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SRP073186
Homo sapiens
53 Downloadable Samples
Illumina HiSeq 2500
Description
While long noncoding RNAs (lncRNAs) and mRNAs share similar biogenesis pathways, these two transcript classes differ in many regards. LncRNAs are less conserved, less abundant, and more tissue specific than mRNAs, implying that our understanding of lncRNA transcriptional regulation is incomplete. Here, we perform an in depth characterization of numerous factors contributing to this regulation. We find that lncRNA promoters contain fewer transcription factor binding sites than do those of mRNAs, with some notable exceptions. Surprisingly, we find that H3K9me3 –typically associated with transcriptional repression–is enriched at active lncRNA loci. However, the most discriminant differences between lncRNAs and mRNAs involve splicing: only half of lncRNAs are efficiently spliced, which can be partially attributed to defects in lncRNA splicing signals and diminished U2AF65 binding. These attributes are conserved between humans and mice. Finally, we find that certain transcriptional properties are enriched in known, functionally characterized lncRNAs, demonstrating that our multidimensional analysis might discern lncRNAs that are likely to be functional Overall design: Examination of RNA abundance in two cell lines (K562 and Hues9) and 5 time points after actinomycin D treatment. Three replicates per time point and cell type.
Publication Title
Chromatin environment, transcriptional regulation, and splicing distinguish lincRNAs and mRNAs.
Sample Metadata Fields
Cell line, Subject, Time
View Samples- Gallus gallus
- 12 Downloadable Samples
Affymetrix Chicken Genome Array (chicken)
Description
The microarray analysis was designed to test the effects of HES5.3 siRNAs, Atoh7 siRNAs and nt siRNAs on gene expression in embryonic chick retina.
Publication Title
A positive feedback loop between ATOH7 and a Notch effector regulates cell-cycle progression and neurogenesis in the retina.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
We attempted to identify alterations in gene expression that occur during the progression from normal breast to ductal carcinoma in situ (DCIS) with the aim to elucidate significant genes and pathways underlying the premalignant transformation. To determine the expression changes that are common to multiple DCIS models (MCF10.DCIS, SUM102 and SUM225) and normal mammary epithelial cells (MCF10A), we grew the cells in three dimensional overlay culture with reconstituted basement membrane and used the extracted RNA for 76 cycles of deep sequencing (mRNA-Seq) using Illumina Genome Analyzer GAIIx. Analysis of mRNA-Seq results showed 295 consistently differentially expressed transcripts in DCIS models as compared to MCF10A. These differentially expressed genes are associated with a number of signaling pathways such as integrin, fibroblast growth factor and TGFß signaling. Many differentially expressed transcripts in DCIS were found to be involved in cell-cell signaling, cell-cell adhesion and cell proliferation. We further investigated ALDH5A1 gene that encodes for the enzyme, aldehyde dehydrogenase 5A1, which is involved in glutamate metabolism. Further, inhibition of ALDH5A1 with different pharmacological drugs resulted in significant inhibition of cell growth and proliferation in the DCIS models. Overall design: Four cell lines examined: normal mammary epithelial cell line (one sample) and three ductal carcinoma in situ cell lines (three samples). Each sample has two duplicates
Publication Title
RNA-Seq of human breast ductal carcinoma in situ models reveals aldehyde dehydrogenase isoform 5A1 as a novel potential target.
Sample Metadata Fields
Disease, Cell line, Subject
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Anaplastic Large Cell Lymphomas (ALCL) represent a subset of lymphomas in which the Anaplastic Lymphoma Kinase (ALK) gene is frequently fused to the NPM gene. We previously demonstrated that the constitutive phosphorylation of ALK chimeric proteins is sufficient to induce cellular transformation in vitro and in vivo, and that ALK activity is strictly required for the survival of ALK positive ALCL cells. To elucidate the signaling pathways required for ALK-mediated transformation and tumor maintenance, we analyzed the transcriptomes of multiple ALK positive ALCL cell lines abrogating their ALK-mediated signaling by inducible ALK RNA interference (RNAi) or with potent and cell permeable ALK inhibitors. Transcripts derived from the gene expression profiling (GEP) analysis uncovered a reproducible signature, which included a novel group of ALK-regulated genes. Functional RNAi screening on a set of these ALK transcriptional targets revealed that the transcription factor C/EBPb and the anti-apoptotic protein BCL2A1 are absolutely necessary to induce cell transformation and/or to sustain the growth and survival of ALK positive ALCL cells. Thus, we proved that an experimentally controlled and functionally validated GEP analysis represents a powerful tool to identify novel pathogenetic networks and validate biologically suitable target genes for therapeutic interventions.
Publication Title
Functional validation of the anaplastic lymphoma kinase signature identifies CEBPB and BCL2A1 as critical target genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
In order to investigate the patterns of genetic lesions in a panel of 23 Human Multiple Myeloma Cell Lines (HMCLs), we made a genomic integrative analysis involving FISH and both gene expression and genome-wide profiling approaches. The expression profiles of the genes targeted by the main IGH translocations showed that the WHSC1/MMSET gene involved in t(4;14)(p16;q32) was expressed at different levels in all of the HMCLs, and that the expression of the MAF gene was not restricted to the HMCLs carrying t(14;16)(q32;q23). Supervised analyses identified a limited number of genes specifically associated with t(4;14) and involved in different biological processes. The signature related to MAF/MAFB expression included the known MAF target genes CCND2 and ITGB7, as well as genes controlling cell shape and cell adhesion. Genomewide DNA profiling allowed the identification of a gain on chromosome arm 1q in 88% of the analyzed cell lines, together with recurrent gains on 8q, 18q, 7q and 20q; the most frequent deletions affected 1p, 13q, 17p and 14q; and almost all of the cell lines presented LOH on chromosome 13. Two hundred and twenty-two genes were found to be simultaneously overexpressed and amplified in our panel, including the BCL2 locus at 18q21.33. Our data further support the evidence of the genomic complexity of multiple myeloma and reinforce the role of an integrated genomic approach in improving our understanding of the molecular pathogenesis of the disease.
Publication Title
Molecular characterization of human multiple myeloma cell lines by integrative genomics: insights into the biology of the disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- UNKNOWN
Description
Evaluation of two commercial microarray platforms (Amersham CodeLink UniSet Human 10K I BioArray and Affymetrix GeneChip HG-U133A). Both platforms have been tested on gene expression profiling of MDA-MB-231 human metastatic breast cancer cells, cultured for 48 h in the absence (control) or presence (treated) of 32 µM resveratrol.
Publication Title
Strategies for comparing gene expression profiles from different microarray platforms: application to a case-control experiment.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Cell line, Compound
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
To determine a gene/molecular fingerprint of multiple myeloma (MM) endothelial cells (MMECs), also identifying some of the vascular mechanisms that govern the malignant progression from quiescent monoclonal gammopathy of undetermined significance (MGUS). A comparative gene expression profiling (GEP) was carried out on patient-derived MMECs and MGUS endothelial cells (MGECs) using the Affymetrix U133A Arrays. Expression of selective vascular markers were also validated by RT-PCR and immunoblotting analysis in primary cultures of ECs isolated from total bone marrow (BM)-mononuclear cells. Twenty-two genes were found differently expressed in MMECs compared to MGECs (with 14 down-regulated and 8 up-regulated), thus proving that molecular differences were maintained in vitro. Specific pathways analysis revealed transcriptional and protein expression changes for key regulators of extracellular matrix formation and bone remodeling, cell-adhesion, chemotaxis, angiogenesis, resistance to apoptosis, and cell-cycle regulation. Specifically, we focused on six of these genes (DIRAS3, SERPINF1, SRPX, BNIP3, IER3 and SEPW1), which were not previously functionally correlated to the overangiogenic phenotype of MMECs and disease activity. These data identified distinct EC gene expression profiles and some vascular phenotypes that could influence the remodeling of the BM-microenvironment in patients with active MM. A better understanding of the linkage between genetic and epigenetic events in MM tumor/ECs may contribute to the molecular classification of the disease, thereby identifying selective targets of more effective anti-vessel/stroma therapeutic strategies.
Publication Title
Gene expression profiling of bone marrow endothelial cells in patients with multiple myeloma.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 863 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Identifying the Mechanism of Action (MoA) of drugs is critical for the development of new drugs, understanding their side effects, and drug repositioning. However, identifying drug MoA has been challenging and has been traditionally attempted only though large experimental setups with little success. While advances in computational power offers the opportunity to achieve this in-silico, methods to exploit existing computational resources are still in their infancy. To overcome this, we developed a novel method to identify Drug Mechanism of Action using Network Dysregulation (DeMAND).
Publication Title
Elucidating Compound Mechanism of Action by Network Perturbation Analysis.
Sample Metadata Fields
Cell line, Time
View Samples- Rattus norvegicus
- 33 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
The 6-hydroxydopamine (6OHDA) rat model of parkinsonism is among the first, and most commonly used, animal models of Parkinsons disease. It provides insight into the compensatory changes that occur in the brain after dopamine (DA) neuron degeneration. In order to better define the consequences of substantia nigra DA neuron loss on the neural and glial populations during and following nigrostriatal degeneration, tissue was collected and evaluated from the substantia nigra of 6OHDA or vehicle treated, or nave rats at 1, 2, 4, 6 & 16 weeks.
Publication Title
The longitudinal transcriptomic response of the substantia nigra to intrastriatal 6-hydroxydopamine reveals significant upregulation of regeneration-associated genes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Zea mays
- 19 Downloadable Samples
- Affymetrix Maize Genome Array (maize)
Description
Aluminum toxicity is one of the major limiting factors for many crops worldwide. The primary symptom of Al toxicity syndrome is the inhibition of root growth, leading to poor water and nutrient absorption. The causes of this inhibition are still elusive, with several biochemical pathways being affected and with a significant variation between species. Most of the work done so far to investigate the genes responsible for Al tolerance used hydroponic culture. Here we evaluated plant responses using soil as substrate, which is a condition closer to the field reality.
Publication Title
Transcriptional profile of maize roots under acid soil growth.
Sample Metadata Fields
Specimen part
View Samples