Project description:Severe fever with thrombocytopenia syndrome (SFTS) is a new tick-borne infectious disease caused by a new SFTS virus (SFTSV). Due to its 12%-50% high fatality rate and the possibility of pandemic transmission, as well as no specific antiviral drugs for the treatment so far, SFTSV has been listed as one of the top 10 priority infectious diseases by the World Health Organization. Currently, there are rare studies of transcriptomic analysis for the patients infected with SFTSV, which makes it difficult to deeply understand the life cyle and pathogenicity of this virus. To explore the differences of transcripts after SFTSV infection, we performed a longitudinal sampling study to systematically investigate the chronological changes of viral load and transcriptomic and epigenetic characterization using white blood cells from SFTSV patients. The results showed significant changes in the expression of some genes from onset to recovery of SFTSV infection. Moreover, these differentially expressed genes showed good consistency in the three patients at different stages of treatment, which may contribute to the pathophysiology of SFTSV and thus lead to a breakthrough in SFTSV therapy. Moreover, by m6A-seq, we found some genes that might be regulated by m6A. This study in transcript changes and RNA modification may open a brand new direction to our understanding of SFTSV and play an important role in the drugs discovery for effective treatment.
Project description:The Uppsala Longitudinal Study of Adult Men is a population-based study aimed at identifying risk factors for cardiovascular disease. At the time of biopsy all subjects were ~ 70yr of age
Project description:Rationale: Molecular markers of disease progression in idiopathic pulmonary fibrosis are needed. Objective: Derive and validate a blood transcriptomic predictor of forced vital capacity (FVC) decline. Methods: A training cohort (n=74) of IPF patients was stratified according to the presence of progressive disease, defined as ≥10% relative decline in FVC over 12 months. Baseline to 4-month within-patient changes in gene expression were correlated with categorical FVC decline. Genes predictive of FVC decline were identified by two-group comparison with false discovery rate <5% followed by logistic LASSO regression and 10-Fold Cross-Validation for gene list prioritization. Independent validation cohorts with differing transcriptome assay platforms and blood transcriptome sampling times from UChicago (n=27), UPMC (n=35), and Imperial (n=24) underwent receiver operating characteristic with area under the curve (AUC) analyses for validation. Results: A longitudinally-derived FVC-gene predictor accurately discriminated most patients with stable and progressive IPF across four independent IPF cohorts with variable transcriptomic assay platforms and sampling times. The FVC-gene predictorand demonstrated sensitivity and specificity of 74.3% and 82.4% in the combined replication cohort. The likelihood ratio, LR+ and LR- were 4.11 and 0.32, respectively. TGF-beta was the highest-ranking canonical pathway by Gene Set Enrichment Analysis. An approach using longitudinal gene expression changes approach dramatically reduced within-group variation compared to cross-sectional expression for improved prediction modeling. Conclusions: This novel FVC-gene predictor developed from short-term longitudinal gene expression changes successfully discriminates most patients with high likelihood of one-year 10% FVC decline. This tool may better reflect disease activity and prove useful for predictive enrichment of clinical trial populations.