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GSE13904
Homo sapiens
191 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Normal children, children with SIRS, children with sepsis, and children with septic shock.
Publication Title
Genomic expression profiling across the pediatric systemic inflammatory response syndrome, sepsis, and septic shock spectrum.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 130 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Septic shock is a heterogeneous syndrome within which probably exist several biological subclasses. Discovery and identification of septic shock subclasses could provide the foundation for the design of more specifically targeted therapies. Herein we tested the hypothesis that pediatric septic shock subclasses can be discovered through genome-wide expression profiling. Methods: Genome-wide expression profiling was conducted using whole blood-derived RNA from 98 children with septic shock, followed by a series of bioinformatic approaches targeted at subclass discovery and characterization. Results: Three putative subclasses (subclasses A, B, and C) were initially identified based on an empiric, discovery-oriented expression filter and unsupervised hierarchical clustering. Statistical comparison of the 3 putative subclasses (ANOVA, Bonferonni correction, p < 0.05) identified 6,934 differentially regulated genes. K means clustering of these 6,934 genes generated 10 coordinately regulated gene clusters corresponding to multiple signaling and metabolic pathways, all of which were differentially regulated across the 3 subclasses. Leave one out cross validation procedures indentified 100 genes having the strongest predictive values for subclass identification. Forty-four of these 100 genes corresponded to signaling pathways relevant to the adaptive immune system and glucocorticoid receptor signaling, the majority of which were repressed in subclass A patients. Subclass A patients were also characterized by repression of genes corresponding to zinc-related biology. Phenotypic analyses revealed that subclass A patients were younger, had a higher illness severity, and a higher mortality rate than patients in subclasses B and C. Conclusions: Genome-wide expression profiling can identify pediatric septic shock subclasses having clinically relevant phenotypes.
Publication Title
Identification of pediatric septic shock subclasses based on genome-wide expression profiling.
Sample Metadata Fields
Age, Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 114 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A gene expression atlas of early craniofacial development.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 55 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Goal of the experiment: To identify correlated genes, pathways and groups of patients with systemic inflammatory response syndrome and septic shock that is indicative of biologically important processes active in these patients.
Publication Title
Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 110 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gene expression signature for biliary atresia and a role for interleukin-8 in pathogenesis of experimental disease.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 103 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Septic shock heterogeneity has important implications for the conduct of clinical trials and individual patient management. We previously addressed this heterogeneity by indentifying 3 putative subclasses of children with septic shock based on a 100-gene expression signature corresponding to adaptive immunity and glucocorticoid receptor signaling. Herein we attempted to prospectively validate the existence of these gene expression-based subclasses in a validation cohort. Methods: Gene expression mosaics were generated from the 100 class-defining genes for 82 individual patients in the validation cohort. Patients were classified into 1 of 3 subclasses (A, B, or C) based on color and pattern similarity relative to reference mosaics generated from the original derivation cohort. Separate classifications were conducted by 21 individual clinicians and a computer-based algorithm. After subclassification the clinical database was mined for clinical phenotyping. Results: In the final consensus subclassification generated by clinicians, subclass A patients had a higher illness severity, as measured by illness severity scores and maximal organ failure, relative to subclasses B and C. The k coefficient across all possible inter-evaluator comparisons was 0.633. Similar observations were made based on the computer-generated subclassification. Patients in subclass A were also characterized by repression of a large number of genes having functional annotations related to zinc biology. Conclusions: We have validated the existence of subclasses of children with septic shock based on a biologically relevant, 100-gene expression signature. The subclasses can be indentified by clinicians without formal bioinformatics training, at a clinically relevant time point, and have clinically relevant phenotypic differences.
Publication Title
The influence of developmental age on the early transcriptomic response of children with septic shock.
Sample Metadata Fields
Age, Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 103 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We present a gene expression atlas of early mouse craniofacial development. Laser capture microdissection (LCM) was used to isolate cells from the principal critical micro-regions, whose development, differentiation and signaling interactions are responsible for the construction of the mammalian face.
Publication Title
A gene expression atlas of early craniofacial development.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 92 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Liver biopsy samples were obtained from 64 infants with biliary atresia at the time of intraoperative cholangiogram. Liver biopsy samples were obtained from 14 age-matched infants with other causes of intrahepatic cholestasis, and from 7 deceased-donor children. GeneChip Human Gene 1.0 ST Array (Affymetrix, CA) were used to screen mRNAs whose expression was specifically regulated in the livers from patients with biliary atresia.
Publication Title
Gene expression signature for biliary atresia and a role for interleukin-8 in pathogenesis of experimental disease.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 85 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Understanding biological pathways critical for common neurofibromatosis type 1 (NF1) peripheral nerve tumors is essential, as tumor biomarkers, prognostic factors and therapeutics are all lacking. We used gene expression profiling to define transcriptional changes between primary normal Schwann cells (n = 10), NF1-derived primary benign neurofibroma Schwann cells (n = 22), malignant peripheral nerve sheath tumor (MPNST) cell lines (n = 13), benign neurofibromas (n = 26) and MPNST (n = 6). Dermal and plexiform neurofibromas were indistinguishable. A prominent theme in the analysis was aberrant differentiation. Neurofibromas repressed gene programs normally active in Schwann cell precursors and immature Schwann cells. MPNST signatures strongly differed; genes upregulated in the sarcomas were significantly enriched for genes activated in neural crest cells. We validated differential expression of 82 genes including the neural crest transcription factor SOX9 and SOX9 predicted targets. SOX9 immunoreactivity was robust in neurofibroma and MPSNT tissue sections and targeting SOX9 - strongly expressed in NF1-related tumors - caused MPNST cell death. SOX9 is a biomarker of neurofibroma and MPNST, and possibly a therapeutic target in NF1.
Publication Title
Integrative genomic analyses of neurofibromatosis tumours identify SOX9 as a biomarker and survival gene.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 83 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Neurofibromatosis Type 1 (NF1) patients develop benign neurofibromas and malignant peripheral nerve sheath tumors (MPNST). These incurable peripheral nerve tumors result from loss of NF1 tumor suppressor gene function, causing hyperactive Ras signaling. Activated Ras controls numerous downstream effectors, but specific pathways mediating effects of hyperactive Ras in NF1 tumors are unknown. Cross-species transcriptome analyses of mouse and human neurofibromas and MPNSTs identified global negative feedback of genes that regulate Ras-Raf- MEK- extracellular signal-regulated protein kinase (ERK) signaling in both species. Nonetheless, activation of ERK was sustained in mouse and human neurofibromas and MPNST. PD0325901, a highly selective pharmacological inhibitor of MEK, was used to test whether sustained Ras-Raf-MEK-ERK signaling contributes to neurofibroma growth in the Nf1fl/fl;Dhh-cre mouse model or in NF1 patient MPNST cell xenografts. PD0325901 treatment reduced aberrantly proliferating cells in neurofibroma and MPNST, prolonged survival of mice implanted with human MPNST cells, and shrank neurofibromas in >80% of mice tested. PD0325901 also caused effects on tumor vasculature. Our data demonstrate that deregulated Ras/ERK signaling is critical for the growth of NF1 peripheral nerve tumors and provide strong rationale for testing MEK inhibitors in NF1 clinical trials.
Publication Title
MEK inhibition exhibits efficacy in human and mouse neurofibromatosis tumors.
Sample Metadata Fields
Specimen part
View Samples