RNA-seq comparing transcriptome of lymphoblastic cells from FAME patients and control individuals
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina HiSeq 4000
ORGANISM(S): Homo sapiens
SUBMITTER: Plassard Damien
PROVIDER: E-MTAB-8301 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:RNAseq was performed for 10 individuals: three affected individuals (CSDN14, CSDN15, CSDN16) and one healthy spouse (CSDN17) from Family 1, three affected individuals (CSDN11, CSDN12, CSDN13) from Family 5 and three healthy controls (CSDN18, CSDN19, CSDN20).
2019-09-16 | E-MTAB-8300 | biostudies-arrayexpress
Project description:Disrupted in schizophrenia 1 is a protein that is encoded by the DISC1 gene in humans. In coordination with a wide array of interacting partners, DISC1 has been shown to participate in the regulation of cell proliferation, differentiation, migration, neuronal axon and dendrite outgrowth, synapse formation and maturation, synaptic transmission, mitochondrial transport, fission and/or fusion, and cell-to-cell adhesion. Several studies have shown that unregulated expression or altered protein structure of DISC1 may predispose individuals to the development of schizophrenia, major depression, bipolar disorder, and other psychiatric conditions. The cellular functions that are disrupted by permutations in DISC1, which lead to the development of these disorders, have yet to be clearly defined and are the subject of current ongoing research.
2021-09-08 | PXD013391 | Pride
Project description:To reveal the risk CNVs of SZ in Chinese population, we recrited and enrolled 100 Chinese family trios with a schizophrenia affected children and both of their father and mother. SZ was diagnosed according to DSM-IV criteria by two independent psychiatrists. There gDNA we screen the genome-wide CNV using Agilent SurePrint G3 Human CGH Microarray Kit (1x1M) and Agilent sex-matched human DNA was used as reference. The CNV were called by ADM-2 statistical algorithms with a threshold of 6.0. We compared the burden of large rare CNVs and found that SZ probands carried more duplications and less deletions. Furtherly, we performed familial inheritance analysis of transmission disequilibrium and de novo CNV detection, validated several associated CNV loci with SZ susceptibility and also identify eight novel loci conferring risk of SZ
2021-10-01 | E-MTAB-8075 | biostudies-arrayexpress
Project description:Performed FloChIP for PU.1, RUNX3 and CEBPB to demonstrate feasibility of TF ChIP-seq on multiple factors.
2019-12-08 | E-MTAB-8553 | biostudies-arrayexpress
Project description:In this study, we have characterized a putative chloroplast ribosome assembly factor. To elucidate transcriptional responses caused by decreased chloroplast function, we have measured the transcriptome of wild-type and knock-down seedlings.
2018-08-16 | E-MTAB-6866 | biostudies-arrayexpress
Project description:Background: Eosinophilic esophagitis (EoE) is a chronic non-IgE-mediated allergic disease of the esophagus. An unbiased proteomics approach was performed to investigate pathophysiological changes in esophageal epithelium. Additionally, an RNAseq-based transcriptomic analysis in paired samples was also carried out. Methods: Total proteins were purified from esophageal endoscopic biopsies in a cohort of adult EoE patients (n = 25) and healthy esophagus controls (n = 10). Differentially accumulated (DA) proteins in EoE patients compared to control tissues were characterized to identify altered biological processes and signaling pathways. Results were also compared with a quantitative proteome dataset of the human esophageal mucosa. Next, results were contrasted with those obtained after RNAseq analysis in paired samples. Finally, we matched up protein expression with two EoE-specific mRNA panels (EDP and Eso-EoE panel). Results: A total of 1667 proteins were identified, of which 363 were DA in EoE. RNA sequencing in paired samples identified 1993 differentially expressed (DE) genes. Total RNA and protein levels positively correlated, especially in DE mRNA-proteins pairs. Pathway analysis of these proteins in EoE showed alterations in immune and inflammatory responses for the upregulated proteins, and in epithelial differentiation, cornification and keratinization in those downregulated. Interestingly, a set of DA proteins, including eosinophil-related and secreted proteins, were not detected at the mRNA level. Protein expression positively correlated with EDP and Eso-EoE, and corresponded with the most abundant proteins of the human esophageal proteome. Conclusions: We unraveled for the first time key proteomic features involved in EoE pathogenesis. An integrative analysis of transcriptomic and proteomic datasets provides a deeper insight than transcriptomic alone into understanding complex disease mechanisms.
2025-04-11 | PXD062507 | Pride
Project description:Myocyte enhancer factor 2B (MEF2B) is a transcription factor with somatic mutation hotspots at K4, Y69 and D83 in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). The recurrence of these mutations indicates that they may drive lymphoma development. However, inferring the mechanisms by which they may drive lymphoma development was complicated by our limited understanding of MEF2B’s normal functions. To expand our understanding of the cellular activities of wildtype (WT) and mutant MEF2B, I developed and addressed two hypotheses: (1) identifying genes regulated by WT MEF2B will allow identification of cellular phenotypes affected by MEF2B activity and (2) contrasting the DNA binding sites, effects on gene expression and effects on cellular phenotypes of mutant and WT MEF2B will help refine hypotheses about how MEF2B mutations may contribute to lymphoma development. To address these hypotheses, I first identified genome-wide WT MEF2B binding sites and transcriptome-wide gene expression changes mediated by WT MEF2B. Using these data I identified and validated novel MEF2B target genes. I found that target genes of MEF2B included the cancer genes MYC, TGFB1, CARD11, NDRG1, RHOB, BCL2 and JUN. Identification of target genes led to findings that WT MEF2B promotes expression of mesenchymal markers, promotes HEK293A cell migration, and inhibits DLBCL cell chemotaxis. I then investigated how K4E, Y69H and D83V mutations change MEF2B’s activity. I found that K4E, Y69H and D83V mutations decreased MEF2B DNA binding and decreased MEF2B’s capacity to promote gene expression in both HEK293A and DLBCL cells. These mutations also reduced MEF2B’s capacity to alter HEK293A and DLBCL cell movement. From these data, I hypothesize that MEF2B mutations may promote DLBCL and FL development by reducing expression of MEF2B target genes that would otherwise function to help confine germinal centre B-cells to germinal centres. Overall, my research demonstrates how observations from genome-scale data can be used to identify cellular effects of candidate driver mutations. Moreover, my work provides a unique resource for exploring the role of MEF2B in cell biology: I map for the first time the MEF2B ‘regulome’, demonstrating connections between a relatively understudied transcription factor and genes significant to oncogenesis. ChIP-seq was performed using a V5 antibody on cells expressing V5 tagged WT and mutant MEF2B. Two biological replicates were performed on WT, K4E, Y69H and D83V MEF2B-V5 cells.
2015-07-01 | E-GEOD-67450 | biostudies-arrayexpress
Project description:Myocyte enhancer factor 2B (MEF2B) is a transcription factor with somatic mutation hotspots at K4, Y69 and D83 in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). The recurrence of these mutations indicates that they may drive lymphoma development. However, inferring the mechanisms by which they may drive lymphoma development was complicated by our limited understanding of MEF2B’s normal functions. To expand our understanding of the cellular activities of wildtype (WT) and mutant MEF2B, I developed and addressed two hypotheses: (1) identifying genes regulated by WT MEF2B will allow identification of cellular phenotypes affected by MEF2B activity and (2) contrasting the DNA binding sites, effects on gene expression and effects on cellular phenotypes of mutant and WT MEF2B will help refine hypotheses about how MEF2B mutations may contribute to lymphoma development. To address these hypotheses, I first identified genome-wide WT MEF2B binding sites and transcriptome-wide gene expression changes mediated by WT MEF2B. Using these data I identified and validated novel MEF2B target genes. I found that target genes of MEF2B included the cancer genes MYC, TGFB1, CARD11, NDRG1, RHOB, BCL2 and JUN. Identification of target genes led to findings that WT MEF2B promotes expression of mesenchymal markers, promotes HEK293A cell migration, and inhibits DLBCL cell chemotaxis. I then investigated how K4E, Y69H and D83V mutations change MEF2B’s activity. I found that K4E, Y69H and D83V mutations decreased MEF2B DNA binding and decreased MEF2B’s capacity to promote gene expression in both HEK293A and DLBCL cells. These mutations also reduced MEF2B’s capacity to alter HEK293A and DLBCL cell movement. From these data, I hypothesize that MEF2B mutations may promote DLBCL and FL development by reducing expression of MEF2B target genes that would otherwise function to help confine germinal centre B-cells to germinal centres. Overall, my research demonstrates how observations from genome-scale data can be used to identify cellular effects of candidate driver mutations. Moreover, my work provides a unique resource for exploring the role of MEF2B in cell biology: I map for the first time the MEF2B ‘regulome’, demonstrating connections between a relatively understudied transcription factor and genes significant to oncogenesis. ChIP-seq was performed using H3K27ac and H3K4me3 antibodies on cells expressing V5 tagged WT MEF2B and on empty vector control cells. Two biological replicates were performed.
2015-07-01 | E-GEOD-67455 | biostudies-arrayexpress
Project description:Mitochondrial oxidative phosphorylation (OXPHOS) fuels cellular ATP demands. OXPHOS defects lead to severe human disorders with unexplained tissue specific pathologies. Mitochondrial gene expression is essential for OXPHOS biogenesis since core subunits of the complexes are mitochondrial-encoded. COX14 is required for translation of COX1, the central mitochondrial-encoded subunit of complex IV. Here we generated a COX14 mouse mutant corresponding to a patient with complex IV deficiency. COX14M19I mice display broad tissue-specific pathologies. A hallmark phenotype is severe liver inflammation linked to release of mitochondrial RNA into the cytosol sensed by RIG-1 pathway. We find that mitochondrial RNA release is triggered by increased reactive oxygen species production in the absence of complex IV. Additionally, we also generated a COA3Y72C mouse, affected in COX1 biogenesis, which displays a similar yet milder inflammatory phenotype. Our study provides mechanistic insight into how defective mitochondrial gene expression causes tissue-specific inflammation.
2024-07-25 | PXD041783 | Pride
Project description:We described a striking divergence between the phenotypes arising from acute (siDOCK6) and chronic (DOCK6 KO cells) depletion is highly suggestive of a suppression mechanism that buffers the prolonged absence of DOCK6. This mechanism is probably also active in AOS patients who harbor homozygous loss-of-function mutations in DOCK6 because the actin organization patterns in their fibroblasts resemble those of DOCK6 KO cells (Shaheen et al., 2011). To identify the factor(s) that compensate for the lack of DOCK6 activity, we compared mRNA profiles of fibroblasts isolated from an AOS patient who harbored a homozygous 4 base pair deletion in the DOCK6 gene (c.1362_1365delAACT, p.Thr455Serfs*24; RefSeq accession number: NM_020812.2) with two healthy controls (Shaheen et al., 2011)
2016-09-29 | E-MTAB-5067 | biostudies-arrayexpress