This SuperSeries is composed of the SubSeries listed below.
No associated publication
Sex, Age, Treatment, Race
View SamplesBiologic agents active in other autoimmune settings have had variable effectiveness in newly diagnosed type 1 diabetes (T1D) where treatment across therapeutic targets is accompanied by transient stabilization of C-peptide levels in some patients, followed by progression at the same rate as in control groups. Why disparate treatments lead to similar clinical courses is currently unknown. Here, we use integrated systems biology and flow cytometry approaches to elucidate immunologic mechanisms associated with C-peptide stabilization in T1D subjects treated with the anti-CD3 monoclonal antibody, teplizumab.
No associated publication
Sex, Age, Treatment, Race
View SamplesAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive weakness from loss of motor neurons. The fundamental pathogenic mechanisms are unknown and recent evidence is implicating a significant role for abnormal exon splicing and RNA processing. Using new comprehensive genomic technologies, we studied exon splicing directly in 12 sporadic ALS and 10 control lumbar spinal cords acquired by a rapid autopsy system that processed nervous systems specifically for genomic studies. ALS patients had rostral onset and caudally advancing disease and abundant residual motor neurons in this region. We created two RNA pools, one from motor neurons collected by laser capture microdissection and one from the surrounding anterior horns. From each, we isolated RNA, amplified mRNA, profiled whole-genome exon splicing, and applied advanced bioinformatics. We employed rigorous quality control measures at all steps and validated findings by qPCR. In the motor neuron enriched mRNA pool, we found two distinct cohorts of mRNA signals, most of which were up-regulated: 148 differentially expressed genes (p103) and 411 aberrantly spliced genes (p105). The aberrantly spliced genes were highly enriched in cell adhesion (p1057), especially cell-matrix as opposed to cell-cell adhesion. Most of the enriching genes encode transmembrane or secreted as opposed to nuclear or cytoplasmic proteins. The differentially expressed genes were not biologically enriched. In the anterior horn enriched mRNA pool, we could not clearly identify mRNA signals or biological enrichment. These findings, perturbed and up-regulated cell-matrix adhesion, suggest possible mechanisms for the contiguously progressive nature of motor neuron degeneration.
Sporadic ALS has compartment-specific aberrant exon splicing and altered cell-matrix adhesion biology.
Sex, Age, Specimen part
View SamplesThe objective of this study was to examine relationships between weight loss through changes in lifestyle and peripheral blood gene expression profiles. Substantial weight loss (-15.2+3.8%) in lifestyle participants was associated with improvement in selected cardiovascular risk factors and significant changes in peripheral blood gene expression from pre- to post-intervention: 132 unique genes showed significant expression changes related to immune function and inflammatory responses involving endothelial activation.
Importance of substantial weight loss for altering gene expression during cardiovascular lifestyle modification.
Sex, Age, Specimen part
View SamplesBackground: Obesity is a risk factor for breast cancer in postmenopausal women and is associated with decreased survival and less favorable clinical characteristics such as greater tumor burden, higher grade, and poor prognosis, regardless of menopausal status. Despite the negative impact of obesity on clinical outcome, molecular mechanisms through which excess adiposity influences breast cancer etiology are not well-defined.
Effect of obesity on molecular characteristics of invasive breast tumors: gene expression analysis in a large cohort of female patients.
Disease stage
View SamplesIntensive lifestyle modification is believed to mediate cardiovascular disease (CVD) risk through traditional pathways that affect endothelial function and progression of atherosclerosis; however, the extent, persistence, and clinical significance of molecular change during lifestyle modification are not well known. Our study reveals that gene expression signatures are significantly modulated by rigorous lifestyle behaviors and track with CVD risk profiles over time.
Intensive cardiovascular risk reduction induces sustainable changes in expression of genes and pathways important to vascular function.
Sex, Age
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Master regulators of FGFR2 signalling and breast cancer risk.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency.
Specimen part, Disease, Disease stage, Subject, Time
View SamplesGenome-wide association studies for breast cancer have identified over 80 different risk regions in the genome, with the FGFR2 locus consistently identified as the most strongly associated locus. However, we know little about the mechanisms by which the FGFR2 locus mediates risk or the pathways in which multiple risk loci may combine to cause disease. Here we use a systems biology approach to elucidate the regulatory networks operating in breast cancer and examine the role of FGFR2 in mediating risk. Using model systems we identify FGFR2-regulated genes and, combining variant set enrichment and eQTL analysis, show that these are preferentially linked to breast cancer risk loci. Our results support the concept that cancer-risk associated genes cluster in pathways
Master regulators of FGFR2 signalling and breast cancer risk.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Dynamics of oscillatory phenotypes in Saccharomyces cerevisiae reveal a network of genome-wide transcriptional oscillators.
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