Proteogenomic studies aimed at understanding ovarian tumor responses to agents targeting the DNA damage response and translating this knowledge into clinical benefit

摘要 我们将为阿尔茨海默病（AD）社区提供一种基于先进的检测资源， 能够精确、高度特异性、可重复、多重定量先天免疫的方法- AD脑组织中补体蛋白网络。先天免疫反应及其与炎症的联系是 对于AD的病理生理学是重要的，并且代表了可行的治疗靶标。调节免疫 系统是数百种蛋白质之间相互作用的结果， 方法（例如，免疫测定）通常一次靶向一种分析物，这不足以研究分析物。 一个复杂而强大的信号网络的行为，如先天免疫。我们将开发多重检测 为了量化先天免疫网络中的蛋白质，使用NextGen蛋白质量化平台， 多反应监测（MRM）是质谱分析的一种靶向形式。所有试验方案和验证 数据将作为一种新的资源，通过已建立的、开放源代码的国家信息基础设施（NCI）向公众开放 分析门户网站（assays.cancer.gov）。我们认为，这项工作可能会刺激更多的工作， 通过为AD社区提供基于先进方法学的新型分析资源， 这使得能够精确、高度特异性、可重复、多重定量炎症/先天性 AD脑内免疫蛋白网络

ABSTRACT We will provide the Alzheimer’s disease (AD) community with a novel assay resource based on advanced methodology that enables precise, highly specific, standardizable, multiplex quantification of the innate immunity- complement protein network in AD brain tissues. The innate immune response and its ties to inflammation are important to the pathophysiology of AD and represents a viable therapeutic target. Regulation of the immune system is the result of interplay amongst many 100s of proteins, and conventional protein quantification approaches (e.g. immunoassays) typically target one analyte at a time, which is not adequate for studying the behavior of a complex and robust signaling network such as innate immunity. We will develop multiplex assays to quantify proteins in the innate immune network, using a NextGen protein quantification platform based on a targeted form of mass spectrometry called multiple reaction monitoring (MRM). All assay protocols and validation data will be made publicly available as a novel resource to the community via the established, open-source NCI Assay Portal (assays.cancer.gov). We believe that this work is likely to stimulate additional work leading to progress on AD by providing the AD community with a novel assay resource based on advanced methodology that enables precise, highly specific, standardizable, multiplex quantification of the inflammation / innate immunity protein network in AD brains.