Project description:Normalized Gene expression data used for meta-analysis from studies: GSE31747, GSE8317, GSE24943, GSE24125. We studied the changes in macaque and human peripheral blood cell gene expression after infection with Ebola Zaire virus (EBZ) to identify host responses that occur before the emergence of symptoms. We integrated data from in vivo and in vitro infection studies of macaque or human peripheral blood. We identified mRNAs that were differentially expressed at early, middle, and late times after infection. The EBZ early genes showing increased or decreased expression were then compared to literature-derived host responses to malaria, rhinovirus and influenza virus which identified the patterns unique to each pathogen. From the group of EBZ-specific genes, we next predicted those that encoded secreted or membrane-associated proteins. Pairs of these host response mRNAs or proteins could become candidates for differential diagnosis of an early EBZ infection, before the emergence of conventional symptoms. Four key immune response pathways that were activated early showed profoundly decreased expression at late times.
Project description:Analysis of neutrophils purified from peripheral blood of patients with symptomatic and pre-symptomatic type 1 diabetes (T1D), at risk of T1D, and healthy controls.
Project description:Immune patterns in Ebola patients were characterized depending on the outcome of the illness. Non-healthy controls were compared to Ebola patients to define the specificity of the immune response against Ebola virus infection.
Project description:Due to an increasingly aging population, the incidence of dementias such as Alzheimer’s disease are steadily rising, with recent estimates predicting >115million dementia sufferers by 2050. The ability to identify early markers in blood, which appear before the onset of clinical symptoms is of considerable interest to allow early intervention, particularly in “high risk” groups such as those with Type 2 Diabetes (T2D). Here we present longitudinal genome-wide DNA methylation data comparing 18 elderly individuals with T2D who developed pre-symptomatic dementia within an 18 month period following baseline assessment to 18 age, sex and education matched controls who maintained normal cognitive function. We identified a highly significant overlap in the effect size of the top-ranked methylation sites at baseline and follow-up, and identified 8 robust loci, some of which have been previously related to neurodegenerative processes, which were consistently differentially methylated prior to symptoms at baseline, and at 18 month follow up, when a diagnosis of pre-symptomatic dementia had been provided. Finally we show a significant overlap in the effect size of the top-ranked methylation sites in converters, only after they develop symptoms of pre-symptomatic dementia, with changes at the same loci in blood samples from patients with clinically-diagnosed Alzheimer’s disease.
Project description:The 2013-2016 Ebola Zaire virus (EBV) outbreak in West Africa resulted in over 28,000 cases and 11,000 deaths. Ebola virus disease (EVD) is a highly virulent systemic disease with a high case fatality rate of ~ 50%. EVD results in hemorrhagic fever marked by an exaggerated systemic inflammatory response, and impaired vascular and coagulation systems. The immune response of patients who either survived or died is characterized by strong differences. Notably, fatalities showed a diminished capacity to mount an appropriate immune response, resulting in high viremia and increased pro-inflammatory cytokine production. In this study, we analyzed 38 sequential samples collected from 12 patients: 8 survivors and 4 fatalities. Our analytical strategy combined three protein-based platforms covering three different fractions of the plasma proteome: the undepleted classical plasma proteome, the depleted plasma proteome, and cytokines/chemokines, using LC/MS- and antibody-based assays, resulting in over 1000 quantified host and pathogen proteins. For depletion of the most abundant plasma proteins, we advanced a perchloric acid-based precipitation method. This method is low cost, high-throughput and robust.