Core C - Proteomics Core

摘要 在登革热人类免疫学项目联盟的蛋白质组学核心(核心C)中，我们将应用 基于质谱学的蛋白质组学方法定量测量对病毒感染和 在临床队列中接种疫苗。我们将首先测量一些蛋白质读数的全球变化，包括 感染登革病毒的体外原代细胞中的磷酸化、泛素化和蛋白质丰度 在临床样本中确定值得在更有针对性的蛋白质组学研究中追求的感兴趣的蛋白质。数据来自 核心C将通过核心E与核心B(基因组核心)和核心D(免疫监测核心)的数据进行集成 (数据分析和建模核心)选择大约200种蛋白质进行灵敏分析 用于从非常有限的样本量中进行检测和量化。最后，我们将应用所开发的分析方法 量化来自自然人群临床队列的患者来源样本中的蛋白质反应，以进行比较 病毒感染和疫苗接种的临床结果。这些有针对性的蛋白质组学方法也将用于 在干扰预测的宿主驱动基因后进行体外验证研究。

SUMMARY In the Proteomics Core (Core C), part of the Dengue Human Immunology Project Consortium, we will apply mass spectrometry-based proteomics approaches to quantitatively measure responses to viral infection and vaccination in clinical cohorts. We will first measure global changes in a number of protein readouts including phosphorylation, ubiquitination, and protein abundance, in ex vivo primary cells infected with Dengue virus to identify proteins of interest worth pursuing in more targeted proteomics studies in clinical samples. Data from Core C will be integrated with data from Cores B (Genomics Core) and D (Immune Monitoring Core) by Core E (Data Analysis and Modeling Core) to select approximately 200 proteins for which to develop sensitive assays for detection and quantification from very limited sample amounts. Finally, we will apply the developed assays to quantify protein responses in patient-derived samples from clinical cohorts in natural populations to compare clinical outcomes of viral infection and vaccination. These targeted proteomics approach will also be used to conduct ex vivo validation studies after perturbing predicted host driver genes.