This dataset contains gene expression data from the NRC series (Neuroblastoma Research Consortium) for a total of 283 primary neuroblastoma tumors. All tumor samples are fully annotated including patient age at diagnosis, overall and progresison free survival and MYCN amplification status, enabling subgroup analysis, survival analysis and gene expression network analysis.
Cross-Cohort Analysis Identifies a TEAD4-MYCN Positive Feedback Loop as the Core Regulatory Element of High-Risk Neuroblastoma.
No sample metadata fields
View SamplesNetwork-based analysis of neuroblastoma samples from two large cohorts identified master regulator proteins controlling the transcriptional state of three high-risk molecular subtypes. In particular, a TEAD4-MYCN positive feedback loop emerged as the core regulatory motif of a small protein module presiding over implementation and stability of the subtype associated with MYCN amplification. Specifically, MYCN transcriptionally activates TEAD4, which in turn activates MYCN both transcriptionally and post-translationally. The resulting MYCN-TEAD4 positive feedback loop plays a critical role in maintaining aberrant activity of a 10-protein regulatory module that causally regulates the transcriptional state of this subtype. Consistently, loss of TEAD4 activity induces core module activity collapse and abrogates neuroblastoma cell viability in vitro and in vivo, thus suggesting novel therapeutic strategies for this important childhood cancer. Overall design: Study of the transcriptional control by TEAD4 and MYCN positive feedback loop using RNA-seq profiles of TEAD4, WWTR1 and MYCN shRNA knockdowns in neuroblastoma BE2 cells. ChIP-Seq analysis using TEAD4 antibody in BE2 cells.
Cross-Cohort Analysis Identifies a TEAD4-MYCN Positive Feedback Loop as the Core Regulatory Element of High-Risk Neuroblastoma.
No sample metadata fields
View SamplesThe study entails novel bio-marker discovery of Tumor Aggressive Grade signature (TAGs) genes and their role in recurrence free survival of breast cancer (BC) patients. Current BC dataset was used for co-expression analysis of TAGs genes and their role in BC progression. Additionally, recent findings have suggested an importance of structural organization of sense-antisense gene pairs (SAGPs) for transcription, post-transcriptional and post-translational events and their associations with cancer and disease. We studied SAGPs in which both gene partners are protein encoding genes (coding-coding SAGPs), their role in human BC development and demonstrated their potential for BC stratification and prognosis. Based on gene expression and correlation analyses we identified the robust set of breast cancer-relevant SAGPs (BCR-SAGPs). We isolated and characterized the sense-antisense gene signature (SAGS) and evaluated its prognostic potential in various gene expression datasets comprising 1161 BC patients. The methods used included the Cox proportional survival analysis, statistical analysis of clinicopathologic parameters and differential gene expression. The SAGS was effective in identification of BC patients with the most aggressive disease. Independently, we validated the SAGS using 58 RNA samples of breast cancer tumors purchased from OriGene Technologies (Rockville, MD).
Sense-antisense gene-pairs in breast cancer and associated pathological pathways.
Age, Disease, Disease stage
View SamplesRetinal ganglion cells (RGCs) and retinal pigment epithelium (RPE) cells are two retinal cell types that are affected by the most prevalent retinal diseases leading to irreversible blindness, such as glaucoma affecting the former and age-related macular degeneration affecting the latter. One of the most promising approaches for the therapy of these diseases is via the autologous transplantation of RGC or RPE cells derived from the induced pluripotent stem cells (iPSCs). This emphasizes the importance of detailed characterization and understanding of the mechanisms of differentiation of iPSCs into retinal lineages on the genome-wide scale. Such information can be used to identify novel crucial regulators of differentiation, optimisation of differentiation protocols to make them more efficient and safe, identification of novel specific biomarker signatures of differentiated cells. In this study, we performed the genome-wide transcriptome analysis of terminally differentiated RGC and RPE lineages, as well as intermediate retinal progenitor cells (RPCs) of optic vesicles (OVs) derived from the human induced pluripotent stem cells (iPSCs). In our analysis we specifically focused on the classes of transcripts that encode regulators of gene expression, such as transcription factors, epigenetic factors, and components of signaling pathways.
Expression profiling of cell-intrinsic regulators in the process of differentiation of human iPSCs into retinal lineages.
Specimen part
View SamplesLebers hereditary optic neuropathy (LHON) is a maternally inherited mitochondrial disease caused by homoplasmic mutations in complex I subunit genes, and is characterized by incomplete penetrance. The mechanism of low penetrance of complex I mutation is still largely unclear today. In this study, we created the patient-specific induced pluripotent stem cells (iPSCs) from MT-ND4 mutated LHON affected patient, asymptomatic mutation carrier and control, and differentiated them into retinal ganglion cells (RGCs) for pathogenesis survey. We observed the following phenotypic features in the LHON-specific RGCs as compared to the control: 1) enhanced mitochondrial biogenesis in affected and carriers; 2) compensatory increased mitochondrial complex I activity in carrier, but not in affected patient; 3) reduced spare respiratory activity in affected and carrier. Microarray profiling of LHON-specific RGCs revealed abundant overexpression of genes encoding components of cell cycle regulation machinery as compared to the control.
Bioactivity and gene expression profiles of hiPSC-generated retinal ganglion cells in MT-ND4 mutated Leber's hereditary optic neuropathy.
Specimen part, Disease
View SamplesAbf1 and Rap1 are General Regulatory Factors that contribute to transcriptional activation of a large number of genes, as well as to replication, silencing, and telomere structure in yeast. In spite of their widespread roles in transcription, the scope of their functional targets genome-wide has not been previously determined. We have used microarrays to examine the contribution of these essential GRFs to transcription genome-wide, by using ts mutants that dissociate from their binding sites at 37 C. We combined this data with published ChIP-chip studies and motif analysis to identify probable direct targets for Abf1 and Rap1. We also identified a substantial number of genes likely to bind Rap1 or Abf1, but not affected by loss of GRF binding. Interestingly, the results strongly suggest that Rap1 can contribute to gene activation from farther upstream than can Abf1. Also, consistent with previous work, more genes that bind Abf1 are unaffected by loss of binding than those that bind Rap1. Finally, we showed for several such genes that the Abf1 C-terminal region, which contains the putative activation domain, is not needed to confer this peculiar "memory effect" that allows continued transcription after loss of Abf1 binding.
Genome-wide analysis of transcriptional dependence and probable target sites for Abf1 and Rap1 in Saccharomyces cerevisiae.
No sample metadata fields
View SamplesExpression profile for undifferentiated F9 Embryonal Carcinoma cell line
Identification of active transcriptional regulatory modules by the functional assay of DNA from nucleosome-free regions.
No sample metadata fields
View SamplesThis study provides a framework describing how magnetic exposure is transduced from the most-plausible molecular-level biosensor (lipid membranes) to cell-level responses that include differentiation toward neural lineages. In addition, SMF provided a stimulus that uncovered new relationships that exist even in the absence of magnetic fields between gangliosides, the time dependent regulation of IL-6 signaling by these glycolipids, and the fate of embryonic cells.
Moderate strength (0.23-0.28 T) static magnetic fields (SMF) modulate signaling and differentiation in human embryonic cells.
No sample metadata fields
View SamplesThis study identified genomwide KCl inducible readthrough transcription. The project also includes a Cap-Seq experiment to identify transcriptional start sites, demonstrating that KCl does not activate downstream transcriptional start sites, but indeed does induce readthrough
Widespread Inducible Transcription Downstream of Human Genes.
No sample metadata fields
View SamplesThese cultures were grown to examine the differences in Agr-regulated virulence factor gene expression between wild-type S. aureus FRI1169 and a non-hemolytic variant isolated from a biofilm inoculated with FRI1169. The study is described more thoroughly in the paper "Generation of virulence factor variants in Staphylococcus aureus biofilms", Yarwood et al., J. Bacteriol. 2007.
Generation of virulence factor variants in Staphylococcus aureus biofilms.
No sample metadata fields
View Samples