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GSE32140
Mus musculus, Homo sapiens
99 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Plasticity and virus specificity of the airway epithelial cell immune response during respiratory virus infection.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 99 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To study the transcriptional profile of patients with acute RSV or Influenza infection,children of median age 2.4 months (range 1.5-8.6) hospitalized with acute RSV and influenza virus infection were offered study enrollment after microbiologic confirmation of the diagnosis. Blood samples were collected from them within 42-72 hours of hospitalization. We excluded children with suspected or proven polymicrobial infections, with underlying chronic medical conditions (i.e congenital heart disease, renal insufficiency), with immunodeficiency, or those who received systemic steroids or other immunomodulatory therapies. The RSV cohort consisted of 51 patients with median age of 2 months (range 1.5-3.9) and the influenza cohort had 28 patients with median age of 5.5 months (range 1.4-21). Control samples were obtained from healthy children undergoing elective surgical procedures or at outpatient clinic visits. To exclude viral co-infections we performed nasopharyngeal viral cultures of all subjects. We recruited 10 control patients for the RSV cohort with median age of 6.7 months (range 5-10), and 12 control patients for the influenza cohort with median age of18.5 months (range 10.5-26).
Publication Title
Plasticity and virus specificity of the airway epithelial cell immune response during respiratory virus infection.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 108 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Staphylococcus aureus has emerged as a significant pathogen causing severe, invasive disease in otherwise healthy people. Despite considerable advances in understanding the epidemiology, resistance mechanisms, and virulence factors produced by the bacteria, there is limited knowledge of the in vivo host immune response to acute, invasive S. aureus infections. Herein, we report that peripheral blood mononuclear cells from patients with severe S. aureus infections demonstrate a distinctive and robust gene expression profile which is validated in a distinct group of patients and on a different microarray platform. Application of a systems-wide modular analysis framework reveals significant over-expression of innate immunity genes and under-expression of genes related to adaptive immunity. Simultaneous flow cytometry analyses demonstrated marked alterations in immune cell numbers, with decreased central memory CD4 and CD8 T cells and increased number of monocytes. CD14+ monocyte numbers significantly correlated with the gene expression levels of genes related to the innate immune response. These results demonstrate the value of applying a systems biology approach that reveals the significant alterations in the components of circulating blood lymphocytes and monocytes in invasive S. aureus infections.
Publication Title
Enhanced monocyte response and decreased central memory T cells in children with invasive Staphylococcus aureus infections.
Sample Metadata Fields
Sex, Treatment, Race
View Samples- Homo sapiens
- 119 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Each infectious agent represents a unique combination of pathogen-associated molecular patterns that interact with specific pattern-recognition receptors expressed on immune cells. Therefore, we surmised that the blood immune cells of individuals with different infections might bear discriminative transcriptional signatures. Gene expression profiles were obtained for 131 peripheral blood samples from pediatric patients with acute infections caused by influenza A virus, Gram-negative (Escherichia coli) or Gram-positive (Staphylococcus aureus and Streptococcus pneumoniae) bacteria. Thirty-five genes were identified that best discriminate patients with influenza A virus infection from patients with either E coli or S pneumoniae infection. These genes classified with 95% accuracy (35 of 37 samples) an independent set of patients with either influenza A, E coli, or S pneumoniae infection. A different signature discriminated patients with E coli versus S aureus infections with 85% accuracy (34 of 40). Furthermore, distinctive gene expression patterns were observed in patients presenting with respiratory infections of different etiologies. Thus, microarray analyses of patient peripheral blood leukocytes might assist in the differential diagnosis of infectious diseases.
Publication Title
Gene expression patterns in blood leukocytes discriminate patients with acute infections.
Sample Metadata Fields
Sex, Age, Treatment, Race
View Samples- Homo sapiens
- 162 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The diagnosis of Kawasaki disease (KD) is often difficult to distinguish from adenovirus (HAdV) and Group A streptococcal disease (GAS). We sought to: 1) to define the KD transcriptional signature that can aid in the diagnosis of complete and incomplete KD in children; 2) to identify specific biomarkers that objectively discriminate between KD and other mimicking conditions, including HAdV and 3) to test the prognostic utility of GEP to determine response to IVIG therapy and development of coronary artery lesions (CAL). Methods: Blood RNA samples were analyzed from 76 pediatric patients with complete KD, 13 with incomplete KD, 19 patients with HAdV, 17 patients with GAS disease, and age- and sex-matched healthy controls (HC). We used class comparisons (MW p< 0.01, Benjamini-Hochberg, and 1.25 fold change filter), class prediction, modular analysis and MDTH analyses to define the specificity of the KD profiles and identify markers of severity. Results: Statistical group comparisons identified 7,899 genes differentially expressed in 39 complete KD patients versus HC (KD biosignature). This signature was validated in another 37 patients with complete KD and in 13 patients with incomplete KD. Modular analysis in children with complete KD demonstrated overexpression of inflammation, neutrophils, myeloid cell, coagulation cascade, and cell cycle genes. The KNN class prediction algorithm identified 25-classifier genes that differentiated children with KD vs HAdV infection in two independent cohorts of patients with 96% (95% CI [80%-99%]) sensitivity and 95% [74%-99%] specificity. MDTH scores in KD patients significantly correlated with the baseline c-reactive protein (R=0.29, p=0.008) and was four fold higher than in children with HAdV (p<0.01). In addition, KD patients that remained febrile 36 hours after treatment with IVIG (non-responders) demonstrated higher baseline, pre-treatment MDTH values compared with responders [12,290 vs. 5,572 respectively; p=0.009]. Conclusion: Transcriptional signatures can be used as a tool to discriminate between KD and HAdV infection, and may also provide prognostic information.
Publication Title
Whole blood transcriptional profiles as a prognostic tool in complete and incomplete Kawasaki Disease.
Sample Metadata Fields
Sex, Specimen part, Race
View Samples- Homo sapiens
- 104 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Rationale: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections and hospitalizations in infants worldwide. Known risk factors, however, incompletely explain the variability of RSV disease severity among children. We postulate that severity of RSV infection is influenced in part by modulation of the host immune response by the local microbial ecosystem at the time of infection. Objectives: To define whether different nasopharyngeal microbiota profiles are associated with distinct host transcriptome profiles and severity in children with RSV infection. Methods: We analyzed the nasopharyngeal microbiota profiles of young children with mild and severe RSV disease and healthy matched controls by 16S-rRNA sequencing. In parallel, we analyzed whole blood gene expression profiles to study the relationship between microbial community composition, the RSV-induced host transcriptional response and clinical disease severity. Measurements and Main results: We identified five nasopharyngeal microbiota profiles characterized by enrichment of H. influenzae, Streptococcus, Corynebacterium, Moraxella or S. aureus. RSV infection and RSV hospitalization were positively associated with H. influenzae and Streptococcus, and negatively associated with S. aureus abundance, independent of age. The host response to RSV was defined by overexpression of interferon-related genes, and this was independent of the microbiota composition. On the other hand, transcriptome profiles of RSV infected children with H. influenzae and Streptococcus-dominated microbiota were characterized by greater overexpression of genes linked to toll-like receptor-signaling and neutrophil activation and were more frequently hospitalized Conclusions: Our data suggest an immunomodulatory role for the resident nasopharyngeal microbial community early in RSV infection, potentially affecting RSV disease severity.
Publication Title
Nasopharyngeal Microbiota, Host Transcriptome, and Disease Severity in Children with Respiratory Syncytial Virus Infection.
Sample Metadata Fields
Sex, Specimen part, Disease, Race
View Samples- Homo sapiens
- 74 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Background: There is limited data on how different RSV genotypes and associated viral loads influence disease phenotypes. We characterized the genetic variability of RSV strains during five non-consecutive respiratory seasons, and evaluated the role of RSV subtypes, genotypes and viral loads on clinical disease severity.
Publication Title
Respiratory Syncytial Virus Genotypes, Host Immune Profiles, and Disease Severity in Young Children Hospitalized With Bronchiolitis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 232 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Systemic onset Juvenile Idiopathic Arthritis (SoJIA) represents up to 20% of Juvenile Idiopathic Arthritis (JIA). We have previously reported that this disease is Interleukin 1 (IL1)-mediated, and that IL-1 blockade results in clinical remission in the majority of patients. The diagnosis of SoJIA, however, still relies on clinical findings as no specific diagnostic tests are available, which leads to delays in the initiation of specific therapy. To identify specific diagnostic markers, we analyzed gene expression profiles in 19 pediatric patients with SoJIA during the systemic phase of the disease (fever and/or arthritis), 25 SoJIA patients with no systemic symptoms (arthritis only or no symptoms), 39 healthy controls, 94 pediatric patients with acute viral and bacterial infections (available under GSE6269), 38 pediatric patients with Systemic Lupus Erythematosus (SLE), and 6 patients with a second IL-1 mediated disease known as PAPA syndrome. Statistical group comparison and class prediction identified genes differentially expressed in SoJIA patients compared to healthy children. These genes, however, were also changed in patients with acute infections and SLE. By performing an analysis of significance across all diagnostic groups, we generated a list of 88 SoJIA-specific genes (p<0.01 in SoJIA and >0.5 in all other groups). A subset of 12/88 genes permitted us to accurately classify an independent test set of SoJIA patients with systemic disease. We were also able to identify a group of transcripts that changed significantly in patients undergoing IL-1 blockade. Thus, analysis of transcriptional signatures from SoJIA blood leukocytes can help distinguishing this disease from other febrile illnesses and assessing response to therapy. Availability of accurate diagnostic markers for SoJIA patients may allow prompt initiation of effective therapy and prevention of long-term disabilities.
Publication Title
Blood leukocyte microarrays to diagnose systemic onset juvenile idiopathic arthritis and follow the response to IL-1 blockade.
Sample Metadata Fields
Sex, Age, Treatment, Race
View Samples- Homo sapiens
- 151 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Human rhinoviruses (HRV) are among the most common causes of respiratory infections in humans but can be frequently detected also in asymptomatic subjects. We evaluated the value of gene expression profiles to differentiate asymptomatic detection from symptomatic HRV infection in children.
Publication Title
Rhinovirus Detection in Symptomatic and Asymptomatic Children: Value of Host Transcriptome Analysis.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Race
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
The objectives of this study were to understand the effect of phenolic compounds from fermented berry beverages on hyperglycemia and obesity in vivo using mice fed a high fat diet. Our hypothesis was that consumption of a fermented blueberry-blackberry beverage and its phenolic compounds would reduce the development of obesity and hyperglycemia in diet-induced obese mice. Body composition, histomorphological analysis of pancreatic islets and liver, and expression of genes involved in obesity and hyperglycemia were evaluated in order to explain the modulation of diet-induced obesity and hyperglycemia due to treatments.
Publication Title
Alcohol-free fermented blueberry-blackberry beverage phenolic extract attenuates diet-induced obesity and blood glucose in C57BL/6J mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples