Threatened preterm labor (TPTL) is defined as persistent premature uterine contractions between 20 and 37 weeks of gestation and is the most common condition that requires hospitalization during pregnancy. Most of these TPTL women continue their pregnancies to term while only an estimated 5% will deliver a premature baby within ten days. The aim of this work was to study differential whole blood gene expression associated with spontaneous preterm birth (sPTB) within 48 hours of hospital admission. Peripheral blood was collected at point of hospital admission from 154 women with TPTL before any medical treatment. Microarrays were utilized to investigate differential whole blood gene expression between TPTL women who did (n = 48) or did not have a sPTB (n = 106) within 48 hours of admission. Total leukocyte and neutrophil counts were significantly higher (35% and 41% respectively) in women who had sPTB than women who did not deliver within 48 hours (p<0.001). Fetal fibronectin (fFN) test was performed on 62 women. There was no difference in the urine, vaginal and placental microbiology and histopathology reports between the two groups of women. There were 469 significant differentially expressed genes (FDR<0.05); 28 differentially expressed genes were chosen for microarray validation using qRT-PCR and 20 out of 28 genes were successfully validated (p<0.05). An optimal random forest classifier model to predict sPTB was achieved using the top nine differentially expressed genes coupled with peripheral clinical blood data (sensitivity 70.8%, specificity 75.5%). These differentially expressed genes may further elucidate the underlying mechanisms of sPTB and pave the way for future systems biology studies to predict sPTB.
Whole blood gene expression profile associated with spontaneous preterm birth in women with threatened preterm labor.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Transcriptional profiles underlying parent-of-origin effects in seeds of Arabidopsis thaliana.
No sample metadata fields
View SamplesCrossing plants of the same species but different ploidies can have dramatic effects on seed growth, but little is known about the alterations to transcriptional programmes responsible for this. Parental genomic imbalance particularly affects proliferation of the endosperm, with an increased ratio of paternally to maternally contributed genomes (paternal excess) associated with overproliferation, while maternal excess inhibits endosperm growth. One interpretation is that interploidy crosses disrupt the balance in the seed of active copies of parentally imprinted genes. This is supported by the observation that mutations in imprinted FIS-class genes of Arabidopsis thaliana share many features of the paternal excess phenotype. Here we investigated gene expression underlying parent-of-origin effects in Arabidopsis through transcriptional profiling of siliques generated by interploidy crosses and FIS-class mutants.
Transcriptional profiles underlying parent-of-origin effects in seeds of Arabidopsis thaliana.
No sample metadata fields
View SamplesTo investigate maternal whole blood gene expression profiles associated with spontaneous preterm birth (SPTB, <37 weeks) in asymptomatic pregnant women.
Maternal Whole Blood Gene Expression at 18 and 28 Weeks of Gestation Associated with Spontaneous Preterm Birth in Asymptomatic Women.
Specimen part, Subject
View SamplesPurpose: The JBR.10 trial demonstrated benefit from adjuvant cisplatin/vinorelbine (ACT) in early-stage non-small-cell lung cancer (NSCLC). We hypothesized that expression profiling may identify stage-independent subgroups who might benefit from ACT.
Prognostic and predictive gene signature for adjuvant chemotherapy in resected non-small-cell lung cancer.
Sex, Age, Specimen part
View SamplesHere we studied the effects of anticonvulsant drug exposure in a human embryonic stem cell (hESC) based neuro- developmental toxicity test (hESTn). During neural differentiation the cells were exposed, for either 1 or 7 days, to non-cytotoxic concentration ranges of valproic acid (VPA) or carbamazepine (CBZ), anti-epileptic drugs known to cause neurodevelopmental toxicity.
Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay.
Time
View SamplesWe performed gene expression profiling of laser capture microdissected normal non-neoplastic prostate (cystoprostatectomies) epithelial tissue and compared it to non-transformed and neoplastic low and high grade prostate epithelial tissue from radical prostatectomies, each with its immediately surrounding stroma.
Stromal and epithelial transcriptional map of initiation progression and metastatic potential of human prostate cancer.
No sample metadata fields
View SamplesLeft ventricular mass (LVM) and cardiac gene expression are complex traits regulated by factors both intrinsic and extrinsic to the heart. To dissect the major determinants of LVM, we combined expression quantitative trait locus1 and quantitative trait transcript (QTT) analyses of the cardiac transcriptome in the rat. Using these methods and in vitro functional assays, we identified osteoglycin (Ogn) as a major candidate regulator of rat LVM, with increased Ogn protein expression associated with elevated LVM. We also applied genome-wide QTT analysis to the human heart and observed that, out of 22,000 transcripts, OGN transcript abundance had the highest correlation with LVM. We further confirmed a role for Ogn in the in vivo regulation of LVM in Ogn knockout mice. Taken together, these data implicate Ogn as a key regulator of LVM in rats, mice and humans, and suggest that Ogn modifies the hypertrophic response to extrinsic factors such as hypertension and aortic stenosis.
Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass.
Sex, Age, Specimen part
View SamplesZebrafish embryos have been proposed as an attractive alternative model system for hepatotoxicity testing.
A transcriptomics-based hepatotoxicity comparison between the zebrafish embryo and established human and rodent in vitro and in vivo models using cyclosporine A, amiodarone and acetaminophen.
Compound
View SamplesThe histone deacetylase HDAC2, which negatively regulates neuronal plasticity and synaptic gene expression, is upregulated both in Alzheimer’s disease (AD) patients and mouse models (Graff et al., 2012). Therapeutics targeting HDAC2 are speculated to be a promising avenue for ameliorating AD related cognitive impairment. However, attempts to generate HDAC2-specific inhibitors have not been successful. Here, we take a novel approach utilizing integrative genomics to identify proteins that mediate HDAC2 recruitment to synaptic plasticity genes. Functional screening revealed that knockdown of the transcription factor Sp3 phenocopied HDAC2 knockdown, and that Sp3 facilitated the recruitment of HDAC2 to synaptic genes. Importantly, like HDAC2, Sp3 expression was elevated in AD patients and mouse models, where Sp3 knockdown ameliorated synaptic dysfunction. Furthermore, exogenous expression of an HDAC2 fragment containing the Sp3 binding domain fully restored synaptic plasticity and memory in a mouse model with severe neurodegeneration. Our findings indicate that targeting the HDAC2-Sp3 complex could enhance synaptic and cognitive function, without affecting HDAC2 function in other processes. Overall design: We profiled gene expression levels in primary neurons treated with HDAC2 or Sp3 shRNAs through RNA-Seq to examine whether HDAC2 and Sp3 cooperatively regulate a set of genes.
The Transcription Factor Sp3 Cooperates with HDAC2 to Regulate Synaptic Function and Plasticity in Neurons.
Specimen part, Treatment, Subject
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