Biomarker for Sleep Loss: A Proteomic Determination

睡眠不足的生物标志物：蛋白质组学测定

• 批准号: 7935427
• 负责人: NIRMALA NIRINJINI NAIDOO
• 金额: $ 50万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 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 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7935427
• 关键词: Address; American; Area; Arts; Behavioral; Biological Markers; Blood; Blood Vessels; Blood specimen; Cardiac; Cardiovascular Diseases; Circadian Rhythms; Cognitive; Data; Diagnostic; Functional disorder; Genetic; Glucose; Health Personnel; High Pressure Liquid Chromatography; Hour; Human; Individual; Individual Differences; Insulin Resistance; Ion Exchange; Label; Mass Spectrum Analysis; Medical Errors; Molecular Profiling; Nurses; Obesity; Peptides; Performance; Phase; Physicians; Plasma; Population; Proteins; Proteomics; Protocols documentation; Recovery; Research Design; Resistance; Respiratory System; Respiratory tract structure; Risk; Risk Factors; Sampling; Schedule; Sleep; Sleep Deprivation; Technology; Therapeutic; Validation; Vehicle crash; Work; clinically relevant; healthy volunteer; novel; public health relevance; response

DESCRIPTION (provided by applicant): This application addresses broad Challenge Area (03): Biomarker Discovery and Validation and specific Challenge Topic, 03-HL-101: Identify and validate clinically relevant, quantifiable biomarkers of diagnostic and therapeutic responses for blood, vascular, cardiac, and respiratory tract dysfunction. Sleep loss is common in the American population. Some groups, such as health care workers (physicians, nurses), are particularly at risk for sleep loss because of their work schedules. Sleep loss has a major impact on cognitive performance with an increased risk of vehicular crashes, and medical errors. It also results in abnormalities in glucose handling (insulin resistance), increased obesity rates, and is a risk factor for cardiovascular disease. There are, however, major differences in the response to sleep loss between individuals and recent data indicate that this difference is in large part genetic. While these consequences and individual differences are known, there is currently no validated biomarker to assess sleep loss. This proposal plans to utilize a novel proteomic approach to identify biomarkers for sleep loss. Studies will be done in healthy volunteers, who had blood samples taken every 4 hours during a normal day, as well as during progressive sleep deprivation, and during recovery sleep. These human studies have already been conducted in 10 subjects who are relatively resistant to the effects of sleep deprivation (low responders) and 10 who show a marked behavioral response (high responders). PUBLIC HEALTH RELEVANCE: A state of the art proteomic approach will be applied to these already collected plasma samples to address two fundamental questions: (1) are there changes in proteins in blood with sleep deprivation, controlling for circadian influences, that can act as biomarkers for sleep loss; and (2) is the magnitude of change with sleep loss in candidate biomarkers different between subjects with a low response to sleep loss to those with a high response? To address these questions we will use an in-depth quantitative proteomic approach, combining isotopic labeling, a multidimensional protein identification technology (MudPIT) protocol and mass spectrometry, for high confidence identification of protein changes in the plasma of sleep deprived subjects. The proposed studies are designed to identify a biomarker for sleep loss. We hypothesize that there are molecular signatures that reflect the state of sleepiness. We will use a novel proteomic approach to identify proteins that change in response to sleep loss.

描述（由申请人提供）：此申请应解决广泛的挑战领域（03）：生物标志物发现和验证以及特定挑战主题，03-HL-101：识别和验证血液，血管，心动和呼吸道功能障碍的诊断和治疗反应的临床相关，可量化的生物标志物。在美国人口中，睡眠损失很普遍。一些小组，例如医疗保健工作者（医师，护士），由于他们的工作时间表，尤其有可能患睡眠不足的风险。睡眠损失对认知表现有重大影响，随着车辆撞车的风险增加和医疗错误。它还导致葡萄糖处理（胰岛素抵抗），肥胖率提高，是心血管疾病的危险因素。但是，在个人之间对睡眠损失的反应和最新数据表明，这种差异在很大程度上是遗传的。尽管已知这些后果和个体差异，但目前尚无验证的生物标志物来评估睡眠损失。该建议计划利用一种新型的蛋白质组学方法来识别睡眠损失的生物标志物。将在健康志愿者中进行研究，他们的志愿者在正常一天，渐进的睡眠剥夺和恢复睡眠期间每4小时每4小时采集血液样本。这些人类研究已经在10名受试者中对睡眠剥夺的影响（低反应者）和10名表现出明显的行为反应（高反应者）的影响。 公共卫生相关性：最先进的蛋白质组学方法将应用于这些已经收集的等离子体样本以解决两个基本问题：（1）（1）血液中蛋白质的血液中有剥夺睡眠，控制昼夜节律影响，可以充当睡眠损失的生物标志物； （2）在候选生物标志物的睡眠生物标志物的变化幅度是否与对患有较高反应的人的睡眠丧失反应较低的受试者之间的不同？为了解决这些问题，我们将使用深入的定量蛋白质组学方法，将同位素标记，多维蛋白质识别技术（MUDPIT）方案和质谱法结合在一起，以高度置信度，以高度置信度识别睡眠剥夺受试者血浆中的蛋白质变化。拟议的研究旨在确定睡眠损失的生物标志物。我们假设存在反映嗜睡状态的分子特征。我们将使用一种新型的蛋白质组学方法来识别因睡眠损失而改变的蛋白质。