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GSE68004
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
- 114 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Rationale: Despite shortening vasopressor use in shock, hydrocortisone administration remains controversial, with potential harm on the immune system. Few studies assessed hydrocortisone impact on the transcriptional response in shock, and we are lacking data in burns. Objectives: To assess the hydrocortisone-induced transcriptional modulation in severe burn shock, particularly on the immune response. Methods: We collected whole blood samples (n= 117) during a randomized controlled trial assessing the efficacy of hydrocortisone administration on burn shock. Using whole genome microarrays, we first compared burn patients from the placebo group (n=15) to healthy volunteers (n=13) to describe the transcriptional modulation induced by burn shock over the first week. Then we compared burn patients randomized for either hydrocortisone administration (n=15) or placebo (n=15) to assess hydrocortisone-induced modulation. Measurements and Main Results: Study groups were similar in terms of severity and major outcomes, but shock duration (significantly reduced in the hydrocortisone group). Many genes (n=2250) were differentially expressed between burn patients and healthy volunteers, with 85% of them exhibiting a profound and persistent modulation over seven days. Interestingly, we showed that hydrocortisone enhanced the shock-associated repression of adaptive, but also innate immunity. Conclusions: We found that the initial host response to burn shock encompasses a wide and persistent modulation of gene expression, with profound modulation of pathways associated with metabolism and immunity. Importantly, hydrocortisone administration may worsen the immunosuppression associated with severe injury. These data should be taken into account in the risk ratio of hydrocortisone administration in patients with inflammatory shock.
Publication Title
Transcriptome modulation by hydrocortisone in severe burn shock: ancillary analysis of a prospective randomized trial.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Treatment, Subject
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Severe septic syndromes deeply impair innate and adaptive immunity. While neutrophils represent the first line of defense against infection, little is known about their phenotype and functions during sepsis-induced immunosuppression. The objective of this study was thus to perform for the first time a global evaluation of neutrophil alterations in immunosuppressed septic patients based on phenotypic, functional and transcriptomic studies. In addition, the potential association of these parameters and deleterious outcomes was assessed.
Publication Title
Marked alterations of neutrophil functions during sepsis-induced immunosuppression.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 120 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Sepsis is a major health concern, with high morbidity and mortality workdwide. In order to identify prognostic biomarkers in septic shock patients, we performed a microarray study exploring the early modulation of gene expression according to day 28 mortality.
Publication Title
Modulation of LILRB2 protein and mRNA expressions in septic shock patients and after ex vivo lipopolysaccharide stimulation.
Sample Metadata Fields
Sex, Age, Time
View Samples- Mus musculus
- 21 Downloadable Samples
Illumina HiSeq 2500
Description
Renal artery stenosis (RAS) caused by narrowing of arteries is characterized by microvascular damage. Macrophages are implicated in repair and injury, but the specific populations responsible for these divergent roles have not been identified. Here, we characterized murine kidney F4/80+CD64+ macrophages in three transcriptionally unique populations. Using fate-mapping and parabiosis studies, we demonstrate that CD11b/cint are long-lived kidney-resident (KRM) while CD11chiMf, CD11cloMf are monocyte-derived macrophages. In a murine model of RAS, KRM self-renewed, while CD11chiMf and CD11cloMf increased significantly, which was associated with loss of peritubular capillaries. Replacing the native KRM with monocyte-derived KRM using bone marrow transplantation followed by RAS, amplified loss of peritubular capillaries. To further elucidate the nature of interactions between KRM and peritubular endothelial cells, we performed RNA-sequencing on flow-sorted macrophages from Sham and RAS kidneys. KRM showed a prominent activation pattern in RAS with significant enrichment in reparative pathways, like angiogenesis and wound healing. In culture, KRM increased proliferation of renal peritubular endothelial cells implying direct pro-angiogenic properties. Human homologs of KRM identified as CD11bintCD11cintCD68+ increased in post-stenotic kidney biopsies from RAS patients compared to healthy human kidneys, and inversely correlated to kidney function. Thus, KRM may play protective roles in stenotic kidney injury through expansion and upregulation of pro-angiogenic pathways Overall design: CD11chiMf Sham, n=3; CD11chiMf RAS, n=4; CD11cloMf Sham, n=3; CD11cloMf RAS, n=4; KRM Sham, n=4; KRM RAS, n=3;
Publication Title
Kidney-resident macrophages promote a proangiogenic environment in the normal and chronically ischemic mouse kidney.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
5-Fluorouracil (5-FU) is a widely used chemotherapeutic drug in colorectal cancer. Previous studies showed that 5-FU modulates RNA metabolism and mRNA expression. In addition, it has been reported that 5-FU incorporates into the RNAs constituting the translational machinery and that 5-FU affects the amount of some mRNAs associated with ribosomes. However, the impact of 5-FU on translational regulation remains unclear. Using translatome profiling, we report that a clinically relevant dose of 5-FU induces a translational reprogramming in colorectal cancer cell lines. Comparison of mRNA distribution between polysomal and non-polysomal fractions in response to 5-FU treatment using microarray quantification identified 313 genes whose translation was selectively regulated. These regulations were mostly stimulatory (91%). Among these genes, we showed that 5-FU increases the mRNA translation of HIVEP2, which encodes a transcription factor whose translation in normal condition is known to be inhibited by mir-155. In response to 5-FU, the expression of mir-155 decreases thus stimulating the translation of HIVEP2 mRNA. Interestingly, the 5-FU-induced increase in specific mRNA translation was associated with reduction of global protein synthesis. Altogether, these findings indicate that 5-FU promotes a translational reprogramming leading to the increased translation of a subset of mRNAs that involves at least for some of them, miRNA-dependent mechanisms. This study supports a still poorly evaluated role of translational control in drug response.
Publication Title
Translational reprogramming of colorectal cancer cells induced by 5-fluorouracil through a miRNA-dependent mechanism.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 26 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
While it is clear that T cell derived IFN has to act on tumor stroma cells for rejection of solid tumors, it is not clear which tumor stroma cells are targets. We studied how IFN affects gene expression in tumor blood vessels in vivo. To study the effect on endothelial cells, we either used a model of ectopic IFN (MCA313 tumors) or IFN-GFP fusion protein (J558L tumors) expression in tumors, or we used T cell derived IFN in large vascularized 16.113 tumours. Tumors were grown in mice that were expressing the IFN receptor ubiquitously (J558L tumors + IFN-GFP treatment and 16.113 tumors + T cell treatment) or in some experiments the IFN-receptor was expressed exclusively in endothelial cells (MCA313 tumor + IFN treatment).
Publication Title
Tumour ischaemia by interferon-γ resembles physiological blood vessel regression.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
A better understanding of molecular changes during oral tumorigenesis may help defining new personalized prevention strategies. In order to test this hypothesis, we analyzed whole-genome expression changes in a murine model of oral carcinogenesis, induced by an oral carcinogen (4-NQO)
Publication Title
The dynamics of gene expression changes in a mouse model of oral tumorigenesis may help refine prevention and treatment strategies in patients with oral cancer.
Sample Metadata Fields
Sex, Specimen part
View Samples