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accession-icon SRP127343
Systematic functional characterization of BAF mutations yields novel intra-complex synthetic lethalities [RNA-Seq]
  • organism-icon Homo sapiens
  • sample-icon 72 Downloadable Samples
  • Technology Badge IconIllumina HiSeq 4000

Description

Aberrations in genes coding for subunits of the BAF chromatin remodeling complex are highly abundant in human cancers. Currently, it is not understood how these loss-of-function mutations contribute to cancer development and how they can be targeted therapeutically. The cancer type specific occurrence patterns of certain subunit mutations suggest subunit-specific effects on BAF complex function, possibly by the formation of aberrant residual complexes. Here, we systematically characterize the effects of individual subunit loss on complex composition, chromatin accessibility and gene expression in a panel of knock-out cell lines deficient for 22 targetable BAF subunits. We observe strong, specific and often discordant alterations dependent on the targeted subunit and show that these explain intra-complex co-dependencies, including the novel synthetic lethal interactions SMARCA4-ARID2, SMARCA4-ACTB and SMARCC1-SMARCC2. These data provide insights into the role of different BAF subcomplexes in genome-wide chromatin organization and suggest novel approaches to therapeutically target BAF mutant cancers. Overall design: RNA-seq samples for knockouts of BAF complex in the HAP1 cell line.

Publication Title

Systematic characterization of BAF mutations provides insights into intracomplex synthetic lethalities in human cancers.

Sample Metadata Fields

Cell line, Subject

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accession-icon GSE49439
Differentiation of human amniotic fluid kidney progenitor cells into podocytes and comparison with human conditionally immortalized podocytes
  • organism-icon Homo sapiens
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 1.0 ST Array (hugene10st)

Description

In this work, we isolated and characterized a novel cell population derived from human amniotic fluid cells (hAKPC-P), and we differentiated them into podocytes.

Publication Title

A novel source of cultured podocytes.

Sample Metadata Fields

Specimen part, Cell line

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accession-icon GSE46880
RNA methylation destabilizes developmental regulators in murine embryonic stem cells
  • organism-icon Mus musculus
  • sample-icon 18 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 2.0 ST Array (mogene20st), Illumina HiSeq 2000

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells.

Sample Metadata Fields

Cell line, Treatment, Time

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accession-icon GSE46879
RNA methylation destabilizes developmental regulators in murine embryonic stem cells (MoGene-2)
  • organism-icon Mus musculus
  • sample-icon 26 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 2.0 ST Array (mogene20st)

Description

Recent methylome studies have located N6-methyladenosine (m6A) RNA modification on thousands of mammalian transcripts. However, its functional mechanism remains unclear. In this study, we examined the role of m6A methylation in mouse embryonic stem cells.

Publication Title

N6-methyladenosine modification destabilizes developmental regulators in embryonic stem cells.

Sample Metadata Fields

Cell line, Treatment, Time

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accession-icon SRP136794
DNA methylation in neurons from post-mortem brains in schizophrenia and bipolar disorder (RNA-Seq)
  • organism-icon Homo sapiens
  • sample-icon 32 Downloadable Samples
  • Technology Badge IconNextSeq 500

Description

We fine-mapped DNA methylation in neuronal nuclei (NeuN+) isolated by flow cytometry from post-mortem frontal cortex of the brain of individuals diagnosed with schizophrenia, bipolar disorder, and controls (n=29, 26, and 28 individuals). Overall design: Brain tissue samples (n=34 human samples, 17 case and 17 control) were lysed using QIAzol Lysis Reagent (Qiagen) and homogenized with a TissueLyser (Qiagen). Total RNA from each sample was isolated using the RNeasy Plus Universal Mini kit (Qiagen) according to manufacturer's instructions and included an enzymatic DNase (Qiagen) digestion step. RNA quality was measured on a 2100 Bioanalyzer (Agilent) and quantity was determined with a Nanodrop 2000 spectrophotometer (Thermo Fisher Scientific). Only RNA samples with a RIN quality score >7 proceeded to RNA-seq library preparation (RIN between 7.1 to 9.4 for all samples). Libraries were prepared by the Van Andel Genomics Core from 300 ng of total RNA using the KAPA RNA HyperPrep Kit with RiboseErase (v1.16) (Kapa Biosystems). RNA was sheared to 300-400 bp. Prior to PCR amplification, cDNA fragments were ligated to Bio Scientific NEXTflex Adapters (Bioo Scientific). Quality and quantity of the finished libraries were assessed using a combination of Agilent DNA High Sensitivity chip (Agilent Technologies, Inc.), QuantiFluor® dsDNA System (Promega Corp.), and Kapa Illumina Library Quantification qPCR assays (Kapa Biosystems). Individually indexed libraries were pooled, and 75 bp paired-end sequencing was performed on an Illumina NextSeq 500 sequencer, with all libraries run across 3 flowcells. Base calling was done by Illumina NextSeq Control Software (NCS) v2.0 and output of NCS was demultiplexed and converted to FastQ format with Illumina Bcl2fastq v1.9.0. Trimgalore (v0.11.5) was used for adapter removal prior to genome alignment. STAR33 (v2.3.5a) index was generated using Ensemble GRCh38 p10 primary assembly genome and the Gencode v26 primary assembly annotation. Read alignment was performed using a STAR two-pass mode. Gene counts matrix was imported into R (3.4.1) and low expressed genes (counts per million (CPM) < 1 in all samples) were removed prior to differential expression in EdgeR. Gene counts were normalized using the trimmed mean of M-values, fitted in a generalized linear model and differentially tested using a likelihood ratio test. The generalized linear model contained covariates age, sex, post mortem interval and neuronal cell composition. Cell-type compositions for each sample was accessed using CIBERSORT34 on normalized sample counts against cell-type specific markers, identifying the proportion of neurons in each samples. Benjamini Hochberg correction was used to adjust for multiple testing.

Publication Title

Differential methylation of enhancer at IGF2 is associated with abnormal dopamine synthesis in major psychosis.

Sample Metadata Fields

Sex, Age, Race, Subject

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accession-icon GSE98902
Effect of Analytic Treatment Interruption of Antiretroviral Therapy on HIV Reservoirs and Immunological Parameters
  • organism-icon Homo sapiens
  • sample-icon 28 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U219 Array (hgu219)

Description

We compared transcriptional profiles of CD4+ and CD8+ T lymphocytes from HIV infected individuals before and 1 year after interruption of antiretroviral therapy (ART).

Publication Title

Effect of analytical treatment interruption and reinitiation of antiretroviral therapy on HIV reservoirs and immunologic parameters in infected individuals.

Sample Metadata Fields

Sex, Age, Specimen part, Disease stage, Race, Subject

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accession-icon GSE28953
Pseudomonas aeruginosa two-component regulator BfmR controls bacteriophage lysis and DNA release during biofilm development through PhdA
  • organism-icon Pseudomonas aeruginosa
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Pseudomonas aeruginosa Array (paeg1a)

Description

Biofilms are surface-adhered bacterial communities encased in an extracellular matrix composed of polysaccharides, proteins, and extracelluar (e)DNA, with eDNA being required for the formation and integrity of biofilms. Here we demonstrate that the spatial and temporal release of eDNA is regulated by BfmR, a regulator essential for Pseudomonas aeruginosa biofilm development. The expression of bfmR coincided with localized cell death and DNA release, with high eDNA concentrations localized to the outer part of microcolonies in the form of a ring and as a cap on small clusters. Additionally, eDNA release and cell lysis increased significantly following bfmR inactivation. Genome-wide transcriptional profiling indicated that bfmR was required for repression of genes associated with bacteriophage assembly and bacteriophage-mediated lysis. In order to determine which of these genes were directly regulated by BfmR, we utilized chromatin immunoprecipitation (ChIP) analysis to identify the promoter of PA0691, termed here phdA, encoding a previously undescribed homologue of the prevent-host-death (Phd) family of proteins. Lack of phdA expression coincided with impaired biofilm development, increased cell death and bacteriophage release, a phenotype comparable to bfmR. Expression of phdA in bfmR biofilms restored eDNA release, cell lysis, release of bacteriophages, and biofilm formation to wild type levels. Moreover, overexpression of phdA rendered P. aeruginosa resistant to lysis mediated by superinfective bacteriophage Pf4 which was only detected in biofilms. The expression of bfmR was stimulated by conditions resulting in membrane perturbation and cell lysis. Thus, we propose that BfmR regulates biofilm development by controlling bacteriophage-mediated lysis and thus, cell death and eDNA release, via PhdA.

Publication Title

The novel Pseudomonas aeruginosa two-component regulator BfmR controls bacteriophage-mediated lysis and DNA release during biofilm development through PhdA.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE35286
Microcolony formation by the opportunistic pathogen Pseudomonas aeruginosa requires pyruvate and pyruvate fermentation.
  • organism-icon Pseudomonas aeruginosa
  • sample-icon 6 Downloadable Samples
  • Technology Badge Icon Affymetrix Pseudomonas aeruginosa Array (paeg1a)

Description

A hallmark of the biofilm architecture is the presence of microcolonies. However, little is known about the underlying mechanisms governing microcolony formation. In the human pathogen Pseudomonas aeruginosa, microcolony formation is dependent on the two-component regulator MifR, with mifR mutant biofilms exhibiting an overall thin structure lacking microcolonies, and overexpression of mifR resulting in hyper-microcolony formation. Here, we made use of the distinct MifR-dependent phenotypes to elucidate mechanisms associated with microcolony formation. Using global transcriptomic and proteomic approaches, we demonstrate that cells located within microcolonies experience stressful, oxygen limited, and energy starving conditions, as indicated by the activation of stress response mechanisms and anaerobic and fermentative processes, in particular pyruvate fermentation. Inactivation of genes involved in pyruvate utilization including uspK, acnA and ldhA abrogated microcolony formation in a manner similar to mifR inactivation. Moreover, depletion of pyruvate from the growth medium impaired biofilm and microcolony formation, while addition of pyruvate significantly increased microcolony formation. Addition of pyruvate partly restored microcolony formation in mifR biofilms. Moreover, addition of pyruvate to or expression of mifR in lactate dehydrogenase (ldhA) mutant biofilms did not restore microcolony formation. Consistent with the finding of denitrification genes not demonstrating distinct expression patterns in biofilms forming or lacking microcolonies, addition of nitrate did not alter microcolony formation. Our findings indicate the fermentative utilization of pyruvate to be a microcolony-specific adaptation to the oxygen limitation and energy starvation of the P. aeruginosa biofilm environment.

Publication Title

Microcolony formation by the opportunistic pathogen Pseudomonas aeruginosa requires pyruvate and pyruvate fermentation.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE13869
Transcriptome of the Nxnl1-/- mouse retina
  • organism-icon Mus musculus
  • sample-icon 8 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

Rod-derived Cone Viability Factor (RdCVF, alias nxnl1) is a retina-specific protein identified for its therapeutic potential in supporting cone survival during retinal degeneration.

Publication Title

The disruption of the rod-derived cone viability gene leads to photoreceptor dysfunction and susceptibility to oxidative stress.

Sample Metadata Fields

Disease, Disease stage

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accession-icon GSE114026
7-month-old mdx mouse hearts wild-type and deficient for cardiomyocyte-specific IKK
  • organism-icon Mus musculus
  • sample-icon 7 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

NF-κB inhibition rescues cardiac function by remodeling calcium genes in a Duchenne muscular dystrophy model.

Sample Metadata Fields

Age

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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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