The effect of drugs, disease and other perturbations on mRNA levels are studied using gene expression microarrays or RNA-seq, with the goal of understanding molecular effects arising from the perturbation. Previous comparisons of reproducibility across laboratories have been limited in scale and focused on a single model. The use of model systems, such as cultured primary cells or cancer cell lines, assumes that mechanistic insights derived with would have been observed via in vivo studies. We examined the concordance of compound-induced transcriptional changes using data from several sources: rat liver and rat primary hepatocytes (RPH) from Drug Matrix (DM) and open TG-GATEs (TG), primary human hepatocytes (HPH) from TG, and mouse liver / HepG2 results from the Gene Expression Omnibus (GEO) repository. Gene expression changes for treatments were normalized to controls and analyzed with three methods: 1) gene level for 9071 high expression genes in rat liver, 2) gene set analysis (GSA) using canonical pathways and gene ontology sets, 3) weighted gene co-expression network analysis (WGCNA). Co-expression networks performed better than genes or GSA on a quantitative metric when comparing treatment effects within rat liver and rat vs. mouse liver. Genes and modules performed similarly at Connectivity Map-style analyses, where success at identifying similar treatments among a collection of reference profiles is the goal. Comparisons between rat liver and RPH, and those between RPH, HPH and HepG2 cells reveal low concordance for all methods. We investigate differences in the baseline state of cultured cells in the context of drug-induced perturbations in rat liver and highlight the striking similarity between toxicant-exposed cells in vivo and untreated cells in vitro.
Assessing Concordance of Drug-Induced Transcriptional Response in Rodent Liver and Cultured Hepatocytes.
Sex, Specimen part
View SamplesLoss of function of FMR2 due to either hypermethylation of the CpG island as a consequence of the expansion of the CCG repeat near its transcription start site, or internal deletion of FMR2 is considered to be the major cause of FRAXE fragile site associated intellectual disability. FMR2 was shown to be a potent transcription activator as well as an RNA binding protein capable of regulating alternative splicing.
Loss of FMR2 further emphasizes the link between deregulation of immediate early response genes FOS and JUN and intellectual disability.
No sample metadata fields
View SamplesToca 511 is a modified Retroviral Replicating Vector based on Moloney g-retrovirus with an amphotropic envelope. As an investigational cancer treatment, Toca 511 preferentially infects cancer cells without direct cell lysis and encodes an enhanced yeast cytosine deaminase that converts the antifungal drug 5-fluorocytosine to the anticancer drug, 5-fluorouracil. A panel of established human cancers cell lines, derived from glioblastoma, colon, and breast cancer tissue was used to evaluate parameters critical for effective anticancer activity. As part of these analyses, we profiled relative mRNA levels across these cell lines via RNA sequencing. Overall design: mRNA expression profiles across nine human cancer cell lines.
Retroviral Replicating Vectors Deliver Cytosine Deaminase Leading to Targeted 5-Fluorouracil-Mediated Cytotoxicity in Multiple Human Cancer Types.
No sample metadata fields
View SamplesMale germ cells express the widest repertoire of transcript variants in mammalian tissues. Nevertheless, factors and mechanisms underlying such pronounced diversity are largely unknown. The splicing regulator Sam68 is highly expressed in meiotic cells and its ablation results in defective spermatogenesis. Herein, we uncover an extensive splicing program operated by Sam68 across meiosis, primarily characterized by alternative last exon (ALE) regulation in genes of functional relevance for spermatogenesis. Lack of Sam68 preferentially causes premature transcript termination at internal polyadenylation sites. Overall design: RNA-Seq data for purified spermatocytes and spermatids isolated from Sam68+/+ and Sam68-/- mice.
Functional Interaction between U1snRNP and Sam68 Insures Proper 3' End Pre-mRNA Processing during Germ Cell Differentiation.
Specimen part, Cell line, Subject
View SamplesThe project had 2 goals:
Pooling samples within microarray studies: a comparative analysis of rat liver transcription response to prototypical toxicants.
No sample metadata fields
View SamplesMus musculus transcriptome during infection with Candida albicans strains SC5314 and 101
Persistence of <i>Candida albicans</i> in the Oral Mucosa Induces a Curbed Inflammatory Host Response That Is Independent of Immunosuppression.
Sex, Specimen part, Cell line
View SamplesWe have used microarrays to identify individual genes and pathways regulated by Gq/11 or G12/13 signalling in type II alveolar epithelial cells isolated from the lungs of knockout mice.
Loss of epithelial Gq and G11 signaling inhibits TGFβ production but promotes IL-33-mediated macrophage polarization and emphysema.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Control of vertebrate multiciliogenesis by miR-449 through direct repression of the Delta/Notch pathway.
Specimen part
View SamplesWe used microarrays to detail the global programme of gene expression that occurs in response to miR-449 or miR-34 overexpression in proliferating HAECs.
Control of vertebrate multiciliogenesis by miR-449 through direct repression of the Delta/Notch pathway.
Specimen part
View SamplesThe regeneration of the airway mucociliary epithelium involves several sequential events including migration, proliferation, polarization and final differentiation (i.e ciliogenesis).
Control of vertebrate multiciliogenesis by miR-449 through direct repression of the Delta/Notch pathway.
Specimen part
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