 88%) over sensitivity and PPV (64% and 61%, respectively). We tested the locked model/threshold on a separate cohort of 138 KTR undergoing surveillance biopsies at our institution (rejection 42; no rejection 96): NPV 78%; PPV 51%; AUC 0.66. Both the CP and GEP of subAR within the first 12 months following transplantation were independently associated with worse graft outcomes at 24 months, including de novo donor-specific antibody (DSA). Serial GEP tracked with response to treatment of subAR. DGE data from both cohorts mapped to gene pathways indicative of allograft rejection.
Publication Title
Development and clinical validity of a novel blood-based molecular biomarker for subclinical acute rejection following kidney transplant.
Sample Metadata Fields
No sample metadata fields
View Samples