Transcriptional profiles of the host response to dengue fever

登革热是全球最重要的新发传染病之一。这样做的目的是 该项目旨在描述登革热儿童的转录反应。总体目标 是识别寄主反应的保护性和致病性的关键特征，并提供 在登革热和其他类似疾病中开发新的诊断和预后工具的基础 疾病。具体目标有三个： 目的一、转录反应与疾病关系的表征 登革热感染的演变。 将在外周血单核细胞中测量全基因组转录丰度水平 (PBMC)从尼加拉瓜马那瓜被诊断为登革热的儿童采集的样本。我们会 评估与基因表达个体间差异相关的临床和实验室特征， 并确定转录图谱与世卫组织分期标准之间的关系。分析 顺序样本将提供有关临床相关的相对稳定性的重要信息 表情特征，并有助于确定相关生物过程中的时间趋势。 目的2.登革出血热/登革休克预测基因集的鉴定 综合症。 区分注定患有DHF/DSS的儿童和注定患有DHF/DSS的儿童的能力 良性的感染过程是一个关键的未得到满足的临床需求。我们将确定一组基因，这些基因 相应的转录丰度模式预测了急性登革热感染的临床演变。一个 这项工作的重要特点是使用在单独的登革热季节收集的样本作为 用于验证的独立测试集。 目的3.利用转录图谱对登革热和类似登革热疾病进行分类。 将对登革热患者进行全基因组转录丰度的测量 因临床表现相似，但均未发现有登革热。表述的比较 来自登革热患者和非登革热患者的简档将导致识别符合以下条件的宿主反应特征 登革热特有的，以及在许多感染中保守的那些。这项工作将识别出 可用于改善登革热和其他类似登革热的疾病的诊断。

Dengue fever is one of the most important emerging infections across the globe. The goal of this project is to characterize the transcriptional responses of children with dengue fever. The broad objectives are to identify critical features of the protective and pathogenic features of the host response, and to provide a basis for developing novel diagnostic and prognostic tools in humans with dengue fever and other similar illnesses. There are three Specific Aims: Aim i. Characterization of the relationship between transcriptional response and disease evolution in dengue infection. Genome-wide transcript abundance levels will be measured in peripheral blood mononuclear cell (PBMC) samples collected from children diagnosed with dengue fever in Managua, Nicaragua. We will evaluate the clinical and laboratory features associated with inter-individual variation in gene expression, and determine the relationship between transcriptional profiles and WHO staging criteria. Analysis of sequential samples will provide important information about the relative stability of clinically relevant expression signatures, and help to identify temporal trends in associated biological processes. Aim 2. Identification of a gene set for predicting Dengue Hemorrhagic Fever/Dengue Shock Syndrome. The ability to distinguish children destined to develop DHF/DSS from those who are destined to have a benign course of infection is a critical unmet clinical need. We will identify a set of genes whose corresponding transcript abundance pattern predicts the clinical evolution of acute dengue infection. An important feature of this work will be the use of samples collected over a separate dengue season as an independent test set for validation. Aim 3. Classification of dengue fever and dengue-like illnesses using transcription profiles. Genome-wide transcript abundance will be measured in patients who are evaluated for dengue fever because of similarities in clinical presentation, but are found not to have dengue. Comparison of expression profiles from those with and without dengue will lead to the identification of host response features that are dengue-specific, and those that are conserved among many infections. This work will identify markers that can be used to improve the diagnosis of dengue fever and other diseases that mimic dengue.