Filters
Technology
Platform
GSE57578
Homo sapiens
4 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
DCD is a gene amplified and overexpressed in a subset of breast tumors acting as a growth and survival factor. Patients with DCD-positive breast cancer have worse prognostic features. To investigate the role of DCD in breast tumorigenesis, we analyzed the consequences of its downregulation in human breast cancer cell lines using three specific shRNA lentivirus vectors. Genes up- and down-regulated by DCD were identified using Affymetrix microarray and analyzed by MetaCore Platform. We found that loss of DCD expression led to reduced cell proliferation, resistance to apoptosis, and suppressed tumorigenesis in immunodeficient mice. Network analysis of gene expression data revealed perturbed ERBB signaling following DCD shRNA expression including changes in the expression of ERBB receptors and their ligands. These findings imply that DCD promotes breast tumorigenesis via modulating the activity of the ERBB signaling pathways. As ERBB signaling is also important for neural survival, HER2+ breast tumors may highjack DCDs neural survival-promoting functions to promote tumorigenesis.
Publication Title
Dermcidin exerts its oncogenic effects in breast cancer via modulation of ERBB signaling.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 39 Downloadable Samples
- Sentrix Human-6 v2 Expression BeadChip
Description
Melioidosis is a severe infectious disease caused by Burkholderia pseudomallei, a gram-negative bacillus classified by the NIAID as a category B priority agent. Septicemia is the most common presentation of the disease with 40% mortality rate even with appropriate treatments. Faster diagnostic procedures are required to improve therapeutic response and survival rates. We have used microarray technology to generate genome-wide transcriptional profiles (>48,000 transcripts) of whole blood obtained from patients with septicemic melioidosis (n=32), patients with sepsis caused by other pathogens (n=31), and uninfected controls (n=29). Unsupervised analyses demonstrated the existence of a whole blood transcriptional signature distinguishing patients with sepsis from control subjects. The majority of changes observed were common to both septicemic melioidosis and sepsis caused by other infections, including genes related to inflammation, interferon-related genes, neutrophils, cytotoxic cells, and T cells. Finally, class prediction analysis identified a 37 transcript candidate diagnostic signature that distinguished melioidosis from sepsis caused by other organisms with 100% and 78% accuracy in training and independent test sets, respectively. This finding was confirmed by the independent validation set, which showed 80% prediction accuracy. This signature was highly enriched in genes coding for products involved in the MHC Class II antigen processing and presentation pathway. Transcriptional patterns of whole blood RNA distinguish patients with septicemic melioidosis from patients with sepsis caused by other pathogens. Once confirmed in a large scale trial this diagnostic signature might constitute the basis of a differential diagnostic assay.
Publication Title
Genomic transcriptional profiling identifies a candidate blood biomarker signature for the diagnosis of septicemic melioidosis.
Sample Metadata Fields
Sex, Age, Treatment, Race
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- Mus musculus
- 170 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Melioidosis, a severe human disease caused by the bacterium Burkholderia pseudomallei, has a wide spectrum of clinical manifestations ranging from acute septicaemia to chronic localized illness or latent infection. Mice were intranasally infected with either high or low doses of B. pseudomallei to generate either acute, chronic or latent infection and host blood and tissue transcriptional profiles were generated. Acute infection was accompanied by a homogeneous signature associated with induction of multiple innate immune response pathways, such as IL10, TREM1 and IFN-signaling, largely found in both blood and tissue. The transcriptional profile in blood reflected the heterogeneity of chronic infection and quantitatively reflected the severity of disease. Comparison of these mouse blood datasets by pathway and modular analysis with the blood transcriptional signature of patients with melioidosis showed that many genes were similarly perturbed, including IL10, TREM1 and IFNsignaling, revealing the common immune response occurring in both mice and humans.
Publication Title
The Blood Transcriptome of Experimental Melioidosis Reflects Disease Severity and Shows Considerable Similarity with the Human Disease.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Acute myeloid leukemia (AML) continues to have the lowest survival rates of all leukemias. Therefore, new therapeutic strategies are urgently needed to improve clinical outcomes for AML patients. Here, we report a novel role for Wilms’ tumor 1-associated protein (WTAP) in pathogenesis of AML. We have performed RNA-Seq in K562 cells with knockdown of WTAP to ascertain which genes it regulates. Overall design: We have 2 replicates of total RNA for K562 cells and 2 replicates with WTAP knocked down
Publication Title
WTAP is a novel oncogenic protein in acute myeloid leukemia.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 49 Downloadable Samples
Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Systems biology approaches reveal a specific interferon-inducible signature in HTLV-1 associated myelopathy.
Sample Metadata Fields
Sex, Age, Disease, Race
View Samples- Homo sapiens
- 39 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Infection with the human T lymphotropic virus type 1 (HTLV-1) remains asymptomatic in the majority of carriers; however, some 5% develop a chronic inflammation of the central nervous system termed HTLV-1-associated myelopathy (HAM). It is not well understood how the virus triggers the onset of HAM after many years of clinical latency and importantly, what distinguishes hosts who develop the disease from those who remain asymptomatic. In this study we tested the hypothesis that patients with HAM can be distinguished from asymptomatic HTLV-1 carriers (ACs) and uninfected subjects by their whole blood transcriptional profiles. Here, we compare unstimulated whole blood gene expression profiles of 20 asymptomatic HTLV-1 carriers (ACs), 10 patients with HAM and 9 uninfected healthy control subjects to (1) identify a transcriptional signature associated with presence of HAM and (2) identify cell types and pathways abnormally regulated in HAM by canonical and modular pathway analysis.
Publication Title
Systems biology approaches reveal a specific interferon-inducible signature in HTLV-1 associated myelopathy.
Sample Metadata Fields
Sex, Age, Disease, Race
View Samples- Homo sapiens
- 10 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Infection with the human T lymphotropic virus type 1 (HTLV-1) remains asymptomatic in the majority of carriers; however, some 5% develop a chronic inflammation of the central nervous system termed HTLV-1-associated myelopathy (HAM). It is not well understood how the virus triggers the onset of HAM after many years of clinical latency and importantly, what distinguishes hosts who develop the disease from those who remain asymptomatic. In a previous study we identified a 80-gene transcriptional signature of HAM based in the hypothesis that patients with HAM can be distinguished from asymptomatic HTLV-1 carriers (ACs) and uninfected subjects by their whole blood transcriptional profiles. In this study we wished to validate the 80-gene signature on an independent cohort comprising 17 asymptomatic HTLV-1 carriers (ACs), 10 patients with HAM and 8 uninfected healthy control subjects.
Publication Title
Systems biology approaches reveal a specific interferon-inducible signature in HTLV-1 associated myelopathy.
Sample Metadata Fields
Sex, Age, Disease, Race
View Samples- Homo sapiens
- 351 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip, Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptional specialization of human dendritic cell subsets in response to microbial vaccines.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 128 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip, Illumina HumanHT-12 V4.0 expression beadchip
Description
While dendritic cells (DCs) are known to play a major role in the process of vaccination, the mechanisms by which vaccines induce protective immunity in humans remain elusive. Herein, we used gene microarrays to characterize the transcriptional programs induced over time in human monocyte-derived DCs (moDCs) in vitro in response to influenza H1N1 Brisbane, Salmonella enterica and Staphylococcus aureus. We built a data-driven modular analytical framework focused on 204 pathogen-induced gene clusters. The expression of these modules was analyzed in response to 16 well-defined ligands, targeting TLRs, cytoplasmic PAMP receptors and cytokine receptors. This multi-dimensional framework covers the major biological functions of APC, including the IFN response, inflammation, DC maturation, T cell activation, antigen processing, cell motility and histone regulation. This framework was used to characterize the response of monocytes and moDCs to 14 commercially available vaccines. These vaccines displayed quantitatively and qualitatively distinct modular signatures in monocytes and DCs, in particular Fluzone and Pneumovax, highlighting the functional and phenotypic differences between APC subsets. This modular framework allows the application of systems immunology approaches to study early transcriptional changes in human APC subsets in response to pathogens and vaccines, which might guide the development of improved vaccines.
Publication Title
Transcriptional specialization of human dendritic cell subsets in response to microbial vaccines.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples