Laboratory and clinical validation of a minimally-invasive assay to study the gen

研究基因的微创测定的实验室和临床验证

• 批准号: 8174174
• 负责人: Andrea Danese
• 金额: $ 13.77万
• 依托单位: KING'S COLLEGE LONDON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8174174
• 关键词: 16 year old; Adolescent; Advertisements; Agreement; Binding; Biological; Biological Assay; Biology; Blood; Blood Specimen Collection; Blood capillaries; Clinical; Collection; DNA Sequence; Data; Development; Disease; Exposure to; Fingerprint; Functional disorder; Gene Cluster; Gene Expression; Genes; Genetic Predisposition to Disease; Genomics; Human; Individual; Laboratories; London; Measures; Methods; Microarray Analysis; Monozygotic Twinning; Monozygotic twins; Painless; Participant; Pattern; Population; Procedures; Psychological Stress; RNA; Recruitment Activity; Reporting; Research; Research Personnel; Running; Sampling; Spottings; Stress; Technology; Testing; Twin Multiple Birth; Validation; Validity and Reliability; Venipunctures; Venous; base; capillary; college; computerized; genome-wide; healthy volunteer; minimally invasive; salivary assay; sample collection

DESCRIPTION (provided by applicant): Translational stress research has aimed to elucidate the biological mechanisms through which psychological stress influences disease pathophysiology in humans. Advancement in this field has been challenged by a technology gap that forces researchers to employ either comprehensive but invasive methods (e.g., genomic profiling after venipuncture) or minimally-invasive but non-comprehensive methods (e.g., salivary assays). AIM. We aim to validate a comprehensive and minimally-invasive method to study stress biology in humans, by testing whether minimally-invasive blood collection methods, namely dried blood spots and capillary blood collection, could be used to detect stress-related changes in genome-wide expression patterns. METHODS. First, for laboratory validation, we will collect RNA from dried blood spots, capillary blood, and venous blood in 10 healthy volunteers. We will then test the reliability, the validity, and the sensitivity of genomic profiles from minimally-invasive specimen-collection procedures. These tests will inform the choice of dried blood spots or capillary blood for specimen collection in a clinical validation. Second, for clinical validation, we will ask a population-representative sample of 1,250 pairs of 16-year-old UK monozygotic twins followed-up by the Twins Early Development Study (TEDS) to complete a computerized version of the Perceived Stress Scale and we will select the 35 most discordant twin pairs on this measure. We will then test whether microarray analysis from minimally-invasive assays can identify gene expression differences in pairs of young individuals with identical DNA sequences but different exposure to stress. IMPLICATIONS. The validation of a minimally-invasive assay to study the genomic fingerprint of stress will provide researchers with the technology needed to perform comprehensive assessment of stress biology in larger, more population-representative, and younger human samples. PUBLIC HEALTH RELEVANCE: A critical barrier to the advancement of translational stress research is the lack of minimally-invasive and comprehensive methods to assess stress-related biological changes in humans. We propose to carry out the validation of a safe, simple and comparatively painless procedure to study stress-related changes in genome-wide expression patterns. This project will provide researchers with the technology needed to perform comprehensive assessment of stress biology in larger, younger and more population-representative human samples.

描述（由申请人提供）：转化应激研究旨在阐明心理应激影响人类疾病病理生理学的生物学机制。这一领域的进步受到了技术差距的挑战，这迫使研究人员采用全面但侵入性的方法（例如，静脉穿刺后的基因组分析）或微创但不全面的方法（例如，唾液测定）。目标。我们的目标是验证一个全面的和微创的方法来研究人类的压力生物学，通过测试是否微创血液采集方法，即干血斑和毛细血管血液采集，可以用来检测压力相关的变化在全基因组表达模式。方法.首先，为了进行实验室验证，我们将从10名健康志愿者的干血斑、毛细血管血和静脉血中收集RNA。然后，我们将测试的可靠性，有效性，和敏感性的基因组图谱从微创肿瘤收集程序。这些检测将为临床验证中样本采集的干血斑或毛细血管血的选择提供信息。第二，为了临床验证，我们将要求1,250对16岁的英国单卵双胞胎的人口代表性样本，通过双胞胎早期发展研究（TEDS）进行随访，以完成感知压力量表的计算机版本，我们将选择35对最不一致的双胞胎对。然后，我们将测试微阵列分析从微创检测是否可以识别基因表达差异的年轻人对相同的DNA序列，但不同的压力暴露。含义。研究压力基因组指纹的微创检测方法的验证将为研究人员提供在更大，更具人口代表性和更年轻的人类样本中进行压力生物学全面评估所需的技术。 公共卫生关系：翻译压力研究进展的一个关键障碍是缺乏微创和全面的方法来评估人类与压力相关的生物学变化。我们建议进行一个安全，简单和相对无痛的程序来研究压力相关的变化，在全基因组表达模式的验证。该项目将为研究人员提供在更大，更年轻和更具人口代表性的人类样本中进行压力生物学综合评估所需的技术。