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accession-icon E-MTAB-991
Transcription profiling by array of human colon cancer xenografted in immunodeficient mice and rats to investigate clinical heterogeneity
  • organism-icon Homo sapiens
  • sample-icon 115 Downloadable Samples
  • Technology Badge Icon Affymetrix HT Human Genome U133A Array (hthgu133a)

Description

Patient-derived xenograft models are considered to represent the heterogeneity of human cancers and might be more relevant preclinical models to evaluate effective therapeutic agents. Our consortium joins efforts to extensively develop and characterize a new collection of patient-derived colorectal cancer models. From 86 unsupervised surgical colon sample collection, 54 tumors were successfully xenografted in immunodeficient mice and rats, representing 35 primary tumors, 5 peritoneal carcinosis and 14 metastases. Our histological and molecular characterization of patient tumors, first passage on mice and later passages includes the sequence of key genes involved in CRC (ie APC, KRAS, TP53), CGH array and transcriptomic analysis. This comprehensive characterization demonstrates that our collection recapitulates the clinical situation regarding the histopathological and molecular diversity of colorectal cancers. Moreover, patient tumors and corresponding models are clustering together which gives the opportunity to look for relevant signatures and comparison studies between clinical and preclinical data. Hence, we performed pharmacological monotherapy studies with standard of care for colon cancer (5-FU, oxaliplatin, irinotecan, cetuximab). Through this extensive in vivo analysis, we have compared the molecular profile with the drug sensitivity of each tumor models, and run an equivalent of a cetuximab phase II clinical trial in a preclinical setting. Our results confirm the key role of KRAS mutation in the cetuximab resistance and demonstrate that such collection could bring benefit to evaluate novel targeted therapeutic strategies and potentially help the stratification strategy for cancer patients according to molecular marker. This set correspond to 82 CGH profiles, with 7 samples from patient tumor and 75 samples from mouse xenograft at different passages P0 to P9. All hybridizations are performed with Human CGH 244K Agilent arrays (amadid 014693) in dual color with Human DNA Promega (sex matched) as reference. ID for biosources without an -Px suffix correspond to tumor patients. ID with a suffix correspond to xenograft with 0 for the first passage.

Publication Title

Characterization of a large panel of patient-derived tumor xenografts representing the clinical heterogeneity of human colorectal cancer.

Sample Metadata Fields

Specimen part, Disease, Disease stage, Time

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accession-icon GSE16040
S. pombe genome-wide nucleosome mapping reveals positioning mechanisms distinct from S. cerevisiae
  • organism-icon Schizosaccharomyces pombe
  • sample-icon 5 Downloadable Samples
  • Technology Badge Icon Affymetrix Yeast Genome 2.0 Array (yeast2)

Description

Positioned nucleosomes limit the access of proteins to DNA and implement regulatory features encoded in eukaryotic genomes. Here we generated the first genome-wide nucleosome positioning map for Schizosaccharomyces pombe and annotated transcription start and termination sites genome-wide. Using this resource we found surprising differences compared to the nucleosome organization in the distantly related yeast Saccharomyces cerevisiae [the cerevisiae data has been published by others (PMID: 17873876) and the raw data is deposited at ArrayExpress(E-MEXP-1172)]. DNA sequence guides nucleosome positioning differently, e.g., poly(dA:dT) elements are not enriched in S. pombe nucleosome-depleted regions (NDRs). Regular nucleosomal arrays emanate more asymmetrically, i.e., mainly co-directionally with transcription, from promoter NDRs, but promoters harbouring the histone variant H2A.Z show regular arrays also upstream. Regular nucleosome phasing in S. pombe has a very short repeat length of 154 base pairs, and requires a remodeler, Mit1, conserved in humans but not found in S. cerevisiae. Nucleosome positioning mechanisms are evidently not universal but evolutionarily plastic.

Publication Title

Schizosaccharomyces pombe genome-wide nucleosome mapping reveals positioning mechanisms distinct from those of Saccharomyces cerevisiae.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE30219
"Off-context" gene expression in lung cancer identifies a group of metastatic-prone tumors
  • organism-icon Homo sapiens
  • sample-icon 299 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

An unexplored consequence of epigenetic alterations associated with cancer is the ectopic expression of tissue-restricted genes. Here, a new strategy was developed to decipher genome-wide expression data in search for these off-context gene activations, which consisted first, in identifying a large number of tissue-specific genes normally epigenetically silenced in most somatic cells and second, in using them as cancer biomarkers on an on/off basis. Applying this concept to analyze whole-genome transcriptome data in lung cancer, we discovered a specific group of 26 genes whose expression was a strong and independent predictor of poor prognosis in our cohort of 293 lung tumours, as well as in two independent external populations. In addition, these 26 classifying genes enabled us to isolate a homogenous group of metastatic-prone highly aggressive tumours, whose characteristic gene expression profile revealed a high proliferative potential combined to a significant decrease in immune and signaling functions. This work illustrates a new approach for a personalized management of cancer, with applications to any cancer type.

Publication Title

Ectopic activation of germline and placental genes identifies aggressive metastasis-prone lung cancers.

Sample Metadata Fields

Sex, Specimen part

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accession-icon GSE104224
Two distinct myeloid subsets at the term human fetal-maternal interface
  • organism-icon Homo sapiens
  • sample-icon 11 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 1.0 ST Array (hugene10st)

Description

The subsets of immune cells within the human placenta are incompletely described. We used microarray to determine the transcriptional differences between two myeloid subsets in the term human placenta.

Publication Title

Two Distinct Myeloid Subsets at the Term Human Fetal-Maternal Interface.

Sample Metadata Fields

Specimen part

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accession-icon GSE35627
Expression data from Angiotensin II (Ang II)-treated Rat Vascular Smooth Muscle Cells (RVSMC)
  • organism-icon Rattus norvegicus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Rat Gene 1.0 ST Array (ragene10st)

Description

Angiotensin II (Ang II)-mediated vascular smooth muscle cells (VSMC) dysfunction plays a critical role in cardiovascular diseases. However, the gene expression in this process is unclear.

Publication Title

Small RNA sequencing reveals microRNAs that modulate angiotensin II effects in vascular smooth muscle cells.

Sample Metadata Fields

Specimen part, Time

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accession-icon SRP010854
High-throughput sequencing of endogenous small RNAs from rat vascular smooth muscle cells with and without Angiotensin II stimulation
  • organism-icon Rattus norvegicus
  • sample-icon 4 Downloadable Samples
  • Technology Badge IconIllumina Genome Analyzer IIx

Description

Angiotensin II (Ang II)-mediated vascular smooth muscle cells (VSMC) dysfunction plays a critical role in cardiovascular diseases. However, the role of microRNAs (miRNAs) in this process is unclear. We used small RNA deep sequencing to profile Ang II-regulated miRNAs in rat VSMC and evaluated their role in VSMC dysfunction. Sequencing results revealed several Ang II-responsive miRNAs and bioinformatics analysis showed that their predicted targets can modulate biological processes relevant to cardiovascular diseases. Overall design: Examined 4 samples of Rat VSMC. Control (without Ang II treatment) and 3 samples treated with Ang II for 1h, 3h, and 24h. Compared the changes in gene expression in Ang II treated samples relative to control samples.

Publication Title

Small RNA sequencing reveals microRNAs that modulate angiotensin II effects in vascular smooth muscle cells.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE67051
Gene expression analysis in EGFR-mutant NSCLC cells treated with erlotinib versus DMSO
  • organism-icon Homo sapiens
  • sample-icon 10 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

This experiment is designed to detect genes differentially expressed in 2uM erlotinib treatment versus DMSO treatment and to identify differential gene set enrichments.

Publication Title

Inhibition of Casein Kinase 1 Alpha Prevents Acquired Drug Resistance to Erlotinib in EGFR-Mutant Non-Small Cell Lung Cancer.

Sample Metadata Fields

Specimen part, Cell line

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accession-icon SRP035473
RNA-seq analysis of diabetes induced changes in macrophage transcriptome
  • organism-icon Mus musculus
  • sample-icon 4 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

Macrophage dysfunction and polarization plays key role in chronic inflammation associated with diabetes and its complications. However, the effect of diabetes on macrophage transcriptome including long non-coding RNAs is not known. Here, we analyzed global changes in transcriptome of bone marrow macrophages isolated from type 2 diabetic db/db mice and control littermates db/+ mice using high throughput RNA-seq technique. Data analysis showed that expression of genes relevant to fibrosis, cell adhesion and inflammation were altered in diabetic db/db mice relative to control db/+ mice. Furthermore, expression of several known and novel long non coding RNAs and nearby genes was altered in db/db mice. Gene ontology and IPA showed activation of signaling netwroks relevant to fibrosis, cell adhesion and inflammatory pathways . This study for the first time demonstrated that diabetes profoundly affects macrophage transcriptome including expression of long non coding RNAs and altered the levels of genes relevant to diabetes complications. Overall design: Bone marrow macrophages were isolated from 12 weeks old type 2 diabetic male db/db mice and control littermates db/+ mice. These were differentiated in culture for 7-8 days in the presence of 10 ng/ml of MCSF-1 (BMMC) or 20 ng/ml of GM-CSF (BMGM). Then RNA was extracted and used for RNA-seq.

Publication Title

Regulation of inflammatory phenotype in macrophages by a diabetes-induced long noncoding RNA.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE7253
Puberty and Diabetes in the Kidney
  • organism-icon Rattus norvegicus
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Rat Genome 230 2.0 Array (rat2302)

Description

Puberty unmasks or accelerates nephropathies, including the nephropathy of diabetes mellitus (DM). A number of cellular systems implicated in the kidney disease of DM interweave, forming an interdependent functional web. We performed focused microarray analysis to test the hypothesis that one or more genes in the transforming growth factor beta (TGF-) signaling system would be differentially regulated in male rats depending on the age of onset of DM.

Publication Title

Prepubertal onset of diabetes prevents expression of renal cortical connective tissue growth factor.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE81721
Autophagy maintains metabolism and functional activity of a subset of aged hematopoietic stem cells
  • organism-icon Mus musculus
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Autophagy maintains the metabolism and function of young and old stem cells.

Sample Metadata Fields

Specimen part

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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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