Defining A Comprehensive Reference Profile of Circulating Human Extracellular RNA

定义循环人类细胞外 RNA 的综合参考谱

• 批准号: 8775079
• 负责人: David J Erle
• 金额: $ 70万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8775079
• 关键词: Adult; Age; Amniotic Fluid; Base Sequence; Bioinformatics; Biological Markers; Blood; Body Fluids; Bronchoalveolar Lavage; Cells; Cerebrospinal Fluid; Child; Childhood; Clinical; Clinical Trials; Cohort Studies; Collaborations; Communication Programs; Consultations; Data; Development; Diagnostic; Disease; Embryonic Fluid; Enrollment; Epidemiologic Studies; Ethnic Origin; Female; Fractionation; Functional RNA; Funding; GALA; Gender; Gene Expression Profile; Genomics; Goals; Health; Human; Human body; Hydrolysis; Infection; Inflammation; Interdisciplinary Study; Laboratories; Libraries; Liquid substance; Malignant Neoplasms; Metadata; Methods; Ovarian Follicle; Participant; Patients; Phase; Plasma; Population; Population Heterogeneity; Preparation; Production; Public Health; RNA; RNA Sequences; Reference Values; Research Personnel; Research Project Grants; Ribonucleases; Robotics; Saliva; Sampling; Seminal fluid; Site; Small RNA; Source; Sputum; Technology; Therapeutic; Umbilical Cord Blood; United States National Institutes of Health; Universities; Urine; Work; base; circular RNA; data sharing; disorder risk; experience; extracellular; insight; interest; male; metagenome; microbial; multidisciplinary; phase 1 study; public health relevance; sex; statistics; transcriptome sequencing

DESCRIPTION (provided by applicant): Our goal is to generate reference profiles of short, long and circular non-coding regulatory exRNAs, including environmentally-derived exRNAs, in samples of 12 different body fluids from healthy humans using comprehensive RNA sequencing. We have assembled a multidisciplinary team with expertise in clinical investigation, genomics technologies, bioinformatics and statistics to achieve this goal. One major strength of this proposal is that we benefit from close interactions with other investigators participating in two UCSF-based U19 projects supported by the Common Fund Extracellular RNA Communication Program. Another major strength is that we will make use of very large sets of carefully curated body fluid samples collected from ethnically diverse populations of female and male children and adults who participated in NIH-funded cohort studies. Our three specific aims are: Aim 1) Obtain a large and diverse set of samples from 12 human body fluids (plasma, serum, cord blood, urine, cerebrospinal fluid (CSF), sputum, bronchoalveolar lavage (BAL), saliva, seminal fluid, amniotic fluid, peri-embryonic fluid and ovarian follicle fluid), Aim 2) Use state of the art approaches to sequence the full range of exRNAs in body fluid samples, and Aim 3) Apply appropriate analytical approaches to identify human and exogenous RNAs and establish normal reference values for representative ethnically-diverse US populations. We will approach the project in two phases. In phase I (years 1-2), we will study ~200 samples representing 12 body fluids using three complementary sequencing approaches. These studies will fill major gaps in our understanding of the diversity of exRNAs in human body fluids and provide important insights about which sequencing-based approaches are most valuable for exRNA identification and quantification. During phase II (years 3-5), we will build on our phase I studies and other work performed by Extracellular RNA Communication Program participants by analyzing 2,880 plasma and urine samples that have been banked from 2,160 subjects enrolled in three large, ethnically-diverse, NIH cohort studies (CARDIA, REGARDS and GALA/SAGE). These studies will be adequately powered to establish normal reference ranges for exRNAs stratified by age, sex, and ethnicity. Each phase is associated with realistic milestone assessments and can form the basis for collaboration with other consortium participants. This project is relevant to public health in thatit will establish the healthy control reference data necessary to apply exRNAs as biomarkers in patients with or at risk for disease.

描述（由申请人提供）： 我们的目标是利用全面的 RNA 测序，在健康人 12 种不同体液样本中生成短、长和环状非编码调节 exRNA（包括环境来源的 exRNA）的参考图谱。我们组建了一支多学科团队，拥有临床研究、基因组技术、生物信息学和统计学方面的专业知识 为了实现这个目标。该提案的一个主要优点是，我们受益于与参与共同基金细胞外 RNA 通讯计划支持的两个基于 UCSF 的 U19 项目的其他研究人员的密切互动。另一个主要优势是，我们将利用大量精心挑选的体液样本，这些样本是从参与 NIH 资助的队列研究的不同种族的男女儿童和成人群体中收集的。我们的三个具体目标是：目标 1) 从 12 种人体体液（血浆、血清、脐带血、尿液、脑脊液 (CSF)、痰、支气管肺泡灌洗液 (BAL)、唾液、精液、羊水、胚胎周围液和卵巢卵泡液）中获取大量不同的样本，目标 2) 使用最先进的方法 对体液样本中的全部 exRNA 进行测序，目标 3) 应用适当的分析方法来识别人类和外源 RNA，并为具有代表性的美国多样化种族人群建立正常参考值。我们将分两个阶段实施该项目。在第一阶段（第 1-2 年），我们将使用三种互补测序方法研究代表 12 种体液的约 200 个样本。这些研究将填补我们对人体体液中 exRNA 多样性理解的主要空白，并提供关于哪些基于测序的方法对于 exRNA 识别和定量最有价值的重要见解。在第二阶段（第 3-5 年）期间，我们将在第一阶段研究和细胞外 RNA 通讯计划参与者进行的其他工作的基础上，分析 2,880 份血浆和尿液样本，这些样本来自参加三项大型、种族多样化的 NIH 队列研究（CARDIA、REGARDS 和 GALA/SAGE）的 2,160 名受试者。这些研究将有足够的动力来建立按年龄、性别和种族分层的 exRNA 的正常参考范围。每个阶段都与现实的里程碑评估相关联，并且可以构成与其他联盟参与者合作的基础。该项目与公共卫生相关，因为它将建立应用 exRNA 作为患有疾病或有患病风险的患者的生物标志物所需的健康对照参考数据。