Project description:Simple Markov model for a disease model.
The model uses two disease states: Alive and Dead, where the Dead state terminates simulation.
The yearly probability of transition between states Alive and Dead is: 0.05
Initial conditions: 100 people start in Alive and none in Dead.
Output: Number of people in each state for years 1-10.
Project description:Microarray was performed on PBMC with an inflammatory dedicated slide of 340 genes, and target samples labelled with Cy3 for day 0 (reference) and with Cy5 for the other days. Changes in expression levels were evaluated by the ratio Dx/D0. According to outcome and time evolution, a two-dimensional clustering was performed. Keywords: dead vs alive septic shock patients at D1 post-inclusion
Project description:In the present study we evaluated the miRNA expression profile of 31 high risk, stage 4 neuroblastoma patients. We compared miRNA expression profiles of 14 long-survivors (alive with an overall survival time > 36 months) and 17 short-survivors (dead of disease within 36 months from diagnosis. Deaths due to toxicity were censored).
Project description:Rationale: Serial measurements of genome-wide transcriptional changes in alveolar macrophages (AMs) in patients with acute respiratory distress syndrome (ARDS) could identify dynamic biologic processes that are associated with clinical outcomes. Objectives: To identify associations between AM transcriptional programs and the composite endpoint of ventilator-free days (VFDs) over the course of ARDS. Methods: We performed unbiased genome-wide transcriptional profiling of AMs purified from bronchoalveolar lavage fluid collected from patients with ARDS. Cells were obtained at baseline (Day 1), Day 4, and Day 8 after ARDS onset. We assessed pathway enrichment in subjects with VFDs > 0 (VFD-Extubated/Alive) versus VFDs = 0 (VFD-Intubated/Dead) at each time point. Measurements and Main Results: We found highly divergent AM transcriptional patterns at all time points between ARDS patients based on their VFD status (FDR < 0.05). “M1-like” and pro-inflammatory gene sets such as IL-6-JAK-STAT signaling were significantly enriched in AMs isolated on Day 1 in VFD-Extubated/Alive versus VFD-Intubated/Dead subjects. In contrast, many of these same gene sets were associated with the VFD-Intubated/Dead subjects on Day 8. In patients who had samples from each time point, we identified multiple AM gene clusters whose temporal expression patterns were associated with VFD status. The relationship between AM expression profiles and VFDs was distinct in subjects with Direct (pulmonary) versus Indirect (extrapulmonary) ARDS. Conclusion: Clinically meaningful outcomes over the course of ARDS are associated with highly distinct AM transcriptional programs. Our findings suggest that interventions targeting the alveolar immune response should be tested within strictly defined time periods.
2019-03-31 | GSE116560 | GEO
Project description:RNA-seq for macrophages infected by dead or alive bacterial
Project description:A healthy existence relationship between mussels and environment relies on suitable PH, adequate oxygen and suitable temperature. Besides ocean acidification, ocean warming has been shown to cause mussel dead, a phenomenon responsible for extensive mussel dead around the word. How heat stress impacts mussel alive is poorly understood. We founded that. The superoxide dismutase (SOD) activity of two treatment groups were significantly higher than that of control group, and the activity of acid phosphatase (ACP) was significantly higher in two treatment groups than control group. The lactate dehydrogenase (LDH) activity of 26 ℃ treatment group was significantly higher than that of control group, and the LDH activity of 33 ℃ treatment group was significantly lower than that of control group. Cellular content of lysozyme (LZM) was significantly higher in two treatment groups than control group. In this study, we applied TMT quantification to investigate how Mytilus coruscus responds to heat stress (26 ℃, 33 ℃). We identified 1652 to 1878 differentially expressed proteins (DEPs) from these heat conditions, among which 897 were commonly regulated by all the two temperature and were significantly enriched in nutrients digestion and absorption (e. g. fat digestion and absorption). Furthermore, proteins associated with nutrients metabolism, signaling pathways (p53 signaling pathway and MAPK signaling pathway)and energy metabolism (e. g. TCA cycle) were impacted, suggesting that the ability of basic metabolism of Mytilus coruscus may be altered by heat stress.
Project description:Villin-Cre+ Lsd1fl/fl (cKO) mice display an immature intestinal epithelium characterized by an incomplete differentiation of enterocytes and secretory lineages, reduced number of goblet cells and a complete loss of Paneth cells. This experiment aims to elucidate the differences in stool microbial composition derived from WT (Villin-Cre- Lsd1fl/fl) and cKO mice both in adult (2-month-old) and neonatal (14 days postpartum P14) stages. Different timepoints are crucial to understand the role of intestinal maturation in microbiome composition since said maturation is dependent on time-dependent external cues happening at P14-21 (weaning and transition from milk to solid foods).
Project description:Clinical data from IMblaze370: Clinical data include disease, treatment arm, MSI status, KRAS oncogenic mutation status, sex, and overall survival (1=dead, 0=alive)
Project description:With the technological advances of the last decade, it is now feasible to analyze environmental samples of vast complexity, such as human stool specimen, using meta-omics techniques like metaproteomics. Still the most sophisticated, sensitive instruments can only extract information that a sample contains in the first place. This highlights the need for initial sample preparation to preserve as much unaltered information as possible. Yet little is known about the effects different processing approaches have on the final analysis results. This study analyzes human stool samples applying metaproteomics and shows that the initial sample storage has a massive effect on the taxonomic composition of proteins identified. The findings are backed up by the results of the metagenomics analysis of the same samples. This suggests, that great care should be taken in choosing storage conditions for (omics) studies, as well as in comparing the results of experiments with different initial processing.
Project description:<p>We investigate the hypothesis that consistent changes in the human gut microbiome are associated with Crohn's disease, a form of inflammatory bowel disease, and that altered microbiota contributes to pathogenesis. Analysis of this problem is greatly complicated by the fact that multiple factors influence the composition of the gut microbiota, including diet, host genotype, and disease state. For example, data from us and others document a drastic impact of diet on the composition of the gut microbiome. No amount of sequencing will yield a useful picture of the role of the microbiota in disease if samples are confounded with uncontrolled variables.</p> <p>We aim to characterize the composition of the gut microbiome while controlling for diet, host genotype, and disease state. Diet is controlled by analyzing children treated for Crohn's disease by placing them on a standardized elemental diet, and by testing effects of different diets on the gut microbiome composition in adult volunteers. Genotype is analyzed by large scale SNP genotyping, which is already underway and separately funded--team member Hakon Hakonarson is currently genotyping 50 children a week at ~half a million loci each and investigating connections with inflammatory bowel disease. Clinical status is ascertained in the very large IBD practice in the UPenn/CHOP hospital system. Effects of diet, host genotype, and disease state on the gut microbiome are summarized in a multivariate model, allowing connections between microbiome and disease to be assessed free of confounding factors.</p> <p>This project is divided into four sub-studies. In the Fecal Storage Methods (FSM) study, methods of stool storage and DNA extraction are compared to examine their impact on DNA sequence analysis results. The Controlled Feeding Experiment (CaFE) addresses the effects of controlled diets on the gut microbiome. In the Cross-sectional Study of Diet and Stool Microbiome Composition (COMBO), the effects of diet analyzed using surveys and deep sequencing of stool specimens. The fourth study, Pediatric Longitudinal Study of Elemental Diet and Stool Microbiome Composition (PLEASE), examines the effects of an elemental diet treatment on pediatric patients diagnosed with inflammatory bowel disease (IBD), particularly Crohn's disease.</p> <p> <ul> <li>Fecal Storage Methods (FSM): Cross-sectional study</li> <li>Controlled Feeding Experiment (CaFE): Controlled trial</li> <li>Cross-sectional Study of Diet and Stool Microbiome Composition (COMBO): Cross-sectional study</li> <li>Pediatric Longitudinal Study of Elemental Diet and Stool Microbiome Composition (PLEASE): Longitudinal cohort study</li> </ul> </p>