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SRP189204
Homo sapiens
19 Downloadable Samples
NextSeq 500
Description
Lymphatic malformation (LM) is a developmental anomaly of the lymphatic system that may lead to disfigurement, organ dysfunction and recurrent infection. Though several treatment modalities exist, pharmacotherapy is often associated with side effects and recurrence is common following surgical interventions. Moreover, despite the recent discovery of PIK3CA mutations in lymphatic endothelial cells of LM patients, the full spectrum of molecular pathways involved in LM pathogenesis is poorly understood. Here, we performed RNA sequencing on blood samples obtained from ten LM patients and nine healthy subjects and found 421 differentially expressed genes that stratify LM subjects from healthy controls. Using this LM gene signature, we identified novel pathway alterations in LM, such as oxidative phosphorylation, MEK/ERK, bone morphogenetic protein (BMP), and Wnt/b-catenin pathways, in addition to confirming the known alterations in cell cycle and the PI3K/AKT pathway. Furthermore, we performed computational drug repositioning analysis to predict existing therapies (e.g. sirolimus) and novel classes of drugs for LM. These findings deepen our understanding of LM pathogenesis and may facilitate non-invasive diagnosis, pathway analysis and therapeutic development. Overall design: RNA-sequencing of peripheral blooof 10 LM patients and 9 control subjects
Publication Title
Alterations of the MEK/ERK, BMP, and Wnt/β-catenin pathways detected in the blood of individuals with lymphatic malformations.
Sample Metadata Fields
Disease, Disease stage, Subject
View Samples- Homo sapiens
- 18 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Glucose intolerance and diabetes mellitus are classical parts of endogenous Cushings syndrome (CS), and insulin resistance is a feature of cortisol excess. CS patients display characteristics including hyperglycemia, abdominal obesity, reduced high-density lipoprotein cholesterol levels and elevated triglycerides, and arterial hypertension. Hypercortisolism is a well known cause of bone loss, and patients with CS frequently display low bone mass and fragility fractures. Cortisol excess inhibits bone formation, increases bone resorption, impairs calcium absorption from the gut, and affects the secretion of several hormones, cytokines, and growth factors with potential influence on bone metabolism. Bone biopsies from nine CS patients, before and mean 3 months after surgery, were screened for expressional candidate genes using Affymetrix human Gene Plus 2.0 Arrays. Analyses were performed to identify genes in glucocorticoid-induced osteoporosis and genes in glucose metabolism and energy homeostasis.
Publication Title
The glucocorticoid-induced leucine zipper gene (GILZ) expression decreases after successful treatment of patients with endogenous Cushing's syndrome and may play a role in glucocorticoid-induced osteoporosis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 21 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of the transcriptome of mouse models of prostate cancer. NP (Nkx3.1CreERT2/+; Ptenfloxed/floxed) mice develop non-metastatic tumors while NPK (Nkx3.1CreERT2/+; Ptenfloxed/floxed; KrasG12D/+) mice develop metastatic tumors
Publication Title
ETV4 promotes metastasis in response to activation of PI3-kinase and Ras signaling in a mouse model of advanced prostate cancer.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Mutant-IDH1-dependent chromatin state reprogramming, reversibility, and persistence.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 144 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We report here the genes that are sequentially expressed in white blood cells from blood and spleen at 2 hours, 2 day,3 days, and 7 days after burn and sham injury or trauma-hemorrhage (T-H) and sham T-H. Includes WBC treated with LPS for 2 hours and 1 day.
Publication Title
Comparison of longitudinal leukocyte gene expression after burn injury or trauma-hemorrhage in mice.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
Excessive consumption of beverages sweetened with high-fructose corn syrup (HFCS) is associated with obesity and with an increased risk of colorectal cancer. Whether HFCS contributes directly to tumorigenesis is unclear. We investigated the effects of daily oral administration of HFCS in APC mutant mice, which are predisposed to develop intestinal tumors. The HFCS-treated mice showed a dramatic increase in tumor size and tumor grade in the absence of obesity or metabolic syndrome. HFCS increased the levels of fructose and glucose in the intestinal lumen and serum, respectively, and the tumors absorbed both sugars. Within the tumors, fructose was converted to fructose-1-phosphate, leading to activation of glycolysis and increased synthesis of fatty acids that support tumor growth. These mouse studies support the hypothesis that the combination of dietary glucose and fructose, even at a moderate dose, can enhance tumorigenesis. Overall design: We investigated tumor and small intestines in APC mutant mice, which are predisposed to develop intestinal tumors.
Publication Title
High-fructose corn syrup enhances intestinal tumor growth in mice.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 31 Downloadable Samples
- Illumina HiSeq 2500
Description
Small intestinal bacterial overgrowth (SIBO) has been implicated in symptoms associated with functional gastrointestinal disorders (FGIDs), though mechanisms remain poorly defined and treatment involves non-specific antibiotics. Here we show that SIBO based on duodenal aspirate. culture reflects an overgrowth of anaerobes, does not correspond with patient symptoms, and may be a result of dietary preferences. Small intestinal microbial composition, on the other hand, is significantly altered in symptomatic patients and does not correspond with aspirate culture results. In a pilot interventional study we found that switching from a high fiber diet to a low fiber, high simple sugar diet triggered FGID-related symptoms and decreased small-intestinal microbial diversity and small-intestinal permeability. Our findings demonstrate that characterizing small intestinal microbiomes in patients with gastrointestinal symptoms may allow a more targeted antibacterial or a diet-based approach to treatment. Overall design: A host duodenal RNA sequencing study in conjuction with a microbial analysis of small bowel aspirates following dietary intervention to reduce fiber intake for 1 week. Aspirates were collected during research endoscopy and submtttied for for 16S microbial identification (european
Publication Title
Small intestinal microbial dysbiosis underlies symptoms associated with functional gastrointestinal disorders.
Sample Metadata Fields
Sex, Age, Specimen part, Disease stage, Subject, Time
View Samples- Homo sapiens
- 14 Downloadable Samples
- NextSeq 500
Description
Diamond-Blackfan anemia (DBA) is a rare bone marrow failure disorder that affects 7 out of 1,000,000 live births and has been associated with mutations in components of the ribosome. In order to characterize the genetic landscape of this heterogeneous disorder, we recruited a cohort of 472 individuals with a clinical diagnosis of DBA and performed whole exome sequencing (WES). We identified rare and predicted damaging mutations in likely causal genes for 78% of individuals. The majority of mutations were singletons, absent from population databases, predicted to cause loss of function, and in one of 19 previously reported ribosomal protein (RP) encoding genes. Using exon coverage estimates, we identified and validated 31 deletions in RP genes. We also observed an enrichment for extended splice site mutations and validated their diverse effects using RNA sequencing in individual-derived cell lines. Leveraging the size of our cohort, we observed robust genotype-phenotype associations with congenital abnormalities and treatment outcomes. We further identified rare mutations in 7 previously unreported RP genes that may cause DBA, as well as several distinct disorders that appear to phenocopy DBA, including 9 individuals with biallelic CECR1 mutations that result in deficiency of ADA2. However, no new genes were identified at exome-wide significance, suggesting that there are no unidentified genes containing mutations readily identified by WES that explain > 5% of DBA cases. Overall, this report should not only inform clinical practice for DBA individuals, but also the design and analysis of rare variant studies for heterogeneous Mendelian disorders. Overall design: 9 individuals with DBA with putative splice mutations and 5 control individuals were processed for RNA-seq.
Publication Title
The Genetic Landscape of Diamond-Blackfan Anemia.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples