RNA-seq analysis of 16 B6J x B6NJ-F2 mice which are homozygous for either the wild-type B6J allele (binge-resistant; J/J) or mutant B6NJ allele (binge-prone; N/N), at rs240617401, a marker denoting a missense SNP in Cyfip2. Genotype identity is denoted as either J for binge-resistant; J/J, or N for binge-prone; N/N. Overall design: A sample size of N=8 per genotype was employed (4 females, 4 males; 69-100 days old at the time of sacrifice). Striatum punches were harvested on Day 24 immediately following the 5-min behavioral test on the EPM, stored in RNAlater for 48 h, blotted dry with a kimwipe, and transferred to -80ºC. Total RNA was isolated and shipped to the University of Chicago Genomics Core Facility for cDNA library preparation using the Illumina TruSeq Stranded mRNA LT Sample Prep Kit (50 bp single-end reads). Samples were sequenced using the Illumina HiSeq 4000 with 16 samples per lane over four lanes (technical quadruplicates). FASTQ files were quality checked via FASTQC and all samples exhibited Phred quality scores greater than 30 (i.e. less than 0.1% sequencing error). FASTQ files were used to align reads to the reference genome using TopHat (mm10; UCSC Genome Browser). Read counts per gene were quantified using the HTSeq Python package.
Cytoplasmic FMR1-Interacting Protein 2 Is a Major Genetic Factor Underlying Binge Eating.
Sex, Specimen part, Subject
View SamplesRNA-seq analysis of 8 Cyfip2N/- and 8 Cyfip2N/N mice. Cyfip2N/- are mice contain one copy of the B6NJ missense mutation and one copy of the nonsense mutation (binge-resistant; N/-), whereas Cyfip2N/N are mice that have two mutated B6NJ allele (binge-prone; N/N), at rs240617401, a marker denoting a missense SNP in Cyfip2. Genotype identity is denoted as either J for binge-resistant; N/-, or N for binge-prone; N/N. Overall design: A sample size of N=8 per genotype was employed (4 females, 4 males; 82-84 days old at the time of sacrifice). Striatum punches were harvested on Day 24 immediately following the 5-min behavioral test on the EPM, stored in RNAlater for 48 h, blotted dry with a kimwipe, and transferred to -80ºC. Total RNA was isolated and shipped to the University of Chicago Genomics Core Facility for cDNA library preparation using the Illumina TruSeq Stranded mRNA LT Sample Prep Kit (50 bp single-end reads). Samples were sequenced using the Illumina HiSeq 4000 with 16 samples per lane over four lanes (technical quadruplicates). FASTQ files were quality checked via FASTQC and all samples exhibited Phred quality scores greater than 30 (i.e. less than 0.1% sequencing error). FASTQ files were used to align reads to the reference genome using TopHat (mm10; UCSC Genome Browser). Read counts per gene were quantified using the HTSeq Python package.
Cytoplasmic FMR1-Interacting Protein 2 Is a Major Genetic Factor Underlying Binge Eating.
Sex, Specimen part, Cell line, Subject
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 SamplesAs part of a large genetic evolution study we also acquired 3'UTR expression arrays at two time points for the same 18 patients with CLL.
Evolution and impact of subclonal mutations in chronic lymphocytic leukemia.
Specimen part, Disease, Disease stage, Subject, Time
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
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Comparative epigenomic analysis of murine and human adipogenesis.
Sex, Specimen part
View SamplesHuman abdominal adipose tissue was obtained with informed consent from a 33-year old Caucasian female (BMI = 32.96 Kg/m2) undergoing lipoaspiration. Adipose stromal cells (hASCs) were isolated and differentiated into adipocytes in vitro.
Comparative epigenomic analysis of murine and human adipogenesis.
Sex, Specimen part
View Samples