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.

摘要 2020年的SARS-CoV-2大流行极大地影响了正常的临床和研究活动。负面影响 鉴于严重新冠肺炎疾病的高风险，涉及老年人的研究尤其严重 已故新冠肺炎患者的平均/中位年龄为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来说，年份`20和`21将导致‘失去的年份’。 对于参与者来说，离开家的安全环境去抽血是有风险的。 损失两年的抽样对涉及老年人的纵向研究尤其有害，包括 NIA资助的BIOCARD研究始于1995年，该研究前瞻性地跟踪了&gt；300认知正常 中年参与者努力了解阿尔茨海默病(AD)的发病机制及其 与衰老的关系。这一特征良好的队列接受了详细的年度神经心理测试和 一年两次的MRI、PET和脑脊液采集，以了解AD的分子基础。这个 挑战是在不影响数据收集的情况下确保这些受试者的安全。一种可能性是 使用Noviplex卡在家中的保险箱采集血样。然而，只有2.5微升的血浆可以 收集--用目前的蛋白质组学方法，这一数量的血浆不能产生深入的定量数据集。 我们假设，使用Noviplex卡和最新状态在家中整合样本收集策略 STEEN实验室正在开发的ART样本节约分析策略(U24AI152179：高通量 使用亚微升血浆来综合评估免疫状态的蛋白质组学)将 在当前的新冠肺炎大流行期间，允许安全地收集脆弱患者的样本和数据。 我们建议，我们的平台将促进在以下地点收集的小容量等离子体的高质量数据采集 以快捷、轻松的方式回家。这种节省样本的综合收集和分析战略将使 研究人员继续从BIOCARD研究的参与者那里收集有用的血浆样本，尽管 正在进行的新冠肺炎大流行在生物多样性的这个关键阶段，在那里， 由于年龄较大，参与者表现出AD的认知症状。为了检验我们的假设，我们将 比较静脉和微血管(即NoviPlex卡片)血浆(特定目标1)的蛋白质组并收集 来自BIOCARD纵向研究(特定目标2)积极参与者的远程微毛细管血浆。 这份关于行政补充的提案将增加斯蒂恩博士对现有U24的AD重点，这 目前专注于节省样品的血浆蛋白质组分析。所要求的补充将使我们能够 建立促进远程收集微毛细管血浆和高质量数据的创新方法 2021年来自独特的BIOCARD研究的高风险参与者。此外，这种家庭抽样策略将 能够以比目前可行和经济上更高的时间分辨率采集血浆样本 可行性，这对广泛的纵向研究具有重要意义。