In order to understand the molecular mechanism behind Vulvar Intraepithelial Neoplasia (VIN), we have analyzed the gene expression profile of VIN lesions in comparison to controls.
HPV related VIN: highly proliferative and diminished responsiveness to extracellular signals.
Sex
View SamplesTranscriptomic analyses of the oxygen response of two glioma cell lines at 20% versus 0.3% O2, and 3% vs 0.3% O2 in the presence or absence of serum
Hypoxia-induced expression of VE-cadherin and filamin B in glioma cell cultures and pseudopalisade structures.
Specimen part, Cell line
View SamplesBackground: Strategies to improve long term renal allograft survival have been directed to recipient dependent mechanisms of renal allograft injury. In contrast, no such efforts have been made to optimize organ quality in the donor. In order to get insight into the deleterious gene pathways expressed at different time points during deceased kidney transplantation, transcriptomics was performed on kidney biopsies from a large cohort of deceased kidney transplants.
Hypoxia and Complement-and-Coagulation Pathways in the Deceased Organ Donor as the Major Target for Intervention to Improve Renal Allograft Outcome.
Specimen part
View SamplesWe sought to investigate the scope of cellular and molecular changes within a mouse's olfactory system as a function of its exposure to odors emitted from members of the opposite sex. To this end, we housed mice either separated from members of the opposite sex (sex-separated) or together with members of the opposite sex (sex-combined) until six months of age and then profiled transcript levels within the main olfactory epithelium (MOE), vomeronasal organ (VNO), and olfactory bulb (OB) of the mice via RNA-seq. For each tissue type, we then analyzed gene expression differences between sex-separated males and sex-separated females (SM v SF), sex-combined males and sex-combined females (CM v CF), sex-separated females and sex-combined females (SF v CF), and sex-separated males and sex-combined males (SM v CM). Within both the MOE and VNO, we observed significantly more numerous gene expression differences between males and females when mice were sex-separated as compared to sex-combined. Chemoreceptors were highly enriched among the genes differentially expressed between males and females in sex-separated conditions, and these expression differences were found to reflect differences in the abundance of the corresponding sensory neurons. Overall design: For each combination of tissue (MOE, VNO, OB), sex (F, M), and condition (sex-separated [S], sex-combined [C]), we generated three biological replicate samples of RNA, each of which contained equal quantities of RNA from two different mice. This resulted in a total of 36 samples.
Sex separation induces differences in the olfactory sensory receptor repertoires of male and female mice.
Sex, Age, Cell line, Subject
View SamplesA previously predictive CEBPA double mutant (CEBPAdm) signature was hampered by the recently reported CEBPA silenced AML cases that carry a similar gene expression profile (GEP). Two independent AML cohorts were used to train and evaluate the predictive value of the CEBPAdm signature in terms of sensitivity and specificity. A predictive signature was created, containing 25-probe sets by using a logistic regression model with Lasso regularization, which selects discriminative probe sets between the classes, CEBPAdm and all other AML cases, CEBPA wild type (CEBPAwt) and CEBPA single mutant (CEBPAsm). Subsequently, a classifier was trained on the entire HOVON-SAKK cohort based on a two-class approach; CEBPAdm versus all other cases (CEBPAwt and CEBPAsm). This trained classifier subsequently classified 16 candidate CEBPAdm cases in the AMLSG-cohort out of 154 AML cases. This approach showed perfect sensitivity and specificity (both 100%). In addition, we have performed a classification between CEBPAdm ,CEBPAsm, and CEBPAwt to infer if we were able to accurately classify CEBPAsm cases. We observed that all CEBPAsm cases were classified as CEBPAwt, thus CEBPAsm cases do not have a consistent gene expression pattern and are different from the CEBPAdm group.
Prognostic impact, concurrent genetic mutations, and gene expression features of AML with CEBPA mutations in a cohort of 1182 cytogenetically normal AML patients: further evidence for CEBPA double mutant AML as a distinctive disease entity.
No sample metadata fields
View SamplesPurpose: The purpose of this study is to identify functionally inter-connected group of miRNAs whose reduced expression promotes leukemia development in vivo. We searched for relevant target genes of these miRNAs that are upregulated in T-ALL relative to controls. Methods: In order to examine the global gene expression, we generated 9 T-ALL patients and 4 normal controls by deep sequencing using Illumina Hi-Seq sequencer. The sequence reads that passed quality filters were analyzed using Spliced Transcripts Alignment to a Reference aligner (STAR) followed by differential gene expression analysis using DESeq. Results: Using an optimized data analysis workflow, we mapped reads per sample to the human genome (build hg19) and identified transcripts in both patient and controls with STAR workflow. We applied a machine learning approach to eliminate targets with redundant miRNA-mediated control. This strategy finds a convergence on the Myb oncogene and less prominent effects on the Hpb1 transcription factor. The abundance of both genes is increased in T-ALL and each can promote T-ALL in vivo. Conclusion: Our study reveals a Myc regulated network of tumor suppressor miRNAs in T-ALL. We identified a small number of functionally validated tumor suppressor miRNAs. These miRNAs are repressed upon Myc activation and this links their expression directly to Myb a key oncogenic driver in T-ALL. Overall design: Examination of global gene expression in 9 T-ALL patients and 4 normal controls using total RNA sequencing. BaseMeanA in DESeq_results.xlsx is the control.
Characterization of a set of tumor suppressor microRNAs in T cell acute lymphoblastic leukemia.
No sample metadata fields
View SamplesmRNA profiles of thousands of human tumors are available, but methods to deduce oncogenic signaling networks from these data lag behind. It is especially challenging to identify main-regulatory routes, and to generalize conclusions obtained from experimental models. We designed the bioinformatic platform R2 in parallel with a wet-lab approach of neuroblastoma. Here we demonstrate how R2 facilitates an integrated analysis of our neuroblastoma data. Analysis of the MYCN pathway suggested important regulatory connections to the polyamine synthesis route, the Notch pathway and the BMP/TGF pathway. A network of genes emerged connecting major oncogenes in neuroblastoma. Genes in the network carried strong prognostic values and were essential for tumor cell survival.
Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes.
Specimen part
View SamplesWhether inflammatory macrophages can adopt features of the tissue resident niche and what mechanisms mediate phenotypic conversion remain unclear. In this study, we show by cell surface phenotyping, as well as by RNA-Seq transcriptional profiling and ATAC-Seq open chromatin regions profiling, that inflammatory monocyte can adopt a tissue resident phenotype, which is also accompanied by re-programming of the transcriptional profiles and remodeling of the open chromatin landscape. The conversion process is dependent on Vitamin A, suggesting that Vitamin A deficiency may lead to the failure to resolve inflammation, as inflammatory macrophages accumulate without adopting a tissue residency phenotype. Overall design: Monocyte-derived (N=3), tissue converted (N=3) and tissue resident (N=3) mouse peritoneal macrophages were FACS-sorted for RNASeq and ATACSeq.
Vitamin A mediates conversion of monocyte-derived macrophages into tissue-resident macrophages during alternative activation.
Specimen part, Subject
View SamplesNatural killer (NK) cells are innate lymphocytes that possess features of adaptive immunity, such as the ability to recognize specific antigen, among others. In MCMV infection, the engagement of a subset of NK cells expressing an activating receptor Ly49H with MCMV-derived glycoprotein m157 results in a clonal-like expansion and the generation of a small pool of long-lived memory cells with higher Ly49H expression than the naive Ly49H-expressing NK cell pool. In this study, we interrogate the transcriptional differences between NK cells that express high verus low levels of Ly49H early after infection. Overall design: RNASeq was performed on Ly49Hhi and Ly49Hlow NK cells harvested after 1.5 days post in vivo infection; 4 replicates per group and 50,000 cells per replicate.
Cytomegalovirus Infection Drives Avidity Selection of Natural Killer Cells.
Specimen part, Subject
View SamplesThe translational control of oncoprotein expression is implicated in many cancers. Here we report an eIF4A/DDX2 RNA helicase-dependent mechanism of translational control that contributes to oncogenesis and underlies the anticancer effects of Silvestrol and related compounds. For example, eIF4A promotes T-ALL development in vivo and is required for leukaemia maintenance. Accordingly, inhibition of eIF4A with Silvestrol has powerful therapeutic effects in vitro and in vivo. We use transcriptome-scale ribosome footprinting to identify the hallmarks of eIF4A-dependent transcripts. These include 5'UTR sequences such as the 12-mer guanine quartet (CGG)4 motif that can form RNA G-quadruplex structures. Notably, among the most eIF4A-dependent and Silvestrol-sensitive transcripts are a number of oncogenes, super-enhancer associated transcription factors, and epigenetic regulators. Hence, the 5'UTRs of selected cancer genes harbour a targetable requirement for the eIF4A RNA helicase. Overall design: Comparison of ribosome-protected RNA for drug treated and DMSO treated KOPT-K1 cell, two replicates of ribosome-protected RNA sequencing and three replicates of RNA-seq.
RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer.
No sample metadata fields
View Samples