Advancing Proteomic Analysis of CSF in Nervous System Diseases

推进神经系统疾病脑脊液的蛋白质组学分析

• 批准号: 8038538
• 负责人: Howard Schulman
• 金额: $ 96.02万
• 依托单位: CAPRION PROTEOMICS USA, LLC
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8038538
• 关键词: Proteomics; nervous system disorder

DESCRIPTION (provided by applicant): Biomarkers for diseases of the nervous system can benefit from advanced proteomic analysis of cerebral spinal fluid (CSF) but some basic biological and pre-analytical parameters of CSF collection and handling, and reproducibility and accuracy of proteomic bioanalysis must first be systematically evaluated. Label-free differential expression profiling involves separation of tryptic digests of the CSF proteome depleted of the most abundant proteins by cation exchange chromatography followed by liquid chromatography coupled online with mass spectrometry. The effect of time from lumbar puncture to freezing at different temperatures with variable blood contamination, freeze thaw cycles, circadian time of collection and other variables will be investigated. The project will generate best practices for future collections and develop a CSF Integrity test for stored samples. Best practices will be applied to biomarker discovery in three pilot case-control studies-frontotemporal lobar degeneration (FTLD), Alzheimer's disease (AD), and schizophrenia, to find new biomarkers and inform power calculations and platforms for future studies. A resource for the neuroscience community will be established with an annotated in-depth catalog of the CSF proteome and research tools to access information about CSF proteins. Finally, the catalog will include information on tryptic peptide for each proteins that will enable academic and pharma investigators to construct a panel of peptides for multiplexed measurements of CSF proteins of choice without the need for antibody by multiple reaction monitoring (MRM), and thereby promote and facilitate biomarker discovery in many diseases of the nervous system. PUBLIC HEALTH RELEVANCE: Biomarkers for diseases of the nervous system can benefit from advanced proteomic analysis of cerebral spinal fluid (CSF) but some basic biological and analytical parameters of CSF collection, handling, and analysis must first be systematically evaluated. The project will generate best practices for future collections and develop a CSF Integrity test for stored samples. Elaboration of an annotated CSF proteome and biomarker discovery in frontotemporal lobar degeneration (FTLD), Alzheimer's disease, and schizophrenia will accelerate biomarker discovery to speed therapeutic development for these major diseases.

描述（由申请人提供）：神经系统疾病的生物标志物可以受益于脑脊髓液（CSF）的先进蛋白质组学分析（CSF），但是CSF收集和处理的某些基本的生物学和预分析参数，以及蛋白质组学生物分析的可重复性和准确性必须首先评估。无标签的差分表达谱分析涉及分离阳离子交换色谱法耗尽最丰富蛋白质的CSF蛋白质组的胰蛋白酶消化，然后是液相色谱法与质谱法耦合。 从腰椎穿刺到在不同温度下冻结的时间的影响，将研究有变化的血液污染，冻结周期，昼夜节律收集时间和其他变量。该项目将为未来的收藏生成最佳实践，并为存储样本开发CSF完整性测试。最佳实践将适用于三个试验病例对照研究 - 乘量宽LOBAR变性（FTLD），阿尔茨海默氏病（AD）和精神分裂症的生物标志物发现，以找到新的生物标志物，并为未来研究提供信息，并告知电源计算和平台。将通过注释的CSF蛋白质组和研究工具来访问有关CSF蛋白质的信息，建立神经科学社区的资源。最后，该目录将包括每种蛋白质的胰蛋白酶肽的信息，这将使学术和制药研究人员能够构建一组肽，以进行选择的CSF蛋白的多重测量，而无需通过多个反应监测（MRM）进行抗体，从而促进和促进和促进许多生物标志性发现的生物标志性发现。 公共卫生相关性：神经系统疾病的生物标志物可以受益于脑脊髓液（CSF）的先进蛋白质组学分析，但是首先必须系统地评估CSF收集，处理和分析的一些基本的生物学和分析参数。该项目将为未来的收藏生成最佳实践，并为存储样本开发CSF完整性测试。 在额颞Lobar变性（FTLD），阿尔茨海默氏病和精神分裂症中阐述带有注释的CSF蛋白质组和生物标志物发现，将加速生物标志物发现这些主要疾病的治疗性发育。