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GSE60621
Homo sapiens
6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Anagrelide is a cytoreductive agent used to lower platelet counts in essential thrombocythemia. Although the drug is known to selectively inhibit megakaryopoiesis, the molecular mechanism accounting for this activity has not been elucidated.
Publication Title
The gene expression signature of anagrelide provides an insight into its mechanism of action and uncovers new regulators of megakaryopoiesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
BACKGROUND: Common variants in the TCF4 gene are among the most robustly supported genetic risk factors for schizophrenia. Rare TCF4 deletions and loss-of-function point mutations cause Pitt-Hopkins syndrome, a developmental disorder associated with severe intellectual disability.
Publication Title
Knockdown of the schizophrenia susceptibility gene <i>TCF4</i> alters gene expression and proliferation of progenitor cells from the developing human neocortex.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Bos taurus
- 47 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Background: Mycobacterium avium subspecies paratuberculosis (MPTb) is the causative agent of Johnes disease, an intestinal disease of ruminants with major economic consequences. MPTb bacilli are phagocytosed by host macrophages upon exposure where they persist, resulting in lengthy subclinical phases of infection that can lead to immunopathology and disease dissemination. Consequently, analysis of the macrophage transcriptome in response to MPTb infection can provide valuable insights into the molecular mechanisms that underlie Johnes disease. Here, we investigate pan-genomic gene expression in bovine monocyte-derived macrophages (MDM) purified from seven age-matched non-related females, in response to in vitro infection with MPTb (multiplicity of infection 2:1) at intervals of 2 hours, 6 hours and 24 hours post-infection.
Publication Title
Pan-genomic analysis of bovine monocyte-derived macrophage gene expression in response to in vitro infection with Mycobacterium avium subspecies paratuberculosis.
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples- Bos taurus
- 39 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Mycobacterium bovis is an intracellular pathogen that causes tuberculosis in cattle. Following infection, the pathogen resides and persists inside host macrophages by subverting host immune responses via a diverse range of mechanisms. Here, a high-density bovine microarray platform was used to examine the bovine monocyte-derived macrophage transcriptome response to M. bovis infection relative to infection with the attenuated vaccine strain, M. bovis Bacille CalmetteGurin. Differentially expressed genes were identified (adjusted P-value 0.01) and interaction networks generated across an infection time course of 2, 6 and 24 h. The largest number of biological interactions was observed in the 24 h network, which exhibited small-worldscale-free network properties. The 24 h network featured a small number of key hub and bottleneck gene nodes, including IKBKE, MYC, NFKB1 and EGR1 that differentiated the macrophage response to virulent and attenuated M. bovis strains, possibly via the modulation of host cell death mechanisms. These hub and bottleneck genes represent possible targets for immunomodulation of host macrophages by virulent mycobacterial species that enable their survival within a hostile environment.
Publication Title
Key Hub and Bottleneck Genes Differentiate the Macrophage Response to Virulent and Attenuated Mycobacterium bovis.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Time
View Samples- Bos taurus
- 16 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Background: Mycobacterium bovis is the causative agent of bovine tuberculosis (BTB), a pathological infection with significant economic impact. Recent studies have highlighted the role of functional genomics to better understand the molecular mechanisms governing the host immune response to M. bovis infection. Furthermore, these studies may enable the identification of novel transcriptional markers of BTB that can augment current diagnostic tests and surveillance programmes. In the present study, we have analysed the transcriptome of peripheral blood leukocytes (PBL) from eight M. bovis-infected and eight control non-infected age-matched and sex-matched Holstein-Friesian cattle using the Affymetrix GeneChip Bovine Genome Array with features representing more than 23,000 gene transcripts and over 19,000 gene probe sets.
Publication Title
Genome-wide transcriptional profiling of peripheral blood leukocytes from cattle infected with Mycobacterium bovis reveals suppression of host immune genes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Bos taurus
- 77 Downloadable Samples
Illumina HiSeq 2000
Description
Mycobacterium bovis, the agent of bovine tuberculosis, causes an estimated $3 billion annual losses to global agriculture due, in part, to the limitations of current diagnostics. Development of next-generation diagnostics requires a greater understanding of the interaction between the pathogen and the bovine host. Therefore, to explore the early response of the alveolar macrophage to infection, we report the first application of RNA-sequencing to define, in exquisite detail, the transcriptomes of M. bovis-infected and non-infected alveolar macrophages from ten calves at 2, 6, 24 and 48?hours post-infection. Differentially expressed sense genes were detected at these time points that revealed enrichment of innate immune signalling functions, and transcriptional suppression of host defence mechanisms (e.g., lysosome maturation). We also detected differentially expressed natural antisense transcripts, which may play a role in subverting innate immune mechanisms following infection. Furthermore, we report differential expression of novel bovine genes, some of which have immune-related functions based on orthology with human proteins. This is the first in-depth transcriptomics investigation of the alveolar macrophage response to the early stages of M. bovis infection and reveals complex patterns of gene expression and regulation that underlie the immunomodulatory mechanisms used by M. bovis to evade host defence mechanisms. Overall design: Whole-transcriptome analysis of M. bovis- and non-infected alveolar macrophages from ten calves (n = 10) at 2, 6, 24 and 48 hours (h) post-infection using RNA-sequencing (RNA-seq).
Publication Title
RNA sequencing provides exquisite insight into the manipulation of the alveolar macrophage by tubercle bacilli.
Sample Metadata Fields
Sex, Specimen part, Subject, Time
View Samples- Bos taurus
- 48 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Background: Mycobacterium bovis, the causative agent of bovine tuberculosis, is a major cause of mortality in global cattle populations. Macrophages are among the first cells types to encounter M. bovis following exposure and the response elicited by these cells is pivotal in determining the outcome of infection. Here, a functional genomics approach was undertaken to investigate global gene expression profiles in bovine monocyte-derived macrophages (MDM) purified from seven age-matched non-related females, in response to in vitro challenge with M. bovis (multiplicity of infection 2:1). Total cellular RNA was extracted from non-challenged control and M. bovis-challenged MDM for all animals at intervals of 2 hours, 6 hours and 24 hours post-challenge and prepared for global gene expression analysis using the Affymetrix GeneChip Bovine Genome Array.
Publication Title
Global gene expression and systems biology analysis of bovine monocyte-derived macrophages in response to in vitro challenge with Mycobacterium bovis.
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples- Homo sapiens
- 32 Downloadable Samples
- NextSeq 500
Description
We fine-mapped DNA methylation in neuronal nuclei (NeuN+) isolated by flow cytometry from post-mortem frontal cortex of the brain of individuals diagnosed with schizophrenia, bipolar disorder, and controls (n=29, 26, and 28 individuals). Overall design: Brain tissue samples (n=34 human samples, 17 case and 17 control) were lysed using QIAzol Lysis Reagent (Qiagen) and homogenized with a TissueLyser (Qiagen). Total RNA from each sample was isolated using the RNeasy Plus Universal Mini kit (Qiagen) according to manufacturer's instructions and included an enzymatic DNase (Qiagen) digestion step. RNA quality was measured on a 2100 Bioanalyzer (Agilent) and quantity was determined with a Nanodrop 2000 spectrophotometer (Thermo Fisher Scientific). Only RNA samples with a RIN quality score >7 proceeded to RNA-seq library preparation (RIN between 7.1 to 9.4 for all samples). Libraries were prepared by the Van Andel Genomics Core from 300 ng of total RNA using the KAPA RNA HyperPrep Kit with RiboseErase (v1.16) (Kapa Biosystems). RNA was sheared to 300-400 bp. Prior to PCR amplification, cDNA fragments were ligated to Bio Scientific NEXTflex Adapters (Bioo Scientific). Quality and quantity of the finished libraries were assessed using a combination of Agilent DNA High Sensitivity chip (Agilent Technologies, Inc.), QuantiFluor® dsDNA System (Promega Corp.), and Kapa Illumina Library Quantification qPCR assays (Kapa Biosystems). Individually indexed libraries were pooled, and 75 bp paired-end sequencing was performed on an Illumina NextSeq 500 sequencer, with all libraries run across 3 flowcells. Base calling was done by Illumina NextSeq Control Software (NCS) v2.0 and output of NCS was demultiplexed and converted to FastQ format with Illumina Bcl2fastq v1.9.0. Trimgalore (v0.11.5) was used for adapter removal prior to genome alignment. STAR33 (v2.3.5a) index was generated using Ensemble GRCh38 p10 primary assembly genome and the Gencode v26 primary assembly annotation. Read alignment was performed using a STAR two-pass mode. Gene counts matrix was imported into R (3.4.1) and low expressed genes (counts per million (CPM) < 1 in all samples) were removed prior to differential expression in EdgeR. Gene counts were normalized using the trimmed mean of M-values, fitted in a generalized linear model and differentially tested using a likelihood ratio test. The generalized linear model contained covariates age, sex, post mortem interval and neuronal cell composition. Cell-type compositions for each sample was accessed using CIBERSORT34 on normalized sample counts against cell-type specific markers, identifying the proportion of neurons in each samples. Benjamini Hochberg correction was used to adjust for multiple testing.
Publication Title
Differential methylation of enhancer at IGF2 is associated with abnormal dopamine synthesis in major psychosis.
Sample Metadata Fields
Sex, Age, Race, Subject
View Samples- Homo sapiens
- 200 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In order to gain insight into the molecular pathogenesis of the myelodysplastic syndromes (MDS), we performed global gene expression profiling and pathway analysis on the hematopoietic stem cells (HSC) of 183 MDS patients as compared with the HSC of 17 healthy controls. The most significantly deregulated pathways in MDS include interferon signaling, thrombopoietin signaling and the Wnt pathway. Among the most significantly deregulated gene pathways in early MDS are immunodeficiency, apoptosis and chemokine signaling, whereas advanced MDS is characterized by deregulation of DNA damage response and checkpoint pathways. We have identified distinct gene expression profiles and deregulated gene pathways in patients with del(5q), trisomy 8 or 7/del(7q). Patients with trisomy 8 are characterized by deregulation of pathways involved in the immune response, patients with 7/del(7q) by pathways involved in cell survival, whilst patients with del(5q) show deregulation of integrin signaling and cell cycle regulation pathways. This is the first study to determine deregulated gene pathways and ontology groups in the HSC of a large group of MDS patients. The deregulated pathways identified are likely to be critical to the MDS HSC phenotype and give new insights into the molecular pathogenesis of this disorder thereby providing new targets for therapeutic intervention.
Publication Title
Deregulated gene expression pathways in myelodysplastic syndrome hematopoietic stem cells.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 63 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In order to gain insight into the poorly understood pathophysiology of the myelodysplastic syndromes (MDS), we have determined the gene expression profiles of the CD34+ cells of 55 MDS patients using the Affymetrix GeneChip U133 Plus2.0 platform
Publication Title
Gene expression profiles of CD34+ cells in myelodysplastic syndromes: involvement of interferon-stimulated genes and correlation to FAB subtype and karyotype.
Sample Metadata Fields
No sample metadata fields
View Samples