Project description:Since the emergence of the first cases in Wuhan, China, the novel coronavirus (2019-nCoV) infection has been quickly spreading out to other provinces and neighboring countries. Estimation of the basic reproduction number by means of mathematical modeling can be helpful for determining the potential and severity of an outbreak and providing critical information for identifying the type of disease interventions and intensity. A deterministic compartmental model was devised based on the clinical progression of the disease, epidemiological status of the individuals, and intervention measures. The estimations based on likelihood and model analysis show that the control reproduction number may be as high as 6.47 (95% CI 5.71–7.23). Sensitivity analyses show that interventions, such as intensive contact tracing followed by quarantine and isolation, can effectively reduce the control reproduction number and transmission risk, with the effect of travel restriction adopted by Wuhan on 2019-nCoV infection in Beijing being almost equivalent to increasing quarantine by a 100 thousand baseline value. It is essential to assess how the expensive, resource-intensive measures implemented by the Chinese authorities can contribute to the prevention and control of the 2019-nCoV infection, and how long they should be maintained. Under the most restrictive measures, the outbreak is expected to peak within two weeks (since 23 January 2020) with a significant low peak value. With travel restriction (no imported exposed individuals to Beijing), the number of infected individuals in seven days will decrease by 91.14% in Beijing, compared with the scenario of no travel restriction.
2024-09-02 | BIOMD0000000971 | BioModels
Project description:RNA sequencing of 100 individuals of Batrachium bungei
Project description:Goal was to compare if there were gene expression difference at baseline, without treatment, in the neutrophils of individuals with benign neutropenia vs individuals with normal neutrophil counts
Project description:Immune responses are tightly regulated, yet highly variable between individuals. To investigate human population variation of trained immunity, we immunized healthy individuals with Bacillus Calmette-Guérin (BCG). This live attenuated vaccine induces not only an adaptive immune response against tuberculosis, but also triggers innate immune activation and memory. We established personal immune profiles and chromatin accessibility maps over a time course of BCG vaccination in 323 individuals. This large resource uncovered genetic and epigenetic predictors of baseline immunity and BCG vaccine response. We found that BCG vaccination enhances the innate immune response only in individuals with dormant immune states at baseline, suggesting that exogeneous induction of trained immunity is not a universal booster of innate immunity, but specifically elevates weak innate immune responses. This study advances our understanding of BCG’s heterologous immune-stimulatory effects and trained immunity in humans. Moreover, our results highlight the value of epigenetic cell states as an “endophenotype” that connects immune function with genotype and the environment.
Project description:The study objective was to propose molecular mechanisms of action of the histone deacetylase inhibitor vorinostat. In the PRAVO phase 1 study, patients that were scheduled to receive pelvic palliative radiation to 30 Gy in 3-Gy fractions for gastrointestinal carcinoma, were enrolled onto four sequential dose levels of vorinostat, starting at 100 mg daily with dose escalation in increments of 100 mg. Endpoints included treatment safety and tolerability, tumor response, and biological activity of vorinostat. For the purpose of identifying biomarkers of vorinostat action, peripheral blood mononuclear cells, representing normal tissue exposed to vorinostat, were used. The samples were collected, one at baseline and two on-treatment samples. The time points for sample collection were chosen based on our previous data from experimental colorectal carcinoma models exposed to vorinostat, demonstrating that the maximum tumor histone acetylation 2-3 hours after drug exposure was restored to baseline after 24 hours. In PRAVO study patients, tumor histone hyperacetylation was observed 3 hours after vorinostat administration. From the 17 patients enrolled onto the PRAVO study, a full set of three samples was obtained from 14 individuals: one baseline sample collected prior to commencement of vorinostat treatment (T0), and two on-treatment samples collected 2 and 24 hours after the patient had received the preceding daily dose of vorinostat (T2 and T24). Individual vorinostat dose levels were 100 mg (D100), 200 mg (D200), 300 mg (D300), or 400 mg (D400).
Project description:The host response to COVID-19 pathophysiology over the first days of infection remains largely unclear especially the mechanisms in the blood compartment. We report here on a longitudinal proteomic analysis of acute phase COVID-19 patients, for which we used blood plasma and MRM proteomics with internal standards as well as DIA. We measured samples on admission for 49 patients, of which 21 with additional samples on days 2, 4, 7, and 14 after admission. We also measured 30 externally obtained samples from healthy individuals for comparison at baseline.
Project description:A major goal of systems biology is the development of models that accurately predict responses of a cell or organism to perturbation. Constructing such models requires collection of dense measurements of system states, yet transformation of the data into predictive constructs remains a challenge. As a first step towards modeling human immunity, we have analyzed immune parameters in depth both at baseline and in response to perturbation with influenza vaccination. Peripheral blood cell transcriptomes, serum titers, frequencies of 126 cell subpopulations, and B cell responses were assessed before and after vaccination in 63 individuals and used to develop a systematic, computational framework to dissect inter- and intra-individual variation and build predictive models of post-vaccination antibody responses. Strikingly, independent of age and pre-existing antibody titers, accurate models could be constructed using pre-perturbation parameters alone, which were validated using data from independent baseline time-points. Most of the parameters contributing to prediction delineated temporally-stable baseline differences across individuals, raising the prospect of immune responsiveness prediction before intervention. According to CHI protocol 09-H1-0239, PBMC samples from 63 healthy voluntiers were collected 7 days prior to vaccination, immediately before vaccination (day0), and at 3 time points (day1, day7 and day70) post vaccination. The CHI Consortium
Project description:Analysis of gene expression associated with exercise response. The hypothesis tested was that individuals with Type 2 Diabetes that failed to demonstrate exercise-induced metabolic improvements would also reflect this lack of response in their skeletal muscle transcriptional profile at baseline. Of 186 genes identified by microarray analysis, 70% were upregulated in Responders and downregulated in Non-responders. Several genes involved in substrate metabolism and mitochondrial biogenesis differed significantly between the groups at baseline. This differential baseline gene expression indicated that Non-responders had blunted oxidative capacity. Total RNA extracted from baseline samples of skeletal muscle of obese individuals with Type 2 Diabetes who were characterized as either Responders or Non-responders was examined for differential expression of exercise response-assocated genes.