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

基本信息

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
项目类别：
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&apos 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

项目摘要

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运作。鉴于患有严重 COVID-19 疾病的高风险，对涉及老年人的研究尤其严重，其中由于这些独特的情况，死亡的 COVID-19 患者的平均/中位年龄 >80 岁。对于许多涉及老年人的纵向研究来说，“20 岁”和“21 岁”将导致“失去的岁月” 参与者离开家中的安全环境进行抽血等活动是有风险的。两年的抽样损失对于涉及老年人的纵向研究尤其有害，包括 NIA 资助的 BIOCARD 研究于 1995 年开始，前瞻性地跟踪了超过 300 名认知正常的人中年参与者努力了解阿尔茨海默病（AD）的发病机制及其这个特征明确的队列每年都会接受详细的神经心理学测试和研究。每年两次进行 MRI、PET 和脑脊液采集，以了解 AD 的分子基础。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。使用 NoviPlex 卡在家中安全采集血样，但只能采集 2.5ul 血浆。收集——使用当前的蛋白质组学方法，如此数量的血浆无法产生深入的定量数据集。我们努力使用 NoviPlex 卡和最先进的技术集成家庭样本采集策略 Steen 实验室正在开发艺术样本保留分析策略（U24AI152179：高通量使用亚微升血浆来全面评估免疫状态的蛋白质组学）将允许在当前的 COVID-19 大流行期间安全地收集弱势患者的样本和数据。我们建议我们的平台将促进在以下地点收集的小量血浆的高质量数据采集：这种集成的样本保留收集和分析策略将允许以快速和简单的方式回家。研究人员继续从 BIOCARD 研究参与者那里收集有用的血浆样本，尽管在 BIOCARD 的这一关键阶段，COVID-19 正在持续流行，其中很大一部分鉴于参与者年事已高，他们正在表现出 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 NoviPlex 卡）血浆的蛋白质组（具体目标 1）并收集微毛细血管血浆远离纵向 BIOCARD 研究的活跃参与者（具体目标 2）。这项行政补充提案将增加对 Steen 博士现有 U24 的 AD 重点，这目前专注于样品保留血浆蛋白质组学测定。所要求的补充将使我们能够建立一种创新方法，促进微毛细血管血浆和高质量数据的远程收集 2021 年，来自独特 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，这对于广泛的纵向研究具有重要意义。