We decompose the genome-wide expression patterns in 38 embryonic human lung (53-154 days post conception/dpc) into their independent, dominant directions of transcriptomic sample variation in order togain global insight of the developing human lung transcriptome.The characteristic genes and their corresponding bioontologic attribute profile for the latter were identified. We noted the overrepresentation of lung specific attributes (e.g., surfactant proteins) traditionally associated with later developmental stages, and highly ranked attributes (e.g., chemokineimmunologic processes) not previously reported nor immediately apparent in an early lung development context. We defined the 3,223gene union of the characteristic genes of the 3 most dominant sources of variation as the developing lung characteristic subtranscriptome (DLCS). It may be regarded as the minimal gene set describing the essential biology of this process. The developing lung series in this transcriptomic variation perspectiveform a contiguous trajectory with critical time points that both correlate with the 2 traditional morphologic stages overlapping -154 dpc and suggest the existence of 2 novel phases within the pseudoglandular stage. To demonstrate that this characterization is robust, we showed that the model could be used to estimate the gestational age of independent human lung tissue samples with a median absolute error of 5 days, based on the DLCS of their lung profile alone. Repeating this procedure on the homologous transcriptome profiles of developing mouse lung 1419 dpc, we were able to recover their correct developmental chronology.
Transcriptomic analysis of human lung development.
Sex, Disease, Race
View SamplesWhole human fetal lung transcriptome profiles from estimated gestational ages 54 to 137 days post conception. Maternal cigarette smoking status is indicated by cotinine levels measured in the corresponding placenta.
Age, Sexual Dimorphism, and Disease Associations in the Developing Human Fetal Lung Transcriptome.
Sex, Specimen part, Subject
View SamplesWT,WTR,MU and MUR replicates from Affymetrix GeneChip Mouse Expression Set 430 Arrays A and B
The octamer binding transcription factor Oct-1 is a stress sensor.
No sample metadata fields
View SamplesRationale: Asthma is a chronic inflammatory airway disease. Children with severe asthma have lower levels of vitamin D than children with moderate asthma, and among children with severe asthma, airway smooth muscle (ASM) mass is inversely related to vitamin D levels. Beta2 agonists are a common asthma medication that act partly by targetting the ASM. We used RNA-Seq to characterize the human ASM transcriptome of fatal and asthma vs. contols at baseline and under two treatment conditions. Methods: The Illumina TruSeq assay was used to prepare 75bp paired-end libraries for ASM cells from white donors, 6 with fatal asthma and 12 control donors under three treatment conditions: 1) no treatment; 2) treatment with a ß2-agonist (i.e. Albuterol, 1µM for 18h); 3) treatment with vitamin D 100 nM for 18h). Llibraries were sequenced with an Illumina Hi-Seq 2000 instrument. The Tuxedo Suite Tools were used to align reads to the hg19 reference genome, assemble transcripts, and perform differential expression analysis using the protocol described in https://github.com/blancahimes/taffeta Overall design: mRNA profiles obtained via RNA-Seq for primary human airway smooth muscle cell lines from fatal asthma or control donors that were treated with vitamin D, albuterol, or were left untreated.
Vitamin D Modulates Expression of the Airway Smooth Muscle Transcriptome in Fatal Asthma.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Global analysis of the impact of environmental perturbation on cis-regulation of gene expression.
Sex, Specimen part, Time
View SamplesGenetic variants altering cis-regulation of normal gene expression (cis-eQTLs) have been extensively mapped in human cells and tissues, but the extent to which environmental perturbation influences such traits has not been studied to date. We carried out large-scale induction experiments using primary human bone cells derived from 113 unrelated donors of Swedish origin harvested under 18 different conditions (seven treatments, two vehicles, each assessed at two time points). The treatments with the largest impact on the transcriptome, verified on two independent expression arrays, included BMP-2 (t=2h), dexamethasone (DEX) (t=24h), and PGE2 (t=24h). Using these treatments, we performed expression profiling for 18,144 RefSeq transcripts applying biological replicates of the complete study cohort (ntotal=782) and combined it with genome-wide SNP-genotyping data in order to map treatment-specific cis-eQTLs. We found that 93% of cis-eQTLs at 1% FDR were replicated in at least one additional treatment and in fact, on average only 1.4% of the cis-eQTLs were considered as treatment-specific at high confidence. The relative invariability of cis-regulation following perturbation was reiterated independently by genome-wide allelic expression tests where only a small proportion of variance could be attributed to treatment, though treatment-specific cis-regulatory effects were 2-6-fold more abundant among up-or downregulated genes. We further followed-up and validated the DEX-specific cis-regulation of the MYO6 and TNC loci and found top cis-regulatory variants located 180 and 250kb upstream of the transcription start sites, respectively. Our results suggest that, as opposed to tissue-specificity of cis-eQTLs, the interaction between cellular environment and cis-variants are relatively rare (~1.5%), but that detection of such specific interactions can be achieved by combination of functional genomic tools.
Global analysis of the impact of environmental perturbation on cis-regulation of gene expression.
Sex, Specimen part, Time
View SamplesGenetic variants altering cis-regulation of normal gene expression (cis-eQTLs) have been extensively mapped in human cells and tissues, but the extent to which environmental perturbation influences such traits has not been studied to date. We carried out large-scale induction experiments using primary human bone cells derived from 113 unrelated donors of Swedish origin harvested under 18 different conditions (seven treatments, two vehicles, each assessed at two time points). The treatments with the largest impact on the transcriptome, verified on two independent expression arrays, included BMP-2 (t=2h), dexamethasone (DEX) (t=24h), and PGE2 (t=24h). Using these treatments, we performed expression profiling for 18,144 RefSeq transcripts applying biological replicates of the complete study cohort (ntotal=782) and combined it with genome-wide SNP-genotyping data in order to map treatment-specific cis-eQTLs. We found that 93% of cis-eQTLs at 1% FDR were replicated in at least one additional treatment and in fact, on average only 1.4% of the cis-eQTLs were considered as treatment-specific at high confidence. The relative invariability of cis-regulation following perturbation was reiterated independently by genome-wide allelic expression tests where only a small proportion of variance could be attributed to treatment, though treatment-specific cis-regulatory effects were 2-6-fold more abundant among up-or downregulated genes. We further followed-up and validated the DEX-specific cis-regulation of the MYO6 and TNC loci and found top cis-regulatory variants located 180 and 250kb upstream of the transcription start sites, respectively. Our results suggest that, as opposed to tissue-specificity of cis-eQTLs, the interaction between cellular environment and cis-variants are relatively rare (~1.5%), but that detection of such specific interactions can be achieved by combination of functional genomic tools.
Global analysis of the impact of environmental perturbation on cis-regulation of gene expression.
Sex, Specimen part, Time
View SamplesGenetic variants altering cis-regulation of normal gene expression (cis-eQTLs) have been extensively mapped in human cells and tissues, but the extent to which environmental perturbation influences such traits has not been studied to date. We carried out large-scale induction experiments using primary human bone cells derived from 113 unrelated donors of Swedish origin harvested under 18 different conditions (seven treatments, two vehicles, each assessed at two time points). The treatments with the largest impact on the transcriptome, verified on two independent expression arrays, included BMP-2 (t=2h), dexamethasone (DEX) (t=24h), and PGE2 (t=24h). Using these treatments, we performed expression profiling for 18,144 RefSeq transcripts applying biological replicates of the complete study cohort (ntotal=782) and combined it with genome-wide SNP-genotyping data in order to map treatment-specific cis-eQTLs. We found that 93% of cis-eQTLs at 1% FDR were replicated in at least one additional treatment and in fact, on average only 1.4% of the cis-eQTLs were considered as treatment-specific at high confidence. The relative invariability of cis-regulation following perturbation was reiterated independently by genome-wide allelic expression tests where only a small proportion of variance could be attributed to treatment, though treatment-specific cis-regulatory effects were 2-6-fold more abundant among up-or downregulated genes. We further followed-up and validated the DEX-specific cis-regulation of the MYO6 and TNC loci and found top cis-regulatory variants located 180 and 250kb upstream of the transcription start sites, respectively. Our results suggest that, as opposed to tissue-specificity of cis-eQTLs, the interaction between cellular environment and cis-variants are relatively rare (~1.5%), but that detection of such specific interactions can be achieved by combination of functional genomic tools.
Global analysis of the impact of environmental perturbation on cis-regulation of gene expression.
Sex, Specimen part, Time
View SamplesGenetic variants altering cis-regulation of normal gene expression (cis-eQTLs) have been extensively mapped in human cells and tissues, but the extent to which environmental perturbation influences such traits has not been studied to date. We carried out large-scale induction experiments using primary human bone cells derived from 113 unrelated donors of Swedish origin harvested under 18 different conditions (seven treatments, two vehicles, each assessed at two time points). The treatments with the largest impact on the transcriptome, verified on two independent expression arrays, included BMP-2 (t=2h), dexamethasone (DEX) (t=24h), and PGE2 (t=24h). Using these treatments, we performed expression profiling for 18,144 RefSeq transcripts applying biological replicates of the complete study cohort (ntotal=782) and combined it with genome-wide SNP-genotyping data in order to map treatment-specific cis-eQTLs. We found that 93% of cis-eQTLs at 1% FDR were replicated in at least one additional treatment and in fact, on average only 1.4% of the cis-eQTLs were considered as treatment-specific at high confidence. The relative invariability of cis-regulation following perturbation was reiterated independently by genome-wide allelic expression tests where only a small proportion of variance could be attributed to treatment, though treatment-specific cis-regulatory effects were 2-6-fold more abundant among up-or downregulated genes. We further followed-up and validated the DEX-specific cis-regulation of the MYO6 and TNC loci and found top cis-regulatory variants located 180 and 250kb upstream of the transcription start sites, respectively. Our results suggest that, as opposed to tissue-specificity of cis-eQTLs, the interaction between cellular environment and cis-variants are relatively rare (~1.5%), but that detection of such specific interactions can be achieved by combination of functional genomic tools.
Global analysis of the impact of environmental perturbation on cis-regulation of gene expression.
Sex, Specimen part, Time
View SamplesFibroadenomas are the most common benign breast tumors in women under 30. Unlike their malignant counterparts, relatively molecular profiling has been done on fibroadenomas. Here we performed gene expression profiling on ten fibroadenomas in order to better characterize these tumors. Through targeted amplicon sequencing, we have found that six of these tumors have MED12 mutations. We show that the MED12 mutations, among others, are associated with activated estrogen signaling, as well as increased invasiveness through upregulation of ECM remodelling genes.
Exome sequencing identifies highly recurrent MED12 somatic mutations in breast fibroadenoma.
Age
View Samples