Transcriptional profiles of the host response to dengue fever

登革热是地球仪最重要的新发传染病之一。这个目标 该项目的目的是描述登革热儿童的转录反应。各项广泛目标 确定宿主反应的保护性和致病性特征的关键特征，并提供 为开发登革热和其他类似疾病的新型诊断和预后工具奠定了基础 疾病。有三个具体目标： 艾姆岛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本丰度水平 在尼加拉瓜的马那瓜，从被诊断患有登革热的儿童收集的PBMC样品。我们将 评估与基因表达个体间变异相关的临床和实验室特征， 并确定转录谱和WHO分期标准之间的关系。分析 连续样本将提供有关临床相关药物相对稳定性的重要信息， 表达签名，并帮助识别相关生物过程中的时间趋势。 目标2.登革出血热/登革休克预测基因集的鉴定 综合征 区分注定要发展DHF/DSS的儿童与注定要发展DHF/DSS的儿童的能力 良性感染过程是一个关键的未满足的临床需求。我们将确定一组基因， 相应的转录本丰度模式预测急性登革感染的临床演变。一个 这项工作的一个重要特点是使用在一个单独的登革热季节收集的样本， 独立测试集进行验证。 目标3。利用转录谱对登革热和登革热样疾病进行分类。 将在接受登革热评估的患者中测量全基因组转录本丰度 因为临床表现相似，但没有发现登革热。表达的比较 来自那些患有和没有登革热的人的概况将导致识别宿主反应特征， 登革热特异性的，以及那些在许多感染中保守的。这项工作将确定标记， 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.