Alternative processing of pre-mRNA transcripts is a major source of protein diversity in eukaryotes and has been implicated in several disease processes including cancer. In this study we have performed a genome wide analysis of alternative splicing events with the GeneChip Human Exon 1.0 ST Array from Affymetrix in lung adenocarcinoma. We found that ~13.3% of the 17800 core Refseq genes appear to have alternative transcripts that are differentially expressed in lung adenocarcinoma versus normal. According to their known functions the largest subset of these genes (30.8%) is believed to be cancer related. Detailed analysis was performed for several genes using PCR, quantitative RT-PCR and DNA sequencing. We found overexpression of ERG variant 2 but not variant 1 in lung tumors and overexpression of CEACAM1 variant 1 but not variant 2 in lung tumors but not in breast or colon tumors. We also identified a novel, overexpressed variant of CDH3 and verified the overexpression of a novel variant of P16. These findings demonstrate how analysis of alternative pre-mRNA processing can shed additional light on differences between tumors and normal tissues as well as between different tumor types. Such studies may lead to the development of additional tools for tumor diagnosis, prognosis and therapy.
Whole genome exon arrays identify differential expression of alternatively spliced, cancer-related genes in lung cancer.
Sex, Age, Race, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila.
Specimen part, Time
View Samplesgene expression profiles in fly brains between wildtype and miR-34 null flies
The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila.
Specimen part, Time
View Samplesgene expression profiles in fly brains with age
The microRNA miR-34 modulates ageing and neurodegeneration in Drosophila.
Specimen part, Time
View SamplesThe conserved multi-subunit Ccr4-Not complex regulates gene expression in diverse ways. In this work, we characterize the suppression of temperature sensitivity associated with a mutation in the gene encoding the scaffold subunit of the Ccr4-Not complex, NOT1, by the deletion of SPT3.
A SAGA-independent function of SPT3 mediates transcriptional deregulation in a mutant of the Ccr4-not complex in Saccharomyces cerevisiae.
No sample metadata fields
View SamplesWe used microarrays to analyze gene expression changes in liver after treatment of rats with two compounds from drug development (R1, R2) to identify potential effects related to hepatotoxicity.
Gene expression-based in vivo and in vitro prediction of liver toxicity allows compound selection at an early stage of drug development.
Sex, Specimen part, Treatment
View SamplesAcute lung rejection is a risk factor for chronic rejection, jeopardizing the long-term survival of lung transplant recipients. At present, acute rejection is diagnosed by transbronchial lung biopsies, which are invasive, expensive, and subject to significant sampling error. In this study, we sought to identify groups of genes whose collective expression in BAL cells best classifies acute rejection versus no-rejection. BAL samples were analyzed from 32 unique subjects whose concurrent histology showed acute rejection (n=14) or no rejection (n=18). Global BAL cell gene expression was measured using Affymetrix U133A microarrays. The nearest shrunken centroid method with 10-fold cross validation was used to define the classification model. 250 runs of the algorithm were performed to determine the range of misclassification error and the most influential genes in determining classifiers. The estimated overall misclassification rate was below 20%. Seven transcripts were present in every classifier and 52 transcripts were present in at least 70% of classifiers; these transcripts were notable for involvement with T-cell function, cytotoxic CD8 activity, and granulocyte degranulation. The proportions of both lymphocytes and neutrophils in BAL samples increased with increasing probability of acute rejection; this trend was more pronounced with neutrophils. We conclude that there is a prominent acute rejection-associated signature in BAL cells characterized by increased T-cell, CD8+ cytotoxic cell, and neutrophil gene expression; this is consistent with established mechanistic concepts of the acute rejection response.
Bronchoalveolar lavage cell gene expression in acute lung rejection: development of a diagnostic classifier.
No sample metadata fields
View SamplesThe ability to sequence genomes has far outstripped approaches for deciphering the information they encode. Here we present a suite of techniques, based on ribosome profiling (the deep-sequencing of ribosome-protected mRNA fragments), to provide genome-wide maps of protein synthesis as well as a pulse-chase strategy for determining rates of translation elongation. We exploit the propensity of harringtonine to cause ribosomes to accumulate at sites of translation initiation together with a machine learning algorithm to define protein products systematically. Analysis of translation in mouse embryonic stem cells reveals thousands of strong pause sites and novel translation products. These include amino-terminal extensions and truncations and upstream open reading frames with regulatory potential, initiated at both AUG and non-AUG codons, whose translation changes after differentiation. We also define a new class of short, polycistronic ribosome-associated coding RNAs (sprcRNAs) that encode small proteins. Our studies reveal an unanticipated complexity to mammalian proteomes. Overall design: Examination of translation in mouse embryonic stem cells and during differentiation into embryoid bodies
Ribosome profiling provides evidence that large noncoding RNAs do not encode proteins.
Cell line, Treatment, Subject
View SamplesBronchoalveolar lavage samples collected from lung transplant recipients. Numeric portion of sample name is an arbitrary patient ID and AxBx number indicates the perivascular (A) and bronchiolar (B) scores from biopsies collected on the same day as the BAL fluid was collected. Several patients have more than one sample in this series and can be determined by patient number followed by a lower case letter. Acute rejection state is determined by the combined A and B score - specifically, a combined AB score of 2 or greater is considered an acute rejection.
Gene expression profiling of bronchoalveolar lavage cells in acute lung rejection.
No sample metadata fields
View SamplesInfluenza A viruses generate annual epidemics and occasional pandemics of respiratory disease with important consequences for human health and economy. Therefore, a large effort has been devoted to the development of new anti-influenza drugs directed to viral targets, as well as to the identification of cellular targets amenable for anti-influenza therapy. Here we describe a new approach to identify such potential cellular targets by screening collections of drugs approved for human use. We reasoned that this would most probably ensure addressing a cellular target and, if successful, the compound would have a well known pharmacological profile. In addition, we reasoned that a screening using a GFP-based recombinant replicon system would address virus trancription/replication and/or gene expression, and hence address a stage in virus infection more useful for inhibition. By using such strategy we identified Montelukast as an inhibitor of virus gene expression, which reduced virus multiplication in virus-infected cells but did not alter virus RNA synthesis in vitro or viral RNA accumulation in vivo. By deep sequencing of RNA isolated from mock- and virus-infected human cells, treated or not with Montelukast, we identified the PERK-mediated unfolded protein response as the pathway responsible for Montelukast action. Accordingly, PERK phosphorylation was inhibited in infected cells but stimulated in Montelukast-treated cells. These results suggest the PERK-mediated unfolded protein response as a potential cellular target to modulate influenza virus infection. Overall design: Comparison of gene expression measured by deep sequencing (single-ends, 50nt, RNA-seq) of "Infected", "Not infected", "Infected+Montelukast" and "Not infect+Montelukast" in human A549 cells. Infected means "Infected with influenza virus".
Chemical Genomics Identifies the PERK-Mediated Unfolded Protein Stress Response as a Cellular Target for Influenza Virus Inhibition.
No sample metadata fields
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