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SRP136794
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
- 19 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pediatric GIST commonly harbors a disabled succinate dehydrogenase complex (SDH), which yields tumors with highly conserved genomes but characteristic epigenomic signatures. Mysteriously, nearly half of such SDH-deficient GIST, including tumors from Carney Triad patients, lack identifiable mutations in SDH component genes and genes required for complex assembly (SDHA, SDHB, SDHC, SDHD, SDHAF, termed SDHx). Genomic sequencing coupled with DNA methylation and transcriptional profiling have exposed SDHC promoter-specific CpG island epimutation and concomitant gene silencing in the majority of SDHx-WT GIST.
Publication Title
Recurrent epimutation of SDHC in gastrointestinal stromal tumors.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human Natural Killer (NK) cells comprise two main subsets, CD56bright and CD56dim cells, that differ in function, phenotype and tissue localization. To further dissect the heterogeneity of CD56dim cells, we have performed transcriptome analysis and functional ex vivo characterization of human NK cell subsets according to the expression of markers related to differentiation, migration or competence. Here, we show for the first time that the ability to respond to cytokines or to activating receptors is mutually exclusive in almost all NK cells with the exception of CD56dim CD62L+ cells. Indeed, only these cells combine the ability to produce interferon (IFN)-gamma after cytokines and proliferate in vivo during viral infection with the capacity to kill and produce cytokines upon engagement of activating receptors. Therefore, CD56dim CD62L+ cells represent a unique subset of polyfunctional NK cells. Ex vivo analysis of their function, phenotype, telomere length, frequencies during ageing as well as transfer experiments of NK cell subsets into immunodeficient mice suggest that CD56dim CD62L+ cells represent an intermediate stage of NK cell maturation, which after restimulation can accomplish multiple tasks and further develop into terminally differentiated effectors.
Publication Title
CD62L expression identifies a unique subset of polyfunctional CD56dim NK cells.
Sample Metadata Fields
Specimen part
View Samples- Bos taurus
- 16 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
In both beef and dairy cattle, the majority of embryo loss occurs in the first 14-16 days following insemination. During this period, the embryo is completely dependent on its maternal uterine environment for development, growth and ultimately survival, therefore an optimum uterine environment is critical to embryo survival.
Publication Title
Endometrial gene expression in high- and low-fertility heifers in the late luteal phase of the estrous cycle and a comparison with midluteal gene expression.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Natural killer (NK) cells induce apoptosis in infected and transformed cells and produce immunoregulatory cytokines. At this, NK cells operate in inflammatory and tumor environments low in oxygen (hypoxic) and with immunosuppressive properties. In vitro studies of NK cells are, however, commonly performed in ambient air (normoxia).
Publication Title
Short Term Hypoxia Synergizes with Interleukin 15 Priming in Driving Glycolytic Gene Transcription and Supports Human Natural Killer Cell Activities.
Sample Metadata Fields
Specimen part, Disease stage
View Samples- 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- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
RORt+ innate lymphoid cells (ILC) are crucial players of innate immune responses and represent a major source of IL-22, which has an important role in mucosal homeostasis. The signals required by RORt+ ILC to express IL-22 and other cytokines, including TNF, have only partially been elucidated. Here we show that RORt+ ILC can directly sense the environment by the engagement of the activating receptor NKp44. NKp44 triggering in RORt+ ILC selectively activates a coordinated pro-inflammatory program, including TNF, while cytokine stimulation induces preferentially IL-22 expression. However, combined engagement of NKp44 and cytokine receptors results in a strong synergistic effect. These data support the concept that NKp44+ RORt+ ILC can be activated without cytokines and are able to switch between IL-22 or TNF production, depending on the triggering stimulus.
Publication Title
RORγt⁺ innate lymphoid cells acquire a proinflammatory program upon engagement of the activating receptor NKp44.
Sample Metadata Fields
Specimen part, Treatment
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