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accession-icon GSE70617
Integrating high-dimensional transcriptomics and image analysis tools into early safety screening
  • organism-icon Homo sapiens
  • sample-icon 114 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U219 Array (hgu219), Affymetrix Human Gene 1.1 ST Array (hugene11st)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.

Sample Metadata Fields

Cell line, Treatment

View Samples
accession-icon GSE70611
Integrating high-dimensional transcriptomics and image analysis tools into early safety screening (I)
  • organism-icon Homo sapiens
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 1.1 ST Array (hugene11st)

Description

In this paper we demonstrated the potential to flag toxicity issues by utilizing data from exploratory experiments which are typically generated for target evaluation purposes during early drug discovery

Publication Title

Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.

Sample Metadata Fields

Cell line, Treatment

View Samples
accession-icon GSE70613
Integrating high-dimensional transcriptomics and image analysis tools into early safety screening (II)
  • organism-icon Homo sapiens
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U219 Array (hgu219), Affymetrix Human Gene 1.1 ST Array (hugene11st)

Description

In this paper we demonstrated the potential to flag toxicity issues by utilizing data from exploratory experiments which are typically generated for target evaluation purposes during early drug discovery

Publication Title

Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.

Sample Metadata Fields

Cell line, Treatment

View Samples
accession-icon GSE70614
Integrating high-dimensional transcriptomics and image analysis tools into early safety screening (III)
  • organism-icon Homo sapiens
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 1.1 ST Array (hugene11st)

Description

In this paper we demonstrated the potential to flag toxicity issues by utilizing data from exploratory experiments which are typically generated for target evaluation purposes during early drug discovery

Publication Title

Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.

Sample Metadata Fields

Cell line, Treatment

View Samples
accession-icon GSE45554
Resistant starch induces catabolic but suppresses immune and cell division pathways and changes the microbiome in proximal colon of male pigs
  • organism-icon Sus scrofa
  • sample-icon 20 Downloadable Samples
  • Technology Badge Icon Porcine Gene 1.0 ST Array (porgene10st)

Description

Consumption of resistant starch (RS) has been associated with various intestinal health benefits, but knowledge on its effects on global gene expression in the colon is limited. The main objective of the current study was to identify genes affected by RS in the proximal colon to infer which biologic pathways were modulated. Ten 17-wk-old male pigs, fitted with a cannula in the proximal colon for repeated collection of tissue biopsy samples and luminal content, were fed a digestible starch (DS) diet or a diet high in RS (34%) for 2 consecutive periods of 14 d in a crossover design. Analysis of the colonic transcriptome profiles revealed that, upon RS feeding, oxidative metabolic pathways, such as the tricarboxylic acid cycle and -oxidation, were induced, whereas many immune response pathways, including adaptive and innate immune system, as well as cell division were suppressed. The nuclear receptor peroxisome proliferator-activated receptor (PPARG) was identified as a potential key upstream regulator. RS significantly (P < 0.05) increased the relative abundance of several butyrate-producing microbial groups, including the butyrate producers Faecalibacterium prausnitzii and Megasphaera elsdenii, and reduced the abundance of potentially pathogenic members of the genus Leptospira and the phylum Proteobacteria. Concentrations in carotid plasma of the 3 main short-chain fatty acids acetate, propionate, and butyrate were significantly higher with RS consumption compared with DS consumption. Overall, this study provides novel insights on effects of RS in proximal colon and contributes to our understanding of a healthy diet.

Publication Title

Resistant starch induces catabolic but suppresses immune and cell division pathways and changes the microbiome in the proximal colon of male pigs.

Sample Metadata Fields

Sex, Age, Specimen part

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accession-icon SRP074892
HDAC inhibitor panobinostat engages host immune defenses to promote the tumoricidal effects of trastuzumab in HER2+ tumors
  • organism-icon Mus musculus
  • sample-icon 16 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

Characterisation of the tumor extrinsic (immune-mediated) mechanisms by which panobinostat and trastuzumab can collaboratively promote tumor-associated NK cell infiltration to eradicate trastuzumab-refractory HER2+ tumors Overall design: RNA sequencing was performed on established whole AU565(pv) HER2+ human breast tumors, harvested from SCID mice 2-days post treatment initiation with vehicle (PBS/D5W), panobinostat (15mg/kg/day), trastuzumab (10mg/kg day 1) or both drugs in combination. Each treatment group comprised of 4 mice.

Publication Title

HDAC Inhibitor Panobinostat Engages Host Innate Immune Defenses to Promote the Tumoricidal Effects of Trastuzumab in HER2<sup>+</sup> Tumors.

Sample Metadata Fields

Specimen part, Cell line, Subject

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accession-icon GSE10801
C. fulvum Avr2
  • organism-icon Arabidopsis thaliana
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)

Description

Heterologous expression of the fungal pathogen Cladosporium fulvum Avr2 in Arabidopsis plants.

Publication Title

The Cladosporium fulvum virulence protein Avr2 inhibits host proteases required for basal defense.

Sample Metadata Fields

No sample metadata fields

View Samples
accession-icon SRP090062
RNA-Sequencing analysis of BET inhibitor resistant cell lines
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

Targeting BET bromodomain proteins utilizing small molecules in an emerging anti-cancer strategy with clinical evaluation of at least six inhibitors now underway. While MYC downregulation was initially proposed as a key mechanistic property of BET inhibitors, recent evidence suggests that additional anti-tumor activities are important. Using the Eµ-Myc model of B-cell lymphoma we demonstrate that BET inhibition with JQ1 is a potent inducer of p53-independent apoptosis that occurs in the absence of effects on Myc gene expression. JQ1 skews the expression of pro-apoptotic (Bim) and anti-apoptotic (BCL-2/BCL-xL) BCL-2 family members to directly engage the mitochondrial apoptotic pathway. Consistent with this, Bim knockout or Bcl-2 overexpression inhibited apoptosis induction by JQ1. We identified lymphomas that were either intrinsically resistant to JQ1-mediated death or acquired resistance following in vivo exposure. Strikingly, in both instances BCL-2 was strongly upregulated and was concomitant with activation of RAS pathways. Eµ-Myc lymphomas engineered to express activated Nras upregulated BCL-2 and acquired a JQ1-resistance phenotype. These studies provide important information on mechanisms apoptosis induction and resistance to BET-inhibition, while providing further rationale for the translation of BET inhibitors in aggressive B-cell lymphomas. Overall design: RNA-Sequencing of JQ1 resistant and sensitive Eµ-Myc cell lines

Publication Title

BET Inhibition Induces Apoptosis in Aggressive B-Cell Lymphoma via Epigenetic Regulation of BCL-2 Family Members.

Sample Metadata Fields

Cell line, Subject

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accession-icon GSE100701
Lifelong calorie restriction and markers of colonic health in aging mice
  • organism-icon Mus musculus
  • sample-icon 41 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.1 ST Array (mogene11st)

Description

Diminishment of colonic health is associated with various age-related pathologies. Calorie restriction (CR) is an efficient strategy to increase healthy lifespan, although underlying mechanisms are not fully elucidated. Here we report the effects of lifelong CR on markers of colonic health in aging mice. We show that 30% energy reduction, as compared to a control (C) and moderate-fat (MF) diet, is associated with attenuated immune-related gene expression and lower levels of bile acids in the colon. Pronounced shifts in microbiota composition, together with lowered plasma levels of interleukin 6, in mice exposed to CR are in line with these findings. Furthermore, expression of genes involved in lipid metabolism was higher upon CR as compared to C and MF, pointing towards efficient regulation of energy metabolism. Switching from CR to an ad libitum MF diet at old age revealed remarkable phenotypic plasticity, although expression of a small subset of genes remained CR-associated. This research demonstrates that CR beneficially affects markers of colonic health in aging mice and as such may attenuate the progressive age-related decline in health.

Publication Title

Lifelong calorie restriction affects indicators of colonic health in aging C57Bl/6J mice.

Sample Metadata Fields

Sex, Specimen part

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accession-icon GSE113257
Integrative analysis of gut microbiota composition, host colonic gene expression and intraluminal metabolites in aging C57BL/6J mice
  • organism-icon Mus musculus
  • sample-icon 26 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.1 ST Array (mogene11st)

Description

Diminished colonic health is associated with various age-related pathologies. In this study, we applied an integrative approach to reveal potential interactions between determinants of colonic health in aging C57BL/6J mice. Analysis of gut microbiota composition revealed an enrichment of various potential pathobionts, including Desulfovibrio spp., and a decline of the health-promoting Akkermansia spp. and Lactobacillus spp. during aging. Intraluminal concentrations of various metabolites varied between ages and we found evidence for an increased gut permeability at higher age. Colonic gene expression analysis suggested that during the early phase of aging (between 6 and 12 months), expression of genes involved in epithelial-to-mesenchymal transition and (re)organization of the extracellular matrix were increased. Differential expression of these genes was strongly correlated with Bifidobacterium spp. During the later phase of aging (between 12 and 28 months), gene expression profiles pointed towards a diminished antimicrobial defense and were correlated with an uncultured Gastranaerophilales spp. This study demonstrates that aging is associated with pronounced changes in gut microbiota composition and colonic gene expression. Furthermore, the strong correlations between specific bacterial genera and host gene expression may imply that orchestrated interactions take place in the vicinity of the colonic wall and potentially mediate colonic health during aging.

Publication Title

Integrative analysis of gut microbiota composition, host colonic gene expression and intraluminal metabolites in aging C57BL/6J mice.

Sample Metadata Fields

Sex, Specimen part

View Samples
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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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