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accession-icon SRP147452
Genetic and transcriptional variation alters cancer cell line drug response [MCF7 strain L]
  • organism-icon Homo sapiens
  • sample-icon 3 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2500

Description

10X Genomics single cell RNAseq of MCF7 cells Human cancer cell lines are the workhorse of cancer research. While cell lines are known to evolve in culture, the extent of the resultant genetic and transcriptional heterogeneity and its functional consequences remain understudied. Here, genomic analyses of 106 cell lines grown in two laboratories revealed extensive clonal diversity. Follow-up comprehensive genomic characterization of 27 strains of the common breast cancer cell line MCF7 uncovered rapid genetic diversification. Similar results were obtained with multiple strains of 13 additional cell lines. Importantly, genetic changes were associated with differential activation of gene expression programs and marked differences in cell morphology and proliferation. Barcoding experiments showed that cell line evolution occurs as a result of positive clonal selection that is highly sensitive to culture conditions. Analyses of single cell-derived clones showed that ongoing instability quickly translates into cell line heterogeneity. Testing of the 27 MCF7 strains against 321 anti-cancer compounds uncovered strikingly disparate drug response: at least 75% of compounds that strongly inhibited some strains were completely inactive in others. This study documents the extent, origin and consequence of genetic variation within cell lines, and provides a framework for researchers to measure such variation in efforts to support maximally reproducible cancer research. Overall design: Single cell clones were derived from MCF7 cells (strain L) and cultured.

Publication Title

Genetic and transcriptional evolution alters cancer cell line drug response.

Sample Metadata Fields

Specimen part, Subject

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accession-icon GSE34023
Overexpression of BglJ and LeuO in Escherichia coli K12
  • organism-icon Escherichia coli k-12
  • sample-icon 27 Downloadable Samples
  • Technology Badge Icon Affymetrix E. coli Genome 2.0 Array (ecoli2)

Description

The only target locus of transcription factor BglJ known to date is the bgl operon, and activation of bgl by BglJ requires RcsB. Transcription factor LeuO is involved in stress responses and known as antagonist of H-NS. To identifiy novel targets of BglJ, we overexpressed BglJ in Escherichia coli K12 and measured differential gene expression by performing DNA microarray analysis. Moreover, to analyze whether all targets of BglJ require RcsB, we overexpressed BglJ in an rcsB deletion background. In addition, we overexpressed LeuO to identifiy targets of LeuO.

Publication Title

RcsB-BglJ activates the Escherichia coli leuO gene, encoding an H-NS antagonist and pleiotropic regulator of virulence determinants.

Sample Metadata Fields

No sample metadata fields

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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 GSE2466
B_Cell_Chronic_Lymphocytic_Leukemia
  • organism-icon Homo sapiens
  • sample-icon 111 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U95A Array (hgu95a)

Description

We used high density oligonucleotide arrays to identify molecular correlates of genetically and clinically distinct subgroups of B-cell chronic lymphocytic leukemia (B-CLL). Gene expression profiling was used to profile the five most frequent genomic aberrations, namely deletions affecting chromosome bands 13q14, 11q22-q23, 17p13 and 6q21, and gains of genomic material affecting chromosome band 12q13. A strikingly high degree of correlation between loss or gain of genomic material and the amount of transcripts from the affected regions leads to the hypothesis of gene dosage as a significant pathogenic factor. Furthermore, the influence of the immunoglobulin variable heavy chain (VH) mutation status was determined. A clear distinction in the expression profiles of unmutated and mutated VH samples exists, which can be discovered using unsupervised learning methods. However, when samples were separated by gender, this separation could only be detected in samples from male patients.

Publication Title

Microarray gene expression profiling of B-cell chronic lymphocytic leukemia subgroups defined by genomic aberrations and VH mutation status.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE141873
Establishment and Characterisation by Expression Microarray of Patient Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients
  • organism-icon Homo sapiens
  • sample-icon 21 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 2.0 ST Array (hugene20st)

Description

mRNA expression profiling of pancreatic cancer, comparing adjacent normal tissue, patient tumour and first generation patient derived xenograft tumours

Publication Title

Establishment and Characterisation by Expression Microarray of Patient-Derived Xenograft Panel of Human Pancreatic Adenocarcinoma Patients.

Sample Metadata Fields

Specimen part

View Samples
accession-icon GSE101141
Amniotic fluid transcriptomics reflects novel disease mechanisms in fetuses with myelomeningocele
  • organism-icon Homo sapiens
  • sample-icon 20 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

To identify molecular pathophysiologic changes and novel disease mechanisms specific to myelomeningocele by analyzing AFS cfRNA in fetuses with open myelomeningocele.

Publication Title

Amniotic fluid transcriptomics reflects novel disease mechanisms in fetuses with myelomeningocele.

Sample Metadata Fields

No sample metadata fields

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accession-icon SRP125027
Transcriptional profiling of macrophages derived from injured nerves at 3 and 8 days post-injury
  • organism-icon Mus musculus
  • sample-icon 6 Downloadable Samples
  • Technology Badge IconNextSeq 500

Description

Pro-regenerative macrophages are well known for their role in promoting tissue repair, however in nerve injury their role in promoting regenerative events is not well defined. Macrophage-targeted RNAseq revealed that macrophages expressed an array of ligands post nerve injury that interact with the injury environement to regulate regeneration. Overall design: RNAseq experiment was performed on FACS-collected cells obtained from the nerves of adult female mice (n=7-8 per time point at Day 3 and 8 post-nerve injury) from a double macrophage reporter (Cx3cr1-GFP/Ccr2-RFP) mouse line (stock no.: 017586; stock No.: 005582, Jackson Laboratories). Samples were pooled to obtain 2 RNAseq sample replicates per time point. Monocytes were also included as a reference.

Publication Title

Macrophages Regulate Schwann Cell Maturation after Nerve Injury.

Sample Metadata Fields

Sex, Age, Specimen part, Cell line, Subject

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accession-icon GSE15940
Sex-Dependent Programming of Glucose and Fatty Acid Metabolism in Mouse Offspring by Maternal Protein Restriction
  • organism-icon Mus musculus
  • sample-icon 32 Downloadable Samples
  • Technology Badge IconIllumina mouseRef-8 v1.1 expression beadchip

Description

Analysis of glucose and Lipid metabolism in male and female offspring after protein restriction of the mother

Publication Title

Sex-dependent programming of glucose and fatty acid metabolism in mouse offspring by maternal protein restriction.

Sample Metadata Fields

Sex, Specimen part

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accession-icon SRP061785
RGS9-2-controlled adaptations in the striatum determine the onset of action and eficacy of antidepressants in neuropathic pain states
  • organism-icon Mus musculus
  • sample-icon 18 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 2000

Description

The striatal protein Regulator of G protein signaling-2 (RGS9-2) plays a key modulatory role in opioid, monoamine and other GPCR responses. Here, we use the murine spared-nerve injury model of neuropathic pain to investigate the mechanism by which RGS9-2 in the nucleus accumbens (NAc), a brain region involved in mood reward and motivation, modulates the actions of tricyclic antidepressants (TCAs). Prevention of RGS9-2 action in the NAc increases the efficacy of the TCA desipramine and dramatically accelerates its onset of action. By controlling the activation of effector molecules by G protein a and bg subunits, RGS9-2 affects several protein interactions, phosphoprotein levels, and the function of the epigenetic modifier histone deacetylase 5 (HDAC5), that are important for TCA responsiveness. Furthermore, information from RNA-seq analysis reveals that RGS9-2 in the NAc affects the expression of many genes known to be involved in nociception, analgesia and antidepressant drug actions. Our findings provide novel information on NAc-specific cellular mechanisms that mediate the actions of TCAs in neuropathic pain states. Overall design: The RNAseq study was designed in order to reveal the impact of RGS9-2 on gene regulation in the Nucleus Accumbens under neuropathic pain and antidepressant treatment conditions. A total of 18 samples was used, coprising 6 different groups , and each group consisted of three different biological replicates.

Publication Title

RGS9-2--controlled adaptations in the striatum determine the onset of action and efficacy of antidepressants in neuropathic pain states.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE51370
Investigation of radiosensitivity gene signatures in cancer cell lines
  • organism-icon Homo sapiens
  • sample-icon 11 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Commercially available cell lines derived from Head and Neck Squamous cell carcinoma (HNSCC) were cultured and baseline gene expression values were assayed.

Publication Title

Investigation of radiosensitivity gene signatures in cancer cell lines.

Sample Metadata Fields

No sample metadata fields

View Samples
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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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