High-throughput proteomics using submicroliter amounts of plasma for comprehensive assessment of the immune status

使用亚微升血浆进行高通量蛋白质组学综合评估免疫状态

• 批准号: 10287684
• 负责人: Hanno Steen
• 金额: $ 43.44万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-09 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10287684
• 关键词: Acute; Administrative Supplement; Affect; Age-Years; Aging; Alzheimer' s Disease; Amyloid; Biological; Biological Assay; Biological Markers; Blood; Blood Plasma Volume; Blood specimen; COVID-19 pandemic; COVID-19 patient; Charge; Chronically Ill; Clinical Research; Cognition; Cognitive; Collection; Consent; Data; Data Collection; Data Compromising; Data Set; Disease; Elderly; Ensure; Environment; Evaluation; Funding; Grant; Home; Image; Impaired cognition; Inflammation; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Methodology; Methods; Molecular; Nerve Degeneration; Neurobehavioral Manifestations; Neurologic; Neuropsychological Tests; Neuropsychology; Onset of illness; Operations Research; Outcome; Outpatients; Parents; Participant; Pathogenesis; Patients; Phase; Plasma; Positron-Emission Tomography; Proteins; Proteome; Proteomics; Research Personnel; Risk; Sampling; Spottings; Testing; United States National Institutes of Health; Venous; aging population; base; cohort; cytokine; data acquisition; high risk; immunological status; innovation; interest; liquid chromatography mass spectrometry; medical schools; method development; middle age; pandemic disease; participant safety; prospective; sample collection; severe COVID-19; tau Proteins; temporal measurement

Summary The SARS-CoV-2 pandemic of 2020 vastly affected normal clinical and research operations. The negative impact is particularly severe on studies involving older adults given the high risk for severe COVID-19 disease, where the mean/median age of deceased COVID-19 patients is >80 years of age. Due to these unique circumstances, the years `20 and `21 will result in `lost years' for many longitudinal studies that involve older adults as it is too risky for participants to leave the safe environment of their home for e.g. a blood draw. A loss of two years of sampling is particularly damaging for longitudinal studies involving older adults including the NIA-funded BIOCARD Study started in 1995 which has prospectively followed >300 cognitively normal middle-aged participants in an effort to understand the pathogenesis of Alzheimer's disease (AD) and its relationship with aging. This well characterized cohort undergoes detailed annual neuropsychologic testing and blood collection with biannual MRI, PET and CSF collection for understanding the molecular basis of AD. The challenge is to ensure the safety of these subjects without compromising data collection. One possibility is to use NoviPlex cards for the safe at home collection of blood samples. However, only 2.5ul of plasma can be collected – with current proteomics methods, this amount of plasma cannot yield a deep quantitative data set. We hypothesize that integrating at home sample collection strategies using the NoviPlex cards and state-of-the- art sample-sparing analyses strategies being developed by the Steen Lab (U24AI152179: High-throughput proteomics using submicroliter amounts of plasma for comprehensive assessment of the immune status) will allow the safe collection of samples and data from vulnerable patients during the current COVID-19 pandemic. We propose that our platform will facilitate high quality data acquisition on small plasma volumes collected at home in a quick and easy manner. Such an integrated sample-sparing collection and analysis strategy will allow researchers to continue collecting useful plasma samples from participants of the BIOCARD study despite the ongoing COVID-19 pandemic during this critical phase of BIOCARD where a substantive portion of the participants are manifesting cognitive symptoms of AD given their advanced age. To test our hypothesis, we will compare the proteome of venous vs. microcapillary (i.e. NoviPlex card) plasma (Specific Aim 1) and collect microcapillary plasma remotely from active participants in the longitudinal BIOCARD study (Specific Aim 2). This proposal for an administrative supplement will add an AD focus on the existing U24 from Dr. Steen, which currently focuses on sample sparing plasma proteomic assays. The requested supplement will allow us to establish an innovative approach facilitating remote collection of microcapillary plasma and high-quality data in 2021 from high-risk participants of the unique BIOCARD study. Furthermore, this home sampling strategy will enable plasma sample collection with a much higher temporal resolution than currently feasible and financially viable, which is of significant interest for a wide range of longitudinal studies.

概括 2020年的SARS-COV-2大流行极大地影响了正常的临床和研究操作。负面影响 鉴于严重的Covid-19疾病的高风险，在涉及老年人的研究中特别严重，那里 已故Covid-19患者的平均/中位年龄> 80岁。由于这些独特的情况， 对于许多涉及老年人的纵向研究，“ 20岁和21岁”将导致“损失年” 参与者有冒险离开房屋的安全环境，例如抽血。 对于纵向研究涉及老年人，包括 NIA资助的Biocard研究始于1995年，该研究前瞻性地遵循了> 300的认知正常 中年参与者努力了解阿尔茨海默氏病（AD）及其发病机理 与衰老的关系。这个特征性的队列进行了详细的年度神经心理学测试和 收集双年度MRI，PET和CSF收集的血液，以了解AD的分子基础。这 挑战是确保这些受试者的安全性，而无需妥协数据收集。一种可能性是 使用Noviplex卡作为安全收藏的血液样本。但是，只有2.5英寸的等离子体可以是 收集的 - 使用当前的蛋白质组学方法，这种数量的等离子体无法产生深度的定量数据集。 我们假设使用Noviplex卡和最先进的家庭集成样本收集策略 ART样本分析分析Steen Lab开发的策略（U24AI152179：高通量 蛋白质组学使用亚微压数量的血浆数量进行全面评估免疫状态） 在当前的Covid-19大流行期间，允许安全收集来自脆弱患者的样品和数据。 我们建议我们的平台将促进收集的小等离子体量的高质量数据获取 快速简便地回家。这样的集成样本收集和分析策略将允许 研究人员继续从生物卡研究的参与者那里收集有用的等离子体样本。 在生物卡的这个关键阶段，正在进行的共同19-19大流行 鉴于其高龄，参与者表现出AD的认知症状。为了检验我们的假设，我们将 比较静脉与微毛细血管（即诺维普列卡）等离子体（特定目标1）的蛋白质组并收集 纵向生物卡研究中的活跃参与者的微毛细血管血浆（特定目标2）。 该提案的行政补充提案将增加广告的关注Steen博士的现有U24， 目前专注于样品较高的等离子体蛋白质组学测定。请求的补充剂将使我们能够 建立一种创新方法，促进远程微毛细血管等离子体和高质量数据集合 2021年，来自独特的生物卡研究的高风险参与者。此外，这种家庭抽样策略将 启用比目前可行和财务的临时分辨率要高得多的等离子体样本收集 可行的，对于广泛的纵向研究而言，它具有重大兴趣。