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Mus musculus, Homo sapiens
321 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Staphylococcus aureus causes a spectrum of human infection. Diagnostic delays and uncertainty lead to treatment delays and inappropriate antibiotic use. A growing literature suggests the hosts inflammatory response to the pathogen represents a potential tool to improve upon current diagnostics. The hypothesis of this study is that the host responds differently to S. aureus than to E. coli infection in a quantifiable way, providing a new diagnostic avenue. This study uses Bayesian sparse factor modeling and penalized binary regression to define peripheral blood gene-expression classifiers of murine and human S. aureus infection. The murine-derived classifier distinguished S. aureus infection from healthy controls and Escherichia coli-infected mice across a range of conditions (mouse and bacterial strain, time post infection) and was validated in outbred mice (AUC>0.97). A S. aureus classifier derived from a cohort of 95 human subjects distinguished S. aureus blood stream infection (BSI) from healthy subjects (AUC 0.99) and E. coli BSI (AUC 0.82). Murine and human responses to S. aureus infection share common biological pathways, allowing the murine model to classify S. aureus BSI in humans (AUC 0.84). Both murine and human S. aureus classifiers were validated in an independent human cohort (AUC 0.95 and 0.94, respectively). The approach described here lends insight into the conserved and disparate pathways utilized by mice and humans in response to these infections. Furthermore, this study advances our understanding of S. aureus infection; the host response to it; and identifies new diagnostic and therapeutic avenues.
Publication Title
Gene expression-based classifiers identify Staphylococcus aureus infection in mice and humans.
Sample Metadata Fields
Race
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix HT MG-430 PM Array Plate (htmg430pm)
Description
Recent observations about how cells sense amino acids have argued for preeminent roles of mTOR and the stress kinase GCN2 in allowing cells to estimate their amino acid needs. Here we used models of programmed immune microenvironments where helper T cells have to sense how much amino acids are available to engage in antigen-fueled proliferation. Contrary to current models, T cells activate mTOR in the competency phase of the cell cycle regardless of amino acid amounts, GCN2 or surface TCR. Instead, we found T cells use an amino acid sensing system to target IL-2-induced STAT5 phosphorylation at the restriction point of cell cycle commitment. mTOR activity is subsequently reduced and specifically connected to SREBP activation. T cells can be pushed into cycle by increasing IL-2 even when no amino acids are available. Collectively, our studies reveal helper T cells use sequential and distinct pathways to measure local amino acid concentrations.
Publication Title
Proliferating Helper T Cells Require Rictor/mTORC2 Complex to Integrate Signals from Limiting Environmental Amino Acids.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 268 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The transcriptional responses of human hosts towards influenza viral pathogens are important for understanding virus-mediated immunopathology. Despite great advances gained through studies using model organisms, the complete temporal host transcriptional responses in a natural human system are poorly understood. In a human challenge study using live influenza (H3N2/Wisconsin) viruses, we conducted a clinically uninformed (unsupervised) factor analysis on gene expression profiles and established an ab initio molecular signature that strongly correlates to symptomatic clinical disease. This is followed by the identification of 42 biomarkers whose expression patterns best differentiate early from late phases of infection. In parallel, a clinically informed (supervised) analysis revealed over-stimulation of multiple viral sensing pathways in symptomatic hosts and linked their temporal trajectory with development of diverse clinical signs and symptoms. The resultant inflammatory cytokine profiles were shown to contribute to the pathogenesis because their significant increase preceded disease manifestation by 36 hours. In subclinical asymptomatic hosts, we discovered strong transcriptional regulation of genes involved in inflammasome activation, genes encoding virus interacting proteins, and evidence of active anti-oxidant and cell-mediated innate immune response. Taken together, our findings offer insights into influenza virus-induced pathogenesis and provide a valuable tool for disease monitoring and management in natural environments.
Publication Title
Temporal dynamics of host molecular responses differentiate symptomatic and asymptomatic influenza a infection.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Integrins facilitate intercellular movement and communication. Unlike the promiscuous activities of many integrins, 6 integrin is restricted to epithelia and partners exclusively with integrin V to modulate acute lung injury (ALI). Given that ALI is a complication of respiratory infection, we used mice lacking 6 integrin (6 KO) to probe the role of the epithelial layer in controlling the lung microenvironment during infection. We found 6 KO mice were protected from disease caused by influenza and Sendai virus infections. They were also protected from disease caused by Streptococcus pneumoniae infection alone and after prior influenza virus infection, the co-infection representing an often-lethal condition in humans. Resistance in the absence of epithelial 6 integrin was caused by intrinsic priming of the lung microenvironment by type I interferons through a mechanism involving transforming growth factor- regulation. Expression of 6 on epithelia suppresses the production of interferons, providing an advantage to the pathogen. Acute inhibition of 6 function may therefore provide a means to improve outcomes in lung microbial infections.
Publication Title
An Epithelial Integrin Regulates the Amplitude of Protective Lung Interferon Responses against Multiple Respiratory Pathogens.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 4 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
Long term exposure to incretin hormones is known to have salutory effects on beta cell function and viability. While short-term cAMP induction is known to have a signature CREB-CRTC target gene response, the long-term effects of cAMP on beta cell gene expression are less well understood.
Publication Title
mTOR links incretin signaling to HIF induction in pancreatic beta cells.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 113 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Diagnosis of acute respiratory viral infection is currentlybased on clinical symptoms and pathogen detection. Use of host peripheral blood gene expression data to classify individuals with viral respiratory infection represents a novel means of infection diagnosis.
Publication Title
Gene expression signatures diagnose influenza and other symptomatic respiratory viral infections in humans.
Sample Metadata Fields
Subject, Time
View Samples- Homo sapiens
- 647 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Diagnosis of influenza A infection is currently based on clinical symptoms and pathogen detection. Use of host peripheral blood gene expression data to classify individuals with influenza A virus infection represents a novel approach to infection diagnosis
Publication Title
A host transcriptional signature for presymptomatic detection of infection in humans exposed to influenza H1N1 or H3N2.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 277 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
A pressing clinical challenge is identifying the etiologic basis of acute respiratory illness. Without reliable diagnostics, the uncertainty associated with this clinical entity leads to a significant, inappropriate use of antibacterials. Use of host peripheral blood gene expression data to classify individuals with bacterial infection, viral infection, or non-infection represents a complementary diagnostic approach.
Publication Title
Host gene expression classifiers diagnose acute respiratory illness etiology.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
The results of this study indicate that stenotic fibroblasts exhibit an aberrant response to tissue stiffness with reduced MMP activity, leading to a perpetuous vicious circle of ever more fibrosis formation. Altering the microenvironment by LOX inhibition increases MMP activity and decreases ECM contraction, resulting in a potential anti-fibrotic agent for Crohns disease.
Publication Title
Fibrostenotic Phenotype of Myofibroblasts in Crohn's Disease is Dependent on Tissue Stiffness and Reversed by LOX Inhibition.
Sample Metadata Fields
Sex, Specimen part, Disease, Subject
View Samples
GSE18497- Homo sapiens
- 81 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Almost a quarter of pediatric patients with Acute Lymphoblastic Leukemia (ALL) suffer from relapses. The biological mechanisms underlying therapy response and development of relapses have remained unclear. In an attempt to better understand this phenomenon, we have analyzed 41 matched diagnosis relapse pairs of ALL patients using genomewide expression arrays (82 arrays) on purified leukemic cells. In roughly half of the patients very few differences between diagnosis and relapse samples were found (stable group), suggesting that mostly extra-leukemic factors (e.g., drug distribution, drug metabolism, compliance) contributed to the relapse. Therefore, we focused our further analysis on 20 samples with clear differences in gene expression (skewed group), reasoning that these would allow us to better study the biological mechanisms underlying relapsed ALL. After finding the differences between diagnosis and relapse pairs in this group, we identified four major gene clusters corresponding to several pathways associated with changes in cell cycle, DNA replication, recombination and repair, as well as B cell developmental genes. We also identified cancer genes commonly associated with colon carcinomas and ubiquitination to be upregulated in relapsed ALL. Thus, about half of relapses are due to selection or emergence of a clone with deregulated expression of a genes involved in pathways that regulate B cell signaling, development, cell cycle, cellular division and replication.
Publication Title
Genome-wide expression analysis of paired diagnosis-relapse samples in ALL indicates involvement of pathways related to DNA replication, cell cycle and DNA repair, independent of immune phenotype.
Sample Metadata Fields
Sex, Specimen part, Disease
View Samples