This dataset is composed of the unique patients (276; at the Day 1 timepoint) that are present in the six other GEO datasets published by Hector Wong and the Genomics of Pediatric SIRS and Septic Shock Investigators. This dataset thus includes all unique patients from GSE4607, GSE8121, GSE9692, GSE13904, GSE26378, and GSE26440. These are only from the Day 1 timepoint.
A comprehensive time-course-based multicohort analysis of sepsis and sterile inflammation reveals a robust diagnostic gene set.
Specimen part, Disease
View SamplesMitochondrial DNA (mtDNA) encodes essential components of the respiratory chain and loss of mtDNA leads to mitochondrial dysfunction and neurodegeneration. Mitochondrial transcription factor A (TFAM) is an essential component of mtDNA replication and a regulator of mitochondrial copy number in cells. Studies have shown that TFAM knockdown leads to mitochondrial dysfunction and respiratory chain deficiencies. ATP synthase is Complex V of the mitochondrial respiratory chain. It is driven by a proton gradient between the intermembrane space and the mitochondrial matrix and generates the majority of cellular ATP. The knockdown of coupling factor 6 (Cf6), one of the components of the proton channel F0, causes dysfunction in the complex, leading to mitochondrial dysfunction and respiratory chain deficiencies. Using gene expression analysis, we aimed to investigate the effects of mtDNA dysfunction in the CNS at the molecular level.
Mitochondrial retrograde signaling regulates neuronal function.
Specimen part
View SamplesThe earliest recognizable stages of breast neoplasia are lesions that represent a heterogeneous collection of epithelial proliferations currently classified based on morphology. Their role in the development of breast cancer is not well understood but insight into the critical events at this early stage will improve efforts in breast cancer detection and prevention. These microscopic lesions are technically difficult to study so very little is known about their molecular alterations. To characterize the transcriptional changes of early breast neoplasia, we sequenced 3''- end enriched RNAseq libraries from formalin-fixed paraffin-embedded tissue of early neoplasia samples and matched normal breast and carcinoma samples from 25 patients. We find that gene expression patterns within early neoplasias are distinct from both normal and breast cancer patterns and identify a pattern of pro-oncogenic changes, including elevated transcription of ERBB2, FOXA1, and GATA3 at this early stage. We validate these findings on a second independent gene expression profile data set generated by whole transcriptome sequencing. Measurements of protein expression by immunohistochemistry on an independent set of early neoplasias confirms that ER pathway regulators FOXA1 and GATA3, as well as ER itself, are consistently upregulated at this early stage. The early neoplasia samples also demonstrate coordinated changes in long non-coding RNA expression and microenvironment stromal gene expression patterns. This study is the first examination of global gene expression in early breast neoplasia, and the genes identified here represent candidate participants in the earliest molecular events in the development of breast cancer. Overall design: 3SEQ was performed on 72 FFPE human breast samples from 25 patients: 24 normal, 25 early neoplasia, 9 carcinoma in situ, and 14 invasive cancer
A shared transcriptional program in early breast neoplasias despite genetic and clinical distinctions.
Specimen part, Disease, Disease stage, Subject
View SamplesDifferent strains of T. brucei induce different degrees of pathology in infected animals, and TREU927-infected mice display greater splenomegaly and anaemia than 247-infected mice. The analysis of differential host gene expression in infected spleens has allowed the identification of which pathways or processes are crucial in determining the progression of disease, for example IL10, LXR/RXR activation and alternative macrophage activation.
Role for parasite genetic diversity in differential host responses to Trypanosoma brucei infection.
Specimen part
View SamplesBackground: The ZNF217 gene, encoding a C2H2 zinc finger protein, is located at 20q13 and found amplified and overexpressed in greater than 20% of breast tumors. Current studies indicate ZNF217 drives tumorigenesis, yet the regulatory mechanisms of ZNF217 are largely unknown. Because ZNF217 associates with chromatin modifying enzymes, we postulate that ZNF217 functions to regulate specific gene signaling networks. Here, we present a large-scale functional genomic analysis of ZNF217, which provides insights into the regulatory role of ZNF217 in MCF7 breast cancer cells. Results: ChIP-seq analysis reveals that the majority of ZNF217 binding sites are located at distal regulatory regions associated with the chromatin marks H3K27ac and H3K4me1. Analysis of ChIPseq transcription factor binding sites shows clustering of ZNF217 with FOXA1, GATA3 and ERalpha binding sites, supported by the enrichment of corresponding motifs for the ERalpha-associated cisregulatory sequences. ERalpha expression highly correlates with ZNF217 in lysates from breast tumors (n=15), and ERalpha co-precipitates ZNF217 and its binding partner CtBP2 from nuclear extracts. Transcriptome profiling following ZNF217 depletion identifies differentially expressed genes co-bound by ZNF217 and ERalpha; gene ontology suggests a role for ZNF217-ERalpha in expression programs associated with ER+ breast cancer studies found in the Molecular Signature Database. Data-mining of expression data from breast cancer patients correlates ZNF217 with reduced overall survival in multiple subtypes. Conclusions: Our genome-wide ZNF217 data suggests a functional role for ZNF217 at ERalpha target genes. Future studies will investigate whether ZNF217 expression contributes to aberrant ERalpha regulatory events in ER+ breast cancer and hormone resistance Overall design: Differential RNA-seq profiling from triplicate biological replicates of MCF7 cells treated with scrambled siRNA or siZNF217.
Global analysis of ZNF217 chromatin occupancy in the breast cancer cell genome reveals an association with ERalpha.
No sample metadata fields
View SampleshEPI-NCSC are neural crest derived multipotent somatic stem cells that persist in hair follicle stem cell niche, termed the bulge, and persist into adulthood (Clewes O et al, 2011). The purpose of this project was to generate two gene expression profiles, (1) of ex vivo expanded hEPI-NCSC (XP) and (2) of cells, whihc after expansion were grown in a culture medium (NP1), which was empirically designed to pre-differentiate the multipotent stem cells into neural stemcell like cells.
Differentiation of human epidermal neural crest stem cells (hEPI-NCSC) into virtually homogenous populations of dopaminergic neurons.
Sex, Specimen part
View SamplesThe objective of this study was to characterise a small panel of differentially expressed genes in the muscle that could be utilised to authenticate animals raised on pasture versus animals raised indoors on a concentrate based diet.
The application of transcriptomic data in the authentication of beef derived from contrasting production systems.
Specimen part
View SamplesTo facilitate the search for genetic modifiers that modulate ARPKD disease progression and severity, we sought to generate a congenic rat model that carries the PCK Pkhd1 mutation but is resistant to the development of ARPKD. We transferred the Pkhd1 mutation from the PCK rat onto the genetic background of the FHH (Fawn-Hooded Hypertensive) rat. This newly developed strain, called FHH.Pkhd1, showed significant amelioration of renal disease, and delayed onset of biliary abnormalities. To initiate the exploration for genes and pathways that modulate susceptibility to renal cystogenesis, we investigated transcriptional changes in kidneys from PCK, SD, FHH and FHH.Pkhd1 rats by microarray analysis.
Role of genetic modifiers in an orthologous rat model of ARPKD.
Age, Specimen part
View SamplesA cell line was derived from a mammary carcinoma in the transgenic FVB/N-Tg(MMTV-ErbB2)NDL2-5Mul mouse. The line, referred to as “NDL(UCD)” is adapted to standard cell culture and can be transplanted into syngeneic FVB/N mice. The line maintains a stable phenotype over multiple in vitro passages and rounds of in vivo transplantation. The cell line exhibits high expression of ErbB2 and ErbB3 and signaling molecules downstream from ErbB2. The line was previously shown to be reactive to anti-immune checkpoint therapy with responses conducive to immunotherapy studies. Here, using both histology/immunophenotyping and gene expression/microarray analysis, we show that the syngeneic transplant tumors elicit an immune reaction in the adjacent stroma, with additional tumor infiltrating lymphocytes. We also show that this immune activating effect is greater in the syngeneic transplants than in the primary tumors arising in the native transgenic mouse. We further analyzed the PD-1 and PD-L-1 expression in the model and found PD-L1 expression in the tumors and in vitro. In conclusion these data document the validity and utility of this cell line for in vivo preclinical immunotherapy trials. Overall design: Flash frozen NDL(UCD) cell line tumor transplants were sampled and whole-transcriptome analysis was performed by next-generation sequencing (NGS)-based RNA-Sequencing. This series includes three biological replicates of the same cell line grown in three different (but same strain) mouse.
A Syngeneic ErbB2 Mammary Cancer Model for Preclinical Immunotherapy Trials.
Sex, Specimen part, Cell line, Subject
View SamplesCMPF is elevated in diabetes and is associated with impaired insulin secretion. We used microarrays to determine the effect of CMPF on gene expression in isolated islets.
The furan fatty acid metabolite CMPF is elevated in diabetes and induces β cell dysfunction.
Sex, Age, Specimen part, Treatment
View Samples