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GSE63882
Homo sapiens
40 Downloadable Samples
Illumina HumanWG-6 v3.0 expression beadchip
Description
INTRODUCTION: CDKN2A (p16) inactivation is common in lung cancer and occurs via homozygous deletions, methylation of promoter region, or point mutations. Although p16 promoter methylation has been linked to KRAS mutation and smoking, the associations between p16 inactivation mechanisms and other common genetic mutations and smoking status are still controversial or unknown. METHODS: We determined all three p16 inactivation mechanisms with the use of multiple methodologies for genomic status, methylation, RNA, and protein expression, and correlated them with EGFR, KRAS, STK11 mutations and smoking status in 40 cell lines and 45 tumor samples of primary non-small-cell lung carcinoma. We also performed meta-analyses to investigate the impact of smoke exposure on p16 inactivation. RESULTS: p16 inactivation was the major mechanism of RB pathway perturbation in non-small-cell lung carcinoma, with homozygous deletion being the most frequent method, followed by methylation and the rarer point mutations. Inactivating mechanisms were tightly correlated with loss of mRNA and protein expression. p16 inactivation occurred at comparable frequencies regardless of mutational status of EGFR, KRAS, and STK11, however, the major inactivation mechanism of p16 varied. p16 methylation was linked to KRAS mutation but was mutually exclusive with EGFR mutation. Cell lines and tumor samples demonstrated similar results. Our meta-analyses confirmed a modest positive association between p16 promoter methylation and smoking. CONCLUSION: Our results confirm that all the inactivation mechanisms are truly associated with loss of gene product and identify specific associations between p16 inactivation mechanisms and other genetic changes and smoking status.
Publication Title
Molecular portraits of epithelial, mesenchymal, and hybrid States in lung adenocarcinoma and their relevance to survival.
Sample Metadata Fields
Sex, Age, Race
View Samples- Bos taurus
- 36 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
BACKGROUND:
Publication Title
Milk yield responses to changes in milking frequency during early lactation are associated with coordinated and persistent changes in mammary gene expression.
Sample Metadata Fields
Specimen part, Time
View Samples- Bos taurus
- 14 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Milking dairy cows four times daily (4X) instead of twice daily (2X) during early lactation stimulates an increase in milk yield that partly persists through late lactation; however, the mechanisms behind this response are unknown. We hypothesized that the acute mammary response to regular milkings would be transient and would involve different genes from those that may be specifically regulated in response to 4X. Nine multiparous cows were assigned at parturition to unilateral frequent milking (UFM; 2X of the left udder half, 4X of the right udder half). Mammary biopsies were obtained from both rear quarters at 5 days in milk (DIM), immediately after 4X glands had been milked (Experiment 1; n = 4 cows), or 2.5 h after both udder halves had last been milked (Experiment 2; n = 5 cows). Affymetrix GeneChip Bovine Genome Arrays were used to measure gene expression. Eight hundred and fifty five genes were differentially expressed in mammary tissue between 2X vs. 4X glands of cows in experiment 1 (FDR 0.05), whereas none were differentially expressed in experiment 2 using the same criterion. We conclude that there is an acute transcriptional response to milk removal, but 4X milking did not elicit differential expression of unique genes. Therefore, there does not appear to be a sustained transcriptional response to 4X milking on day 5 of lactation. Using a differential expression plot of data from both experiments, as well as qRT-PCR, we identified at least two genes that may be responsive to both milk removal and to 4X milking. Therefore, the milk yield response to 4X milking may be mediated by genes that are acutely regulated by removal of milk from the mammary gland.
Publication Title
Acute milk yield response to frequent milking during early lactation is mediated by genes transiently regulated by milk removal.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Bos taurus
- 14 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Cows exposed to short day photoperiod (SD, 8L:16D) during the 60-day non-lactating period prior to parturition produce more milk in their subsequent lactation compared to cows exposed to long day photoperiod (LD,16L:8D). Although this response is well-established in dairy cows, the underlying mechanisms are not understood. We hypothesized that differential gene expression in cows exposed to SD or LD photoperiods during the dry period could be used to identify the functional basis for the subsequent increase in milk production during lactation. Pregnant, multiparous cows were maintained on a SD or LD photoperiod for 60-days prior to parturition. Mammary biopsies were obtained on days -24 and -9 relative to parturition and Affymetrix GeneChip Bovine Genome Arrays were used to quantify gene expression. Sixty-four genes were differentially expressed (p 0.05 and fold-change |1.5|) between SD and LD treatments. Many of these genes were associated with cell growth and proliferation, or immune function. Ingenuity Pathway Analysis predicted upstream regulators to include TNF, TGF1, interferon and several interleukins. In addition, expression of 125 genes was significantly different between day -24 and day -9; those genes were associated with milk component metabolism and immune function. The interaction of photoperiod and time affected 32 genes associated with insulin-like growth factor (IGF-I) signaling. Genes differentially expressed in response to photoperiod were associated with mammary development and immune function consistent with the enhancement of milk yield in the ensuing lactation. Our results provide insight into the mechanisms by which photoperiod affects the mammary gland and subsequently lactation.
Publication Title
Responses of the mammary transcriptome of dairy cows to altered photoperiod during late gestation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Keloids are scars that extend beyond original wounds and are resistant to treatment. In order to improve understanding of the molecular basis of keloid scarring, we have assessed the genomic profiles of keloid fibroblasts and keratinocytes.
Publication Title
Keloid-derived keratinocytes exhibit an abnormal gene expression profile consistent with a distinct causal role in keloid pathology.
Sample Metadata Fields
Sex, Age, Specimen part, Race
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Using EWS-FLI and its parental transcription factor, FLI1, we created a unique experimental system to address questions regarding the genomic mechanisms by which chimeric transcription factors cause cancer. We found that in tumor cells, EWS-FLI targets regions of the genome distinct from FLI1, despite identical DNA-binding domains. In primary endothelial cells, however, EWS-FLI and FLI1 demonstrate similar targeting. To understand this mistargeting, we examined chromatin organization. Regions targeted by EWS-FLI are normally repressed and nucleosomal in primary endothelial cells. In tumor cells, however, bound regions are nucleosome-depleted and harbor the chromatin signature of enhancers. We next demonstrated that through chimerism, EWS-FLI acquired the ability to alter chromatin. Expression of EWS-FLI results in nucleosome depletion at targeted sites, whereas silencing of EWS-FLI in tumor cells restored nucleosome occupancy. Thus, the EWS-FLI chimera acquired chromatin-altering activity, leading to mistargeting, chromatin disruption, and ultimately transcriptional dysregulation.
Publication Title
Tumor-specific retargeting of an oncogenic transcription factor chimera results in dysregulation of chromatin and transcription.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The goal of the experiment: To characterize the dynamic gene expression profile of engineered human skin in vitro and after grafting, and compare with expression profile of uninjured human skin.
Publication Title
Engineered human skin substitutes undergo large-scale genomic reprogramming and normal skin-like maturation after transplantation to athymic mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
In two disparate models, we show that rapid revaccination following sublethal gamma radiation exposure rescues memory CD8+ T cell Responses.
Publication Title
Rescue of CD8+ T cell vaccine memory following sublethal γ irradiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
Targeted disruption of NRAS was performed in a stable 381T ERMS cell line harboring tamoxifen inducible CRISPR/Cas9 gRNA against NRAS Overall design: RNA sequencing was performed using RNA extracted from uninduced control 381T ERMS cells as well as tamoxifen (TAM)-induced ERMS cells with NRAS CRISPR/Cas9-mediated knockout. Each in 3 biological replicates.
Publication Title
Oncolytic Virus-Mediated RAS Targeting in Rhabdomyosarcoma.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 112 Downloadable Samples
- NextSeq 550
Description
Predicting the impact of cis-regulatory sequence on gene expression is a foundational challenge for biology. We combine polysome profiling of hundreds of thousands of randomized 5' UTRs with deep learning to build a predictive model that relates human 5' UTR sequence to translation. Together with a genetic algorithm, we use the model to engineer new 5? UTRs that accurately target specified levels of ribosome loading, providing the ability to tune sequences for optimal protein expression. We show that the same approach can be extended to chemically modified RNA, an important feature for applications in mRNA therapeutics and synthetic biology. We test 35,000 truncated human 5' UTRs and 3,577 naturally-occurring variants and show that the model accurately predicts ribosome loading of these sequences. Finally, we provide evidence of 47 SNVs associated with human diseases that cause a significant change in ribosome loading and thus a plausible molecular basis for disease. Overall design: Polysom profiling and sequencing was performed using a library of 300,000 randomized 5' UTR 50-mers with eGFP used as the CDS. Three RNA chemistries were tested: unmodified, pseudouridine, and 1-methylpseudouridine. These were performed in duplicate (6 samples total). A designed library that includes human 5' UTRs, SNVs, and sequences engineered with a genetic algorithm was used with the eGFP CDS (no duplicate). A second randomized library used mCherry as the CDS, also performed in duplicate.
Publication Title
Human 5' UTR design and variant effect prediction from a massively parallel translation assay.
Sample Metadata Fields
Specimen part, Subject
View Samples