Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA105839 | ENA |
REPOSITORIES: ENA
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Project description:Background: The vast majority of human genes (.70%) are alternatively spliced. Although alternative pre-mRNA processing is modified in multiple tumors, alternative hyper-splicing signatures specific to particular tumor types are still lacking. Here, we report the use of Affymetrix Human Exon Arrays to spot hyper-splicing events characteristic of myasthenia gravis (MG)-thymoma, thymic tumors which develop in patients with MG and discriminate them from colon cancer changes. Methodology/Principal Findings: We combined GO term to parent threshold-based and threshold-independent ad-hoc functional statistics with in-depth analysis of key modified transcripts to highlight various exon-specific changes. These denote alternative splicing in MG-thymoma tumors compared to healthy human thymus and to in-house and Affymetrix datasets from colon cancer and healthy tissues. By using both global and specific, term-to-parent Gene Ontology (GO) statistical comparisons, our functional integrative ad-hoc method allowed the detection of disease-relevant splicing events. Conclusions/Significance: Hyper-spliced transcripts spanned several categories, including the tumorogenic ERBB4 tyrosine kinase receptor and the connective tissue growth factor CTGF, as well as the immune function-related histocompatability gene HLA-DRB1 and interleukin (IL)19, two muscle-specific collagens and one myosin heavy chain gene; intriguingly, a putative new exon was discovered in the MG-involved acetylcholinesterase ACHE gene. Corresponding changes in spliceosome composition were indicated by co-decreases in the splicing factors ASF/SF2 and SC35. Parallel tumor-associated changes occurred in colon cancer as well, but the majority of the apparent hyper-splicing events were particular to MGthymoma and could be validated by Fluorescent In-Situ Hybridization (FISH), Reverse Transcription–Polymerase Chain Reaction (RT-PCR) and mass spectrometry (MS) followed by peptide sequencing. Our findings demonstrate a particular alternative hyper-splicing signature for transcripts over-expressed in MG-thymoma, supporting the hypothesis that alternative hyper-splicing contributes to shaping the biological functions of these and other specialized tumors and opening new venues for the development of diagnosis and treatment approaches Keywords: Disease analysis, Tumor type comparison analysis
2008-07-03 | GSE11967 | GEO
Project description:This work provides the first evidence that Qk is a global regulator of splicing in vertebrates, defines a new splicing regulatory network in muscle, and suggests that overlapping splicing networks contribute to the complexity of changes in alternative splicing during differentiation. Alternative splicing contributes to muscle development and differentiation, but the complete set of muscle splicing factors and their combinatorial interactions are not known. Previously work identifies ACUAA (STAR motif) as an enriched sequence near muscle-specific alternative exons such as Capzb exon 9. We did mass spectrometry of proteins selected by wild type and mutant Capzb intron 9 RNA affinity chromatography, and identified Quaking (Qk), a protein known to regulate mRNA function through ACUAA motifs in 3' UTRs. We show that in myoblasts, Qk promotes inclusion of Capzb exon 9 in opposition to repression by PTB. Qk knockdown in myoblasts has little effect on transcript levels, but alters inclusion of 824 cassette exons whose adjacent intron sequences are enriched in ACUAA motifs. During differentiation to myotubes, Qk levels increase 2-3 fold, suggesting a mechanism for Qk-responsive exon regulation. We captured the PTB splicing regulatory network and intersected it with the Qk network, identifying overlap between the functions of Qk and PTB. Approximately 60% of exons whose inclusion is altered during myogenesis appear to be under control of one or both of these splicing factors in myoblasts. This series is the C2C12 Qk and PTB siRNA data. It is 12 arrays: 3 PTB siRNA arrays , 3 Qk siRNA arrays, and 6 mock siRNA arrays.
2013-06-05 | E-GEOD-40961 | biostudies-arrayexpress
Project description:We analyzed a role of histone deacetylases in alternative splicing regulation. Using human exon arrays we identified a list of 683 genes whose splicing changes after HDAC inhibition with sodium butyrate.
2011-02-03 | GSE17397 | GEO
Project description:We used Affymetrix exon arrays to identify potential changes in alternative splicing between mice affect with spinal muscular atropy (SMA) and their unaffected littermates. Keywords: disease state analysis
2008-05-16 | GSE10599 | GEO
Project description:This work provides the first evidence that Qk is a global regulator of splicing in vertebrates, defines a new splicing regulatory network in muscle, and suggests that overlapping splicing networks contribute to the complexity of changes in alternative splicing during differentiation. Alternative splicing contributes to muscle development and differentiation, but the complete set of muscle splicing factors and their combinatorial interactions are not known. Previously work identifies ACUAA (STAR motif) as an enriched sequence near muscle-specific alternative exons such as Capzb exon 9. We did mass spectrometry of proteins selected by wild type and mutant Capzb intron 9 RNA affinity chromatography, and identified Quaking (Qk), a protein known to regulate mRNA function through ACUAA motifs in 3' UTRs. We show that in myoblasts, Qk promotes inclusion of Capzb exon 9 in opposition to repression by PTB. Qk knockdown in myoblasts has little effect on transcript levels, but alters inclusion of 824 cassette exons whose adjacent intron sequences are enriched in ACUAA motifs. During differentiation to myotubes, Qk levels increase 2-3 fold, suggesting a mechanism for Qk-responsive exon regulation. We captured the PTB splicing regulatory network and intersected it with the Qk network, identifying overlap between the functions of Qk and PTB. Approximately 60% of exons whose inclusion is altered during myogenesis appear to be under control of one or both of these splicing factors in myoblasts. This series is the C2C12 differentiation data. It is 9 arrays, 3 timepoints, with 3 replicates. The time points are 0 hrs, 24 hrs, and 72hrs.
2013-06-05 | E-GEOD-40956 | biostudies-arrayexpress
Project description:The immune system relies on the plasticity of its components to produce appropriate responses to frequent environmental challenges. Dendritic cells (DCs) are critical initiators of innate immunity and orchestrate the later and more specific adaptive immunity. The generation of diversity in transcriptional programs is central for effective immune responses. Alternative splicing is widely considered a key generator of transcriptional and proteomic complexity, but its role has been rarely addressed systematically in immune cells. Here we used splicing-sensitive arrays to assess genome-wide gene- and exon-level expression profiles in human DCs in response to a bacterial challenge. We find widespread alternative splicing events and splicing factor transcriptional signatures induced by an E. coli challenge to human DCs. Alternative splicing acts in concert with transcriptional modulation, but these two mechanisms of gene regulation affect primarily distinct functional gene groups. Alternative splicing is likely to have an important role in DC immunobiology because it affects genes known to be involved in DC development, endocytosis, antigen presentation and cell cycle arrest
2012-11-28 | GSE42561 | GEO
Project description:The latest version of microarrays released by Affymetrix, the GeneChip Gene 1.0 ST Arrays (gene arrays), are designed in a similar fashion as exon arrays, which enables to identify differentially expressed exons, rather than only the expression level of whole transcripts. Here, we propose an extension, Gene Array Analyzer (GAA), to our previously published Exon Array Analyzer (EAA). GAA enables to analyse gene arrays on exon level and therefore supports to identify alternative splicing with gene arrays. To show the applicability of GAA, we used gene arrays to profile alternative splice events during the development of the heart. Further re-analysis of published gene arrays could show, that some of these splice events reoccur under pathological conditions. The web interface of GAA is user friendly, functional without set up and freely available at http://GAA.mpi-bn.mpg.de. Alternative splicing and gene expression analysis during development of the heart and cardiomyoyte differentiation.
2011-11-28 | E-GEOD-30429 | biostudies-arrayexpress
Project description:The latest version of microarrays released by Affymetrix, the GeneChip Gene 1.0 ST Arrays (gene arrays), are designed in a similar fashion as exon arrays, which enables to identify differentially expressed exons, rather than only the expression level of whole transcripts. Here, we propose an extension, Gene Array Analyzer (GAA), to our previously published Exon Array Analyzer (EAA). GAA enables to analyse gene arrays on exon level and therefore supports to identify alternative splicing with gene arrays. To show the applicability of GAA, we used gene arrays to profile alternative splice events during the development of the heart. Further re-analysis of published gene arrays could show, that some of these splice events reoccur under pathological conditions. The web interface of GAA is user friendly, functional without set up and freely available at http://GAA.mpi-bn.mpg.de. Alternative splicing and gene expression analysis during development of the heart and cardiomyoyte differentiation.
2011-11-28 | E-GEOD-32998 | biostudies-arrayexpress
Project description:AD is the leading cause of dementia in the elderly. However, disease etiology is still practically unknown. To gain insight into the molecular mechanisms underlying this disease we used the Affymetrix exon arrays to profile the alternative splicing landscape of human entorhinal cortex samples from AD patients and controls. We found a few hundred events of alternative spicing that characterize the AD entorhinal cortex and may have profound effect on the pathogenesis of this disease. Expression was analyzed using Affymetrix Human Exon 1 S.T arrays
2012-09-06 | GSE26972 | GEO
Project description:The latest version of microarrays released by Affymetrix, the GeneChip Gene 1.0 ST Arrays (gene arrays), are designed in a similar fashion as exon arrays, which enables to identify differentially expressed exons, rather than only the expression level of whole transcripts. Here, we propose an extension, Gene Array Analyzer (GAA), to our previously published Exon Array Analyzer (EAA). GAA enables to analyse gene arrays on exon level and therefore supports to identify alternative splicing with gene arrays. To show the applicability of GAA, we used gene arrays to profile alternative splice events during the development of the heart. Further re-analysis of published gene arrays could show, that some of these splice events reoccur under pathological conditions. The web interface of GAA is user friendly, functional without set up and freely available at http://GAA.mpi-bn.mpg.de.
2011-11-28 | GSE32998 | GEO