Mutant nucleophosmin and cooperating pathways drive leukemia initiation and progression in mice
Ontology highlight
ABSTRACT:
Global profiling was done using Illumina mouse-6 expression beadchip version 2. Data were quantile normalised and analysed using the bioconductor (http://www.bioconductor.org/), lumi (http://www.bioconductor.org/packages/2.0/bioc/html/lumi.html ) and limma packages, then p-value adjusted for multiple testing.
ORGANISM(S): Mus musculus
SUBMITTER: George Vassiliou
PROVIDER: E-MEXP-3113 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Genome organization influences transcriptional regulation by facilitating interactions between gene promoters and distal regulatory elements. To analyse distal promoter contacts we used Capture Hi-C (CHi-C) to enrich for promoter-interactions in HiC libraries from mouse ESC and E14.5 fetal liver. Please note additional files included. These files were created using the following protocol: Significantly interacting regions were called using the GOTHiC BioConductor package (http://www.bioconductor.org/packages/devel/bioc/html/GOTHiC.html) as described in (Mifsud et al.).<br>Update on December 2015: the original additional file E-MTAB-2414.additional.1.zip contained an earlier iteration of processed data and not the one that was used for the published paper. The file now contains the correct list of interactions.
2015-02-01 | E-MTAB-2414 | biostudies-arrayexpress
Project description:The purpose of our study is to construct rat aortic smooth cell line A7r5-specific interactome by aggregating publically available microarray samples, and provided a global view of biological process and identified transcription factors that regulate the transcriptomic changes. We collected 30 samples of A7r5 cell line microarray from 2 prior studies and our own study data, GSE87439. We performed normalization for Affymetrix microarray platform using SCAN.UPC R package (Release 3.9, PMID: 22959562, https://www.bioconductor.org/packages/release/bioc/html/SCAN.UPC.html). After normallizatin, we performed batch effect adjusting because datasets came from different laboratoriesand, and combined the datasets . The matrix data we deposited in GEO has normalized log2 signal intensity for 14,004 genes which are common across datasets. The genes were mapped to Rattus norvegicus Entrez Gene IDs. A7r5-specific interactome was assembled by Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe, PMID: 16723010). Then, we used Master Regulator Analysis-Fisher’s Extact Test (MRA-FET, PMID: 20531406) to infer transcription factors which control a gene signature changes by the effect of SCE and SchB on the TGFβ1-treated A7r5 cells (PMID: 29423034). We discovered Junb, Srebf2, Foxk2, and Irf9 as a master regulator to modulate the gene signatures on the TGFβ1-treated A7r5 cells. Our findings will provide biological insights into the pharmaceutical effect of SCE and SchB in A7r5 cells.
2020-02-13 | GSE134932 | GEO
Project description:Experiment type: Expression profiling by microarray and RNA-seq data, Third-party re-analysis The purpose of our study is to construct breast cancer cell line BT20-specific interactome by aggregating publically available microarray or RNA-seq samples, and identify novel transcriptional regulators that control breast cancer progression. We collected 101 samples of BT20 cell line microarray or RNA-seq from 12 prior studies and our own study data, GSE120919. We performed normalization for Affymetrix microarray platform and Illumina HiSeq and NovaSeq platform datasets. For the normalization, we used SCAN.UPC R package (ver.2.24.0, PMID: 22959562, https://www.bioconductor.org/packages/release/bioc/html/SCAN.UPC.html) on Affymetrix microarray platform datasets. We use Rsubread R package (ver.1.30.5, PMID: 23558742, http://bioconductor.org/packages/Rsubread/), TPM log2 values on Illumina HiSeq and NovaSeq platform datasets. And then, we performed batch effect adjusting to combine the datasets which came from different laboratories. The matrix data we deposited in GEO has normalized log2 signal intensity for 12,360 genes, and the genes were mapped to human Entrez Gene IDs that overlapped across 13 datasets (a total number of 101 samples). BT20-specific interactome was assembled by Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe, PMID: 16723010). Then, we used Master Regulator Analysis-Fisher?s Extact Test (MRA-FET, PMID: 20531406) to infer transcription factors which control a gene signature dysregulated by a fusion gene in BT20 cell line (please refer to GSE120919). We discovered SNAI2 as a master regulator candidate to modulate the gene signature in the fusion gene expressing BT20. Our findings will provide biological insights into the role of the fusion gene in breast cancer.
2020-03-28 | GSE123917 | GEO
Project description:The goal of this study was to identify genes in C2C12 myoblasts whose expression was altered by overexpression of Smad3. Four total samples were analyzed. Two biological replicates were prepared from C2C12 cells infected with retroviral vector encoding wildtype Smad3 and exposed for 24 hours to 100 pM TGF-β. Two biological replicates were prepared from C2C12 cells infected with a control retrovirus that did not encode Smad3 (empty vector, EV) and exposed for 24 hours to 100pM TGF-β. To identify genes with altered expression between empty vector controls and cells overexpressing wild-type Smad3, we first pre-processed the four arrays using robust multiarray averaging as implemented in the R software package ‘xps’, version 1.10.2 (http://www.bioconductor.org/packages/release/bioc/html/xps.html). This preprocessing corrects for background noise and array effects, and aggregates probe data to 28,836 genes. Duplicates were averaged on the base-2 logarithm scale, and then we took differences between the averages to obtain logarithm-scale fold changes. Genes were selected which showed at least a two-fold change (raw scale) between wild-type and empty vector expressing cells. Due to the limited sample size, we did not apply any statistical tests to estimate false-discovery rate. This resulted in 79 genes that were at least two-fold higher in the wild-type Smad3-expressing C2C12 cells compared to empty vector cells and 25 genes that were at least two-fold lower in the wild-type Smad3-expressing cells than the in the empty vector cells.
2011-10-20 | E-GEOD-30459 | biostudies-arrayexpress
Project description:Assembly of eukaryotic ribosomes begins in the nucleolus, a compartmentalized membraneless organelle. Although the two ribosomal subunits, 40S and 60S, assemble independently, it remains unknown if these particles are physically sorted as they assemble and how they partition from the central chromatin compartment into the outer nucleolar regions, where maturation occurs. In this study, we show that nucleophosmin specifically mediates the assembly of nascent 60S subunits and that this specificity is determined by its chromatin localization at the rDNA sites encoding for 60S subunit rRNA. Nucleophosmin dissociates from chromatin to bind nascent 60S subunits, causing their partitioning away from chromatin and from nascent 40S subunits through liquid-liquid phase separation. This directs translocation of nascent 60S subunits towards the nucleophosmin-rich granular component, where biogenesis continues. Notably, this compartmentalization increases the efficiency of 60S subunit assembly, specifically the incorporation of the 60S domain III. Our data reveal that the chromatin localization of nucleophosmin determines its specificity in sorting and coordinates the movement of ribosomal subunits into specialized assembly compartments.
2023-03-01 | GSE156203 | GEO
Project description:Orientia tsutsugamushi, an obligate intracellular bacterium, is the causative agent of scrub typhus. As O. tsutsugamushi is detected in circulating monocytes during acute phase of scrub typhus, we wondered if this organism was able to infect monocytes. We showed here that O. tsutsugamushi replicated in monocytes from healthy donors. Using human whole genome microarrays, we found that O. tsutsugamushi the expression of genes in which up-regulated and down-modulated genes were equally distributed. , the expression of type I interferon, interferon-stimulated genes and M1-associated genes was significantly up-regulated. Second, O. tsutsugamushi the expression of apoptosis-related genes and induced cell death in monocytes. Live organisms were indispensable to type I interferon response and apoptosis and enhanced the expression of M1 cytokines. These findings were related to the transcriptional changes found in mononuclear cells from patients with scrub typhus. Hence, a microarray study revealed the up-regulation of 613 genes and the down-modulation of 517 genes. Importantly, IFN-related genes were specifically enriched and some features of M1 polarization were observed in patients, as found in O. tsutsugamushi-stimulated cells. Our results provide a comprehensive understanding of scrub typhus pathogenesis in which IFN-mediated activation of monocytes appears as critical. Monocytes (1.5 x 105 per assay) were incubated with or without 3 x 105 O. tsutsugamushi organisms in RPMI 1640 containing 10% FBS, 20 mM HEPES and 2 mM L-glutamine (Invitrogen) for 2 hours. The raw data, from the Agilent feature extraction software, were preprocessed with background subtraction and quantile normalization. This pretreatment was performed by using a bioconductor limma package, called Agi4x44PreProcess (http://www.bioconductor.org/packages/2.3/bioc/html/ Agi4x44PreProcess.html)
2010-09-21 | E-GEOD-24247 | biostudies-arrayexpress
Project description:Purpose: To identify regulatory proteins that are potential drivers of a coordinated breast cancer metastasis gene expression signatures. Methods: Knockdown of target genes in breast cancer cell lines was achieved using scramble and/or gene-specific siRNA (ON-TARGET SMARTpool, Thermo Scientific) and Lipofectamine RNAiMAX. 48h post transfection, total RNA was isolated from cell lines using the RNeasy Plus mini prep kit (Qiagen). Nucleic acid quality was determined with the Agilent 2100 Bioanalyzer. RNA Sequencing was also performed at the New York Genome Center (Manhattan, NY, USA) using a HiSeq 2500 Ultra-High-Throughput Sequencing System (Illumina, San Diego, CA, USA). Results: Raw reads in the fastq format were aligned to Human Genome HG19 using the RNA-seq STAR aligner version 2.4.0d (http://www.ncbi.nlm.nih.gov/pubmed/23104886, http://www.ncbi.nlm.nih.gov/pubmed/26334920) as recommended by user manual downloaded along with the software. STAR aligner was chosen for mapping accuracy and speed (http://www.nature.com/nmeth/journal/v10/n12/full/nmeth.2722.html). Mapped reads for each sample were counted for each gene in annotation files in GTF format (gencode.v19.annotation.gtf available for download from GENECODE website (http://www.gencodegenes.org/releases/19.html)) using the FeatureCounts read summarization program (http://www.ncbi.nlm.nih.gov/pubmed/?term=24227677) following the user guide (http://bioinf.wehi.edu.au/subread-package/SubreadUsersGuide.pdf). Individual count files were merged to generate the raw-counts matrix by an in-house R script, normalized to account for differences in library size and the variance was stabilized by fitting the dispersion to a negative-binomial distribution as implemented in the DESeq R package (http://bioconductor.org/packages/release/bioc/html/DESeq.html)(Anders and Huber, 2010). Conclusions: Our data suggest that targeting keystone proteins in the breast cancer metastasis transcriptome can effectively collapse transcriptional hierarchies necessary for metastasis formation, thus representing a formidable cancer intervention strategy.
2017-04-01 | GSE79586 | GEO
Project description:Multilineage dysplasia (MLD) has no impact on biological, clinico-pathological and prognostic features of AML with mutated nucleophosmin (NPM1) NPM1-mutated AML is a provisional entity in the WHO-2008 classification of myeloid neoplasms. The significance of concomitant multilineage dysplasia (MLD) in NPM1-mutated AML is unclear. Thus, in the WHO-2008 classification, NPM1-mutated AML with MLD is classified as AML with myelodysplasia(MD)-related changes. We evaluated the MLD impact in 378 NPM1-mutated AML patients. MLD was found in about 25% cases. Except for a lower WBC and FLT3-ITD incidence in MLD+ group, no significant differences were observed in age, sex, cytogenetics and FLT3-TKD between NPM1-mutated AML with and without MLD. Notably, NPM1-mutated AML with/without MLD showed overlapping immunophenotype (CD34-negativity) and GEP (CD34 downregulation and HOX genes upregulation). Moreover, OS and EFS did not differ among NPM1-mutated AML patients, independently of whether they carried or not MLD, the NPM1-mutated/FLT3-ITD negative cases showing the better prognosis. Lack of MLD impact on survival was confirmed by multivariate analysis that highlighted FLT3-ITD as the most significant prognostic parameter in NPM1-mutated AML. Our findings indicate that NPM1 mutations rather than MLD dictate the distinctive features of NPM1-mutated AML. Thus, irrespective of MLD, NPM1-mutated AML should be considered as one disease entity clearly distinct from AML with MD-related changes. These findings have important diagnostic and prognostic implications in AML. All bone marrow samples were obtained from untreated patients at the time of diagnosis. Cells used for microarray analysis were collected from the purified fraction of mononuclear cells after Ficoll density centrifugation. 48 samples
2010-07-30 | E-GEOD-18018 | biostudies-arrayexpress
Project description:Nucleophosmin sustains WNT-driven cell proliferation and tumor initiation in vivo
| PRJNA1051495 | ENA
Project description:Circular RNAs of the nucleophosmin (NPM1) gene in acute myeloid leukemia
| PRJNA408239 | ENA