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GSE53418
Homo sapiens
31 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Epithelial ovarian cancer is a very heterogeneous disease and remains the most lethal gynaecological malignancy in the Western world. Rational therapeutic approaches need to account for interpatient and intratumoral heterogeneity in treatment design. Detailed characterization of in vitro models representing the different histological and molecular subtypes is therefore imperative. Strikingly, from ~100 available ovarian cancer cell lines the origin and which subtype they represent is largely unknown. We have extensively and uniformly characterized 39 ovarian cancer cell lines (with mRNA/microRNA expression, exon sequencing, dose response curves for clinically relevant therapeutics) and obtained all available information on the clinical features and tissue of origin of the original ovarian cancer to refine the putative histological subtypes. From 39 ovarian cell lines, 14 were assigned as high-grade serous, four serous-type, one low-grade serous and 20 non-serous type. Three morphological subtypes (21 Epithelial, 7 Round, 12 Spindle) were identified that showed distinct biological and molecular characteristics, including overexpression of cell movement and migration-associated genes for the Spindle subtype. Clinical validation showed a clear association of the spindle-like tumors with metastasis, advanced stage, suboptimal debulking and poor prognosis. In addition, the morphological subtypes associated with the molecular C1-6 subtypes identified by Tothill et al. [1], Spindle clustered with C1-stromal subtype, Round with C5-mesenchymal and Epithelial with C4 subtype. We provide a uniformly generated data resource for 39 ovarian cancer cell lines, the ovarian cancer cell line panel (OCCP). This should be the basis for selecting models to develop subtype specific treatment approaches, which is very much needed to prolong the survival of ovarian cancer patients.
Publication Title
Ovarian cancer cell line panel (OCCP): clinical importance of in vitro morphological subtypes.
Sample Metadata Fields
Cell line
View Samples- Drosophila melanogaster
- 2 Downloadable Samples
Illumina Genome Analyzer II
Description
Purpose: Validation of Drosophila A-to-I editing sites Methods: We collected heads of 5 day old male dAdar-/- mutant (y, Adar5G1, w)26 and wild type (w1118) flies. Poly(A)+ RNA was used to prepare RNA-seq libraries which were subsequently sequenced single-end by an Illumina GAII Results:We builded a framework to identify RNA editing events using RNA-seq data alone in Drosophila. To validate whether the identified A-to-G sites were bona fide A-to-I editing events, we performed RNA-seq for the D.melanogaster wild-type strain (w1118) and for the Adar5G1 null mutant that eliminates RNA editing. We found that our method achieved high accuracy; 98.2% of all A-to-G sites showed only adenosine in the Adar5G1 sample Conclusions: We anticipate that our method will be very effective in the future to identify RNA editing events in different species. Overall design: mRNA profiles of heads of 5 day old male dAdar-/- mutant (y, Adar5G1, w)26 and wild type (w1118) flies
Publication Title
Identifying RNA editing sites using RNA sequencing data alone.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: RNA editing by ADAR1 is essential for hematopoietic development. The goals of this study were firstly, to identify ADAR1-specific RNA-editing sites by indentifying A-to-I (G) mismatches in RNA-seq data compared to mm9 reference genome in wild type mice that were not edited or reduced in editing frequency in ADAR1E861A editing deficient mice. Secondly, to determine the transcriptional consequence of an absence of ADAR1-mediated A-to-I editing. Methods: Fetal liver mRNA profiles of embryonic day 12.5 wild-type (WT) and ADAR1 editing-deficient (ADAR1E861A) mice were generated by RNA sequencing, in triplicate (biological replicates), using Illumina HiSeq2000. The sequence reads that passed quality filters were analyzed at the transcript level with TopHat followed by Cufflinks. qRT–PCR validation was performed using SYBR Green assays. A-to-I (G) RNA editing sites were identified as previously described by Ramaswami G. et al., Nature Methods, 2012 using Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA). RNA editing sites were confirmed by Sanger sequencing. Results: Using an optimized data analysis workflow, we mapped about 30 million sequence reads per sample to the mouse genome (build mm9) and identified 14,484 transcripts in the fetal livers of WT and ADAR1E861A mice with BWA. RNA-seq data had a goodness of fit (R2) of >0.94 between biological triplicates per genotype. Approximately 4.4% of the transcripts showed differential expression between the WT and ADAR1E861A fetal liver, with a LogFC=1.5 and p value <0.05. A profound upregulation of interferon stimulated genes were found to be massively upregulated (up to 11 logFC) in ADAR1E861A fetal liver compared to WT. 6,012 A-to-I RNA editing sites were identified when assessing mismatches in RNA-seq data of WT and ADAR1E861A fetal liver. Conclusions: Our study represents the first detailed analysis of fetal liver transcriptomes and A-to-I RNA editing sites, with biologic replicates, generated by RNA-seq technology. A-to-I RNA editing is the essential function of ADAR1 and is required to suppress interferon signaling to endogenous RNA. Overall design: Fetal liver mRNA profiles of E12.5 wild type (WT) and ADAR E861A mutant mice were generated by deep sequencing, in triplicate, using Illumina HiSeq 200.
Publication Title
RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA was isolated from laser capture micro-dissected (LCM) tumour nests from fresh frozen skin of K14Cre-ER; Ptch1fl/fl; p53fl/fl mice either before (untreated) or after (treated) 28 days of twice a day vismodegib dosing at 75mg/kg body weight by oral gavage. The "SAMPLE_ID" sample characteristic is a sample identifier internal to Genentech. The ID of this project in Genentech's ExpressionPlot database is PRJ0014355 Overall design: Gene expression profiling of tumour cells from BCC mice before and after 28 days of vismodegib treatment
Publication Title
A cell identity switch allows residual BCC to survive Hedgehog pathway inhibition.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Adenosine-to-inosine RNA editing by ADAR1 is essential for normal murine erythropoiesis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Erythroid progenitors purified from EpoRCreR26eYFPADAR1fl/- and EpoRCreR26eYFPADAR1fl/+ control mice were compared for global gene array profiles
Publication Title
Adenosine-to-inosine RNA editing by ADAR1 is essential for normal murine erythropoiesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: RNA editing by ADAR1 is essential for hematopoietic development. The goals of this study were firstly, to identify ADAR1-specific RNA-editing sites by indentifying A-to-I (G) RNA editing sites in wild type mice that were not edited or reduced in editing frequency in ADAR1 deficient murine erythroid cells. Secondly, to determine the transcription consequence of an absence of ADAR1-mediated A-to-I editing. Methods: Total RNA from E14.5 fetal liver of embryos with an erythroid restricted deletion of ADAR1 (KO) and littermate controls (WT), in duplicate. cDNA libraries were prepared and RNA sequenced using Illumina HiSeq2000. The sequence reads that passed quality filters were analyzed at the transcript level with TopHat followed by Cufflinks. qRT–PCR validation was performed using SYBR Green assays. A-to-I (G) RNA editing sites were identified as previously described by Ramaswami G. et al., Nature Methods, 2012 using Burrows–Wheeler Aligner (BWA) followed by ANOVA (ANOVA). RNA editing sites were confirmed by Sanger sequencing. Results: Using an optimized data analysis workflow, we mapped about 30 million sequence reads per sample to the mouse genome (build mm9) and identified 14,484 transcripts in the fetal livers of WT and ADAR1E861A mice with BWA. RNA-seq data had a goodness of fit (R2) of >0.7, p<0.0001 between biological duplicates per genotype. Clusters of hyper-editing were onserved in long, unannotated 3''UTRs of erythroid specific transcripts. A profound upregulation of interferon stimulated genes were found to be massively upregulated (up to 5 log2FC) in KO fetal liver compared to WT. 11.332 (6,894 novel) A-to-I RNA editing sites were identified when assessing mismatches in RNA-seq data. Conclusions: Our study represents the first detailed analysis of erythroid transcriptomes and A-to-I RNA editing sites, with biologic replicates, generated by RNA-seq technology. A-to-I RNA editing is the essential function of ADAR1 and is required to prevent sensing of endogenous transcripts, likely via a RIG-I like receptor mediated axis. Overall design: Fetal liver mRNA profiles of E14.5 wild type (WT) and ADAR Epor-Cre knock out mice were generated by deep sequencing, in duplicate using Illumina HiSeq 2000.
Publication Title
Adenosine-to-inosine RNA editing by ADAR1 is essential for normal murine erythropoiesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
14-3-3 proteins facilitate cytoplasmic-nuclear shuttling of transcription factors.Adipocyte differentiation requires the function of critical transcription factors to drive the development of a mature adipocyte. The aim of the study was to investigate if 14-3-3? is required for the adipogenic transcriptional program. Overall design: Examination of the transcriptome in siCon- and si14-3-3?-transfected 3T3-L1 cells undergoing differentiation at t=0, 24, and 48 hours.
Publication Title
14-3-3ζ coordinates adipogenesis of visceral fat.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA was isolated from fluorescence activated cell sorted (FACS) Lgr5-GFP+ and Lgr5-GFP- from aged matched subcutaneously implanted Apcmin/+;KrasLSL-G12D/+;VillinCre; Lgr5DTReGFP;p53KO (AKVPL) and Apcmin/+;KrasLSL-G12D/+;VillinCre; Lgr5DTReGFP;p53KO;SMAD4KO (AKVPSL) intestinal tumours. "SAMPLE_ID" sample characteristic is a sample identifier internal to Genentech. The ID of this project in Genentech''s ExpressionPlot database is PRJ0009421 Overall design: Gene expression profiling of Lgr5+ and Lgr5- tumour cells from AKVPL and AKVPSL murine derived intestinal tumours
Publication Title
A distinct role for Lgr5<sup>+</sup> stem cells in primary and metastatic colon cancer.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina HiSeq 2500
Description
Due to inherent differences in adipcoyte size between wildtype and knockout animals, we sought to examine if the decrease in adipocyte size was due to differences in the transcriptome and more specifcially, adipogenic genes. Overall design: Examination of the transcriptome in wildtype (WT) and knockout (KO) gonadal white adipose tissue from adult mice
Publication Title
14-3-3ζ coordinates adipogenesis of visceral fat.
Sample Metadata Fields
No sample metadata fields
View Samples