Expression profiles for Gfap-positive astrocytes obtained by in vitro differentiation of 129SvJae x C57BL/6 murine embryonic stem (ES) cells. Generated to examine the relationship between expression levels and DNA methylation patterns.
Genome-scale DNA methylation maps of pluripotent and differentiated cells.
No sample metadata fields
View SamplesRNA-Seq is an effective method to study the transcriptome, but can be difficult to apply to scarce or degraded RNA from fixed clinical samples, rare cell populations, or cadavers. Recent studies have proposed several methods for RNA-Seq of low quality and/or low quantity samples, but their relative merits have not been systematically analyzed. Here, we compare five such methods using a comprehensive set of metrics, relevant to applications such as transcriptome annotation, transcript discovery, and gene expression. Using a single human RNA sample, we constructed and deeply sequenced 10 libraries with these methods and two control libraries. We find that the RNase H method performed best for low quality RNA, and can even effectively replace oligo (dT) based methods for standard RNA-Seq. SMART and NuGEN had distinct strengths for low quantity RNA. Our analysis allows biologists to select the most suitable methods and provides a benchmark for future method development. Overall design: Examination of 9 different RNA-Seq libraries starting from total RNA from 5 distinct methods; also 3 control RNA-Seq libraries
Comparative analysis of RNA sequencing methods for degraded or low-input samples.
Specimen part, Cell line, Subject
View SamplesAs part of a large genetic evolution study we also acquired 3'UTR expression arrays at two time points for the same 18 patients with CLL.
Evolution and impact of subclonal mutations in chronic lymphocytic leukemia.
Specimen part, Disease, Disease stage, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrative analysis of the melanoma transcriptome.
Disease, Disease stage
View SamplesPaired end sequencing of cDNA isolated from individual melanoma samples via the Illumina sequencing platform to identify genetic aberrations that may play a role in melanoma genesis.
Integrative analysis of the melanoma transcriptome.
No sample metadata fields
View SamplesWe profiled the gene expression levels from 8 melanoma short-term cultures and 1 melanoma cell line in order to compare to expression level estimates obtained by RNA-seq.
Integrative analysis of the melanoma transcriptome.
Disease, Disease stage
View SamplesThe incidence of esophageal adenocarcinoma (EAC) has risen 600% over the last 30 years. With an extremely poor five-year survival rate of only 15%, identification of new therapeutic targets for EAC is of great importance. Here, we analyze the mutation spectra from the whole exome sequencing of 149 EAC tumors/normal pairs, 15 of which have also been subjected to whole genome sequencing. We identify a novel mutational signature in EACs defined by a high prevalence of A to C transversions at Ap*A dinucleotides. Statistical analysis of the exome data identified 26 genes that are mutated at a significant frequency. Of these 26 genes, only four (TP53, CDKN2A, SMAD4, and PIK3CA) have been previously implicated in EAC. The novel significantly mutated genes include several chromatin modifying factors and candidate contributors to EAC: SPG20, TLR4, ELMO1, and DOCK2. Notably, functional analyses of EAC-derived mutations in ELMO1 increase cellular invasion. Therefore, we suggest a new hypothesis about the potential activation of the RAC1 pathway to be a contributor to EAC tumorigenesis.
Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity.
Sex, Age, Specimen part, Disease stage, Race
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Initial genome sequencing and analysis of multiple myeloma.
Specimen part, Disease, Disease stage
View SamplesThe MMRC reference collection is a dataset of gene expression profiling, array comparative genomic hybridization, and re-sequencing created as a resource for the Multiple Myeloma research community.
Initial genome sequencing and analysis of multiple myeloma.
Specimen part
View SamplesGlioblastoma multiforme (GBM) is the most malignant and most common tumor of the central nervous system characterized by rapid growth and extensive tissue infiltration. GBM results in more years of life lost than any other cancer type. Notch signaling has been implicated in GBM pathogenesis through several modes of action. Inhibition of Notch leads to a reduction of cancer-initiating cells in gliomas and reduces proliferation and migration. Deltex1 (DTX1) is part of an alternative Notch signaling pathway distinct from the canonical MAML1/RBPJ-mediated cascade. In this study, we show that DTX1 activates both the RTK/PI3K/PKB as well as the MAPK/ERK pathway. Moreover, we found the anti-apoptotic factor Mcl-1 to be induced by DTX1. In accordance with this, the clonogenic potential and proliferation rates of glioma cell lines correlated with DTX1 levels. DTX1 knock down mitigated the tumorigenic potential in vivo, and overexpression of DTX1 increased cell migration and invasion of tumor cells accompanied by an elevation of the pro-migratory factors PKB and Snail1. Microarray gene expression analysis identified a DTX1-specific transcriptional program - including microRNA-21 - which is distinct from the canonical Notch signaling. We propose the alternative Notch pathway via DTX1 as oncogenic factor in malignant glioma and found low DTX1 expression levels to correlate with prolonged survival of GBM and early breast cancer patients in open source databases.
Deltex-1 activates mitotic signaling and proliferation and increases the clonogenic and invasive potential of U373 and LN18 glioblastoma cells and correlates with patient survival.
Specimen part, Cell line
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