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GSE99898
Homo sapiens
38 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Thirty-eight tumors from 17 patients treated with BRAF inhibitor (n=12) or combination BRAF/MEK inhibitors (n=5) with known PD-L1 expression were analyzed. RNA expression arrays were performed on all pre-treatment (PRE, n=17), early during treatment (EDT, n=8) and progression (PROG, n=13) biopsies. HLA-A/HLA-DPB1 expression was assessed by immunohistochemistry (IHC). Gene set enrichment analysis (GSEA) of PRE, EDT and PROG melanomas revealed that transcriptome signatures indicative of immune cell activation were strongly positively correlated with PD-L1 staining. In contrast, MAPK signaling and canonical Wnt/--catenin activity were negatively associated with PD-L1 melanoma expression. The expression of PD-L1 and immune activation signatures did not simply reflect the degree or type of immune cell infiltration, and was not sufficient for tumor response to MAPK inhibition.
Publication Title
PD-L1 Expression and Immune Escape in Melanoma Resistance to MAPK Inhibitors.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 33 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Cutaneous, acral and mucosal subtypes of melanoma were evaluated by whole-genome sequencing, revealing genes affected by novel recurrent mutations to the promoter (TERT, DPH3, OXNAD1, RPL13A, RALY, RPL18A, AP2A1), 5-UTR (HNRNPUL1, CCDC77, PES1), and 3-UTR (DYNAP, CHIT1, FUT9, CCDC141, CDH9, PTPRT) regions. TERT promoter mutations had the highest frequency of any mutation, but neither they nor ATRX mutations, associated with the alternative telomere lengthening mechanism, were correlated with greater telomere length. Genomic landscapes largely reflected ultraviolet radiation mutagenesis in cutaneous melanoma and provided novel insights into melanoma pathogenesis. In contrast, acral and mucosal melanomas exhibited predominantly structural changes, and mutation signatures of unknown aetiology not previously identified in melanoma. The majority of melanomas had potentially actionable mutations, most of which were in components of the mitogen-activated protein kinase and phosphoinositol kinase pathways.
Publication Title
Whole-genome landscapes of major melanoma subtypes.
Sample Metadata Fields
No sample metadata fields
View Samples- Oryza sativa
- 12 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
Magnaporthe oryzae causes rice blast, the most devastating foliar fungal disease of cultivated rice. During disease development the fungus simultaneously maintains both biotrophic and necrotrophic growth corresponding to a hemi-biotrophic life style. The ability of M. oryzae to also colonize roots and subsequently develop blast symptoms on aerial tissue has been recognized. The fungal root infection strategy and the respective host responses are currently unknown. Global temporal expression analysis suggested a purely biotrophic infection process reflected by the rapid induction of defense response-associated genes at the early stage of root invasion and subsequent repression coinciding with the onset of intracellular fungal growth. The same group of down-regulated defense genes was increasingly induced upon leaf infection by M. oryzae where symptom development occurs shortly post tissue penetration. Our molecular analysis therefore demonstrates the existence of fundamentally different tissue-specific fungal infection strategies and provides the basis for enhancing our understanding of the pathogen life style.
Publication Title
Tissue-adapted invasion strategies of the rice blast fungus Magnaporthe oryzae.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 4 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Drosophila S2 cells were treated with Heat-shock protein 90 (Hsp90) inhibitor radicicol for 15min, 30min and 1h. Poly(A) RNA was isolated and sequenced. Overall design: Kinetics of transcriptional response to Hsp90 inhibition
Publication Title
Hsp90 globally targets paused RNA polymerase to regulate gene expression in response to environmental stimuli.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Homo sapiens
- 48 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
G protein alpha q and 11 are mutated in 80% of uveal melanoma. We observed that treatment with the BRD4 inhibitor JQ1 resulted in different phenotypic responses in G-protein mutant uveal melanoma cell lines and wild type uveal melanoma cell lines.
Publication Title
BRD4-targeted therapy induces Myc-independent cytotoxicity in Gnaq/11-mutatant uveal melanoma cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Neural precursor cells (NPCs) are multipotent cells that can generate neurons, astrocytes, and oligodendrocytes in the mammalian central nervous system. Although Zbtb20 was expressed in NPCs, its functions in neural development are not fully understood. We performed microarray analysis to examine changes in gene expression between control and Zbtb20-overexpressed NPCs.
Publication Title
Zbtb20 promotes astrocytogenesis during neocortical development.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HiSeq 2000, Illumina Genome Analyzer IIx
Description
The Photo-Activatable Ribonucleoside-enhanced CrossLinking and ImmunoPrecipitation (PAR-CLIP) method was recently developed for global identification of RNAs interacting with proteins. The strength of this versatile method results from induction of specific T to C transitions at sites of interaction. However, current analytical tools do not distinguish between non-experimentally and experimentally induced transitions. Furthermore, geometric properties at potential binding sites are not taken into account. To surmount these shortcomings, we developed a two-step algorithm consisting of a non-parametric two-component mixture model and a wavelet-based peak calling procedure. Our algorithm can reduce the number of false positives up to 24% thereby identifying high confidence interaction sites. We successfully employed this approach in conjunction with a modified PAR-CLIP protocol to study the functional role of nuclear MOV10, a putative RNA helicase interacting with Argonaute2 and Polycomb. Our method, available as the R package wavClusteR, is generally applicable to any substitution-based inference problem in genomics. Overall design: The data comprises one MOV10 PAR-CLIP data file and one nuclear RNA-seq file
Publication Title
Mixture models and wavelet transforms reveal high confidence RNA-protein interaction sites in MOV10 PAR-CLIP data.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Three cell types, intermediolateral column motoneurons, medial motoneurons, and lateral motoneurons were isolated from a single adult spinal cord using laser capture microscopy. Four hundred captures were collected for each cell type. For a given cell type, RNA was extracted from the 400 captures using an Arcturus picopure kit. RNA was split in half and two targets were produced using a double amplification protocol. Each target was hybridized to Affymetrix chips and signals were normalized with R-pack. Inverse logs are provided. Five animals were used in these experiments, and all three cell types were collected from each animal. Thus, for each cell type, there are five biological replicates, and for each biological replicate there are two technical replicates. In all thirty chips were analyzed. Techinical replicates are indicated as Set 1 and Set 2. Animal numbers are indicated by Pair1 through Pair 5.
Publication Title
Divergence between motoneurons: gene expression profiling provides a molecular characterization of functionally discrete somatic and autonomic motoneurons.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Elevated levels of androgen receptor (AR) in prostate cancer confer resistance to current antiandrogens and play a causal role in disease progression due to persistent target gene activation. Through pharmacologic and genetic approaches, we show that half of all direct AR target genes, including TMPRSS2, the primary driver of ETS fusion transcripts in 70 percent of human prostate cancers, require histone deacetylase (HDAC) activity for transcriptional activation by AR. Surprisingly, the HDAC3-NCoR complex, which typically functions to repress gene expression by nuclear receptors, is required for AR target gene activation. Prostate cancer cells treated with HDAC inhibitors have reduced AR protein levels, but we show that the mechanism of blockade of AR activity is through failure to assemble a coactivator/RNA polymerase II complex after AR binds to the enhancers of target genes. Failed complex assembly is associated with a phase shift in the cyclical wave of AR recruitment that typically occurs in response to ligand treatment. HDAC inhibitors retain the ability to block AR activity in hormone refractory prostate cancer models and therefore merit clinical investigation in this setting. HDAC-regulated AR target genes defined here can serve as biomarkers to ensure sufficient levels of HDAC inhibition.
Publication Title
Histone deacetylases are required for androgen receptor function in hormone-sensitive and castrate-resistant prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Elevated levels of androgen receptor (AR) in prostate cancer confer resistance to current antiandrogens and play a causal role in disease progression due to persistent target gene activation. Through pharmacologic and genetic approaches, we show that half of all direct AR target genes, including TMPRSS2, the primary driver of ETS fusion transcripts in 70 percent of human prostate cancers, require histone deacetylase (HDAC) activity for transcriptional activation by AR. Surprisingly, the HDAC3-NCoR complex, which typically functions to repress gene expression by nuclear receptors, is required for AR target gene activation. Prostate cancer cells treated with HDAC inhibitors have reduced AR protein levels, but we show that the mechanism of blockade of AR activity is through failure to assemble a coactivator/RNA polymerase II complex after AR binds to the enhancers of target genes. Failed complex assembly is associated with a phase shift in the cyclical wave of AR recruitment that typically occurs in response to ligand treatment. HDAC inhibitors retain the ability to block AR activity in hormone refractory prostate cancer models and therefore merit clinical investigation in this setting. HDAC-regulated AR target genes defined here can serve as biomarkers to ensure sufficient levels of HDAC inhibition.
Publication Title
Histone deacetylases are required for androgen receptor function in hormone-sensitive and castrate-resistant prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples