We have determined the whole genome sequence of an individual at high accuracy and performed an integrated analysis of omics profiles over a 1.5 year period that included healthy and two virally infected states. Omics profiling of transcriptomes, proteomes, cytokines, metabolomes and autoantibodyomes from blood components have revealed extensive, dynamic and broad changes in diverse molecular components and biological pathways that occurred during healthy and disease states. Many changes were associated with allele- and edit-specific expression at the RNA and protein levels, which may contribute to personalized responses. Importantly, genomic information was also used to predict medical risks, including Type II Diabetes (T2D), whose onset was observed during the course of our study using standard clinical tests and molecular profiles, and whose disease progression was monitored and subsequently partially managed. Our study demonstrates that longitudinal personal omics profiling can relate genomic information to global functional omics activity for physiological and medical interpretation of healthy and disease states. Overall design: Examination of blood component in 20 different time points over 1.5 years which includes 2 disease state and 18 healty state Related exome studies at: SRX083314 SRX083313 SRX083312 SRX083311
Personal omics profiling reveals dynamic molecular and medical phenotypes.
Specimen part, Disease, Subject
View SamplesThis study identifies a transciptomic myometrial profile associated with dystocia in spontanous nulliparous term labour
Identification of a myometrial molecular profile for dystocic labor.
Sex, Specimen part
View SamplesRNA sequencing data for four cell lines representing different stages during malignant transformation.
Majority of differentially expressed genes are down-regulated during malignant transformation in a four-stage model.
No sample metadata fields
View SamplesInflammation has pleiotropic effects on carcinogenesis and tumor progression. Signaling through the adaptor protein MyD88 promotes carcinogenesis in several chemically induced cancer models. Interestingly, we observed a protective role for MyD88 in the development of AOM/DSS colitis-associated cancer. The inability of Myd88-/- mice to heal ulcers generated upon injury creates an inflammatory environment that increases the frequency of mutations and results in a dramatic increase in adenoma formation and cancer progression. Susceptibility to colitis development and enhanced polyp formation were also observed in Il18-/- mice upon AOM/DSS treatment, suggesting that the phenotype of MyD88 knockouts is in part due to their inability to signal through the IL-18 receptor. This study revealed a previously unknown level of complexity surrounding MyD88 activities downstream of different receptors that differentially impact tissue homeostasis and carcinogenesis.
MyD88-mediated signaling prevents development of adenocarcinomas of the colon: role of interleukin 18.
Specimen part, Disease, Disease stage
View SamplesExtremely premature birth is associated with an increased risk for hypoxic brain injury due to lung immaturity and this results in severe long-term neurodevelopmental impairments. The susceptible cell types in the cerebral cortex at this critical developmental time point and the molecular mechanisms underlying associated gray matter defects in premature infants are not known. Here, we used a human three-dimensional (3D) cellular system to study the effect of changes in oxygen tension on the mid-gestation human cerebral cortex. We identified specific defects in intermediate progenitors, a cortical cell type associated with the expansion of the human cerebral cortex, and show that these are related to the unfolded protein response (UPR) and cell cycle changes. Moreover, we verify these findings in human primary cortical tissue and demonstrate that a modulator of the UPR pathway can prevent the reduction in intermediate progenitors following hypoxia. We anticipate that this human cellular platform will be useful in studying other environmental and genetic factors underlying brain injury in premature infants. We investigated the transcriptional changes associated with exposure to <1% O2 by performing RNA sequencing. Overall design: RNA-seq, 101 bp singlepaired-end reads; minimum of 40 million high quality reads per sample) at 24 and 48 hours (middle and end of <1% O2 for hypoxic condition), as well as after 72 hours of re-oxygenation at 21% O2.
Human 3D cellular model of hypoxic brain injury of prematurity.
Subject, Time
View SamplesCardiac structural changes associated with dilated cardiomyopathy (DCM) include cardiomyocyte hypertrophy and myocardial fibrosis. Connective Tissue Growth Factor (CTGF) has been associated with tissue remodeling and is highly expressed in failing hearts. To test if inhibition of CTGF would alter the course of cardiac remodeling and preserve cardiac function in the protein kinase C (PKC) mouse model of DCM. Transgenic mice expressing constitutively active PKC in cardiomyocytes develop cardiac dysfunction that was evident by 3 months of age, and that progressed to heart failure, cardiac fibrosis, and increased mortality. Beginning at 3 months of age, mice were treated with an antibody to CTGF (FG-3149) or non-immune IgG control antibody for an additional 3 months. CTGF inhibition significantly improved left ventricular (LV) systolic and diastolic function in PKC mice, and slowed the progression of LV dilatation. Using gene arrays and quantitative PCR, the expression of many genes associated with tissue remodeling were elevated in PKC mice, but significantly decreased by CTGF inhibition, however total collagen deposition was not attenuated. The observation of significantly improved LV function by CTGF inhibition in PKC mice suggests that CTGF inhibition may benefit patients with DCM.
Connective tissue growth factor regulates cardiac function and tissue remodeling in a mouse model of dilated cardiomyopathy.
Sex, Specimen part, Treatment
View SamplesThis file contains gene microarray data from FACS purified mouse high endothelial cells and capillary endothelial cells from peripheral lymph nodes, mesenteric lymph nodes, and Peyers patches. The data will allow for better understanding of the specialization of high endothelial venules (HEV) and their role in lymphocyte recruitment from the blood; the tissue-specific differentiation of lymphoid tissue vasculature; and the specialized features of capillary vs. post-capillary endothelium, including differences in signaling pathways, adhesive properties and mechanisms of hemostasis.
Transcriptional programs of lymphoid tissue capillary and high endothelium reveal control mechanisms for lymphocyte homing.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Homer1a is a core brain molecular correlate of sleep loss.
No sample metadata fields
View SamplesThese studies adress differential changes in gene expression between sleep deprived and control mice. We profiled gene expression at four time points across the 24H Light/Dark cycle to take into account circadian influences and used three different inbred strains to understand the influence of genetic background.
Homer1a is a core brain molecular correlate of sleep loss.
No sample metadata fields
View SamplesThese studies adress differential changes in gene expression between 6h sleep deprived and control mice in the brain and the liver. We profiled gene expression in three different inbred strains to understand the influence of genetic background.
Homer1a is a core brain molecular correlate of sleep loss.
No sample metadata fields
View Samples