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

描述(申请人提供)：翻译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，迫使研究人员要么采用全面但有创的方法(例如，静脉穿刺后的基因组图谱)，要么采用微创但非综合的方法(如唾液分析)。瞄准。我们的目标是通过测试微创采血方法，即干血斑和毛细血管采血，是否可以用来检测与压力相关的全基因组表达模式的变化，从而验证一种全面和微创的方法来研究人类的应激生物学。方法：研究方法。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点、毛细血管血和静脉血中收集RNA。然后，我们将测试来自微创标本收集程序的基因组图谱的可靠性、有效性和敏感性。在临床验证中，这些测试将为样本采集选择干血点或毛细血管血提供信息。其次，为了进行临床验证，我们将要求具有人口代表性的1250对16岁英国同卵双胞胎样本，随后进行双胞胎早期发展研究(TEDS)，以完成感知压力量表的计算机化版本，我们将选择这一衡量标准中最不和谐的35对双胞胎。然后，我们将测试微创分析中的微阵列分析是否可以识别具有相同DNA序列但暴露在不同压力下的一对年轻个体的基因表达差异。这意味着什么。研究压力基因组指纹的微创分析方法的验证将为研究人员提供在更大、更具人群代表性和更年轻的人类样本中进行压力生物学综合评估所需的技术。 公共卫生相关性：翻译应激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应激相关的生物学变化。我们建议开展一种安全、简单和相对无痛的程序来研究全基因组表达模式中与应激相关的变化。该项目将为研究人员提供在更大、更年轻、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。

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.