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GSE65088
Homo sapiens
57 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Sepsis is a clinical syndrome that can be caused by bacteria or fungi. Early knowledge on the nature of the causative agent is a prerequisite for targeted anti-microbial therapy. Besides currently used detection methods like blood culture and PCR-based assays, the analysis of the transcriptional response of the host to infecting organisms holds great promise. In this study, we aim to examine the transcriptional footprint of infections caused by the bacterial pathogens Staphylococcus aureus and Escherichia coli and the fungal pathogens Candida albicans and Aspergillus fumigatus in a human whole-blood model. Moreover, we use the expression information to build a random forest classifier to determine if the pathogen is bacterial, fungal or neither of the two. After normalizing the transcription intensities using stably expressed reference genes, we filtered the gene set for biomarkers of bacterial or fungal blood infections. This selection is based on differential expression and an additional gene relevance measure. In this way, we identified 38 biomarker genes, including IL6, SOCS3, and IRG1 which were already associated to sepsis by other studies. Using these genes, we trained the classifier and assessed its performance. It yielded a 96% accuracy (sensitivities >93%, specificities >97%) for a 10-fold stratified cross-validation and a 92% accuracy (sensitivities and specificities >83%) for an additional dataset comprising Cryptococcus neoformans infections. Furthermore, the noise-robustness of the classifier suggests high rates of correct class predictions on datasets of new species. In conclusion, this genome-wide approach demonstrates an effective feature selection process in combination with the construction of a well-performing classification model. Further analyses of genes with pathogen-dependent expression patterns can provide insights into the systemic host responses, which may lead to new anti-microbial therapeutic advances.
Publication Title
Biomarker-based classification of bacterial and fungal whole-blood infections in a genome-wide expression study.
Sample Metadata Fields
Sex, Specimen part, Subject, Time
View Samples- Triticum aestivum
- 12 Downloadable Samples
- Affymetrix Wheat Genome Array (wheat)
Description
This study compared the photosynthetic performance and the global gene expression of the winter hardy wheat Triticum aestivum cv Norstar grown under non-acclimated (NA) or cold-acclimated (CA) condition at either ambient CO2 or elevated CO2 (EC). CA Norstar maintained comparable light saturated and CO2 saturated rates of photosynthesis but lower quantum requirements for photosystem II and non photochemical quenching relative to NA plants even at EC. Neither NA nor CA plants were sensitive to feedback inhibition of photosynthesis at EC. Global gene expression using microarray combined with bioinformatics analysis revealed that genes affected by EC were 3 times higher in NA (1022 genes) compared to CA (372 genes) Norstar. The most striking effect was the down-regulation of genes involved in the plant defense responses in NA Norstar. In contrast, cold acclimation reversed this down regulation due to the cold induction of genes involved in plant pathogenesis resistance, and cellular and chloroplast protection. These results suggest that EC have less impact on plant performance and productivity in cold adapted winter hardy plants in the northern climates compared to warmer environments. Selection for cereal cultivars with constitutively higher expression of biotic stress defense genes may be necessary under EC during the warm growth period and in warmer climates.
Publication Title
Long-term growth under elevated CO2 suppresses biotic stress genes in non-acclimated, but not cold-acclimated winter wheat.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Failure of molecular chaperones to direct the correct folding of newly synthesized proteins leads to the accumulation of misfolded proteins in cells. HSPA4 is a member of the heat shock protein 110 family (HSP110) that acts as a nucleotide exchange factor of HSP70 chaperones. We found that the expression of HSPA4 is upregulated in murine hearts subjected to pressure overload and in failing human hearts. To investigate the cardiac function of HSPA4, Hspa4 knockout (KO) mice were generated and exhibited cardiac hypertrophy and fibrosis. Hspa4 KO hearts were characterized by a significant increase in heart weight/body weight ratio, elevated expression of hypertrophic and fibrotic gene markers, and concentric hypertrophy with preserved contractile functions. Cardiac hypertrophy in Hspa4 KO hearts was associated with enhanced activation of gp130-STAT3, CaMKII, and calcineurin-NFAT signaling. Further analyses revealed a significant increase in cross sectional area of cardiomyocytes, and in expression levels of hypertrophic markers in cultured neonatal Hspa4 KO cardiomyocytes suggesting that the hypertrophy of mutant mice was a result of primary defects in cardiomyocytes. Gene expression profile in hearts of 3.5-week-old mice revealed a differentially expressed gene sets related to ion channels and stress response. Taken together, these results reveal that HSPA4 is implicated in protection against pressure overload-induced heart failure.
Publication Title
Targeted disruption of Hspa4 gene leads to cardiac hypertrophy and fibrosis.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Research in human immunobiology is mainly based on working with peripheral blood mononuclear cells (PBMC). However, recent investigations have shown that circulating CD4+ T cells are less sensitive to several T-cell activating monoclonal antibodies (mAb) and to recall antigens as compared to tissue-resident cells or cells that were in-vitro cultured at a high cell density of 10^7 cells/mL for 2 days at 37C and 5% CO2 (RESTORE protocol, Rmer et al., Blood 2011, PMID: 21931118). To explain the increase in sensitivity of CD4+ T-cells to mAbs and recall antigens on a molecular level, we performed microarray hybridizations of total RNA from T-cells isolated from PBMC that were cultured at a low or high cell density. To avoid the detection of genes that are up- or down-regulated by the culture process itself, we used low cell density cultured PBMC, instead of freshly prepared PBMC.
Publication Title
High-density preculture of PBMCs restores defective sensitivity of circulating CD8 T cells to virus- and tumor-derived antigens.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
IlluminaHiSeq2000
Description
In order to comprehensively identify RNA-expression changes after p53-activation, total RNA was isolated and subjected to next generation seqencing (RNA-Seq) after activation of a conditional p53 allele in SW480 cells. Overall design: SW480/pRTR-p53-VSV cells were subjected to RNA-Seq analysis after 48 hours doxycycline-treatment.
Publication Title
p53-Regulated Networks of Protein, mRNA, miRNA, and lncRNA Expression Revealed by Integrated Pulsed Stable Isotope Labeling With Amino Acids in Cell Culture (pSILAC) and Next Generation Sequencing (NGS) Analyses.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 44 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st), Affymetrix Mapping 250K Nsp SNP Array (mapping250knsp)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MRPL53, a New Candidate Gene for Orofacial Clefting, Identified Using an eQTL Approach.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 44 Downloadable Samples
Affymetrix Mapping 250K Nsp SNP Array (mapping250knsp), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
A valuable approach to understand how individual and population genetic differences can predispose to disease is to assess the impact of genetic variants on cellular functions (e.g., gene expression) of cell and tissue types related to pathological states. To understand the genetic basis of nonsyndromic cleft lip with or without cleft palate (NSCL/P) susceptibility, a complex and highly prevalent congenital malformation, we searched for genetic variants with a regulatory role in a disease-related tissue, the lip muscle (orbicularis oris muscle [OOM]), of affected individuals. From 46 OOM samples, which are frequently discarded during routine corrective surgeries on patients with orofacial clefts, we derived mesenchymal stem cells and correlated the individual genetic variants with gene expression from these cultured cells. Through this strategy, we detected significant cis-eQTLs (i.e., DNA variants affecting gene expression) and selected a few candidates to conduct an association study in a large Brazilian cohort (624 patients and 668 controls). This resulted in the discovery of a novel susceptibility locus for NSCL/P, rs1063588, the best eQTL for the MRPL53 gene, where evidence for association was mostly driven by the Native American ancestry component of our Brazilian sample. MRPL53 (2p13.1) encodes a 39S protein subunit of mitochondrial ribosomes and interacts with MYC, a transcription factor required for normal facial morphogenesis. Our study illustrates not only the importance of sampling admixed populations but also the relevance of measuring the functional effects of genetic variants over gene expression to dissect the complexity of disease phenotypes.
Publication Title
MRPL53, a New Candidate Gene for Orofacial Clefting, Identified Using an eQTL Approach.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Multiple myeloma (MM) is a clonal plasma cell disorder frequently accompanied by hematopoietic impairment. Genomic profiling of distinct HSPC subsets revealed a consistent deregulation of signaling cascades, including TGF beta signaling, p38MAPK signaling and pathways involved in cytoskeletal organization, migration, adhesion and cell cycle regulation in MM patients.
Publication Title
Multiple myeloma-related deregulation of bone marrow-derived CD34(+) hematopoietic stem and progenitor cells.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples