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）： 我们的目标是在使用全面的RNA测序中，在健康人类的12种不同体液的样品中生成短，长和循环的非编码调节EXRNA的参考曲线，包括环境衍生的EXRNA。我们组建了一个具有临床研究，基因组技术，生物信息学和统计学的专业知识的多学科团队 实现这一目标。该提案的一个主要优势是，我们与参与两个基于UCSF的U19项目的其他研究人员的密切互动受益，这些项目得到了普通基金细胞外RNA通信计划的支持。另一个主要优势是，我们将利用大量精心策划的体液样本，这些样本从参加NIH资助的队列研究的女性和男女儿童和成人种群中收集。我们的三个具体目的是：目标1）从12种人体液体（血浆，血清，血清血液，尿液，尿液，脑脊液（CSF），痰液，支气管肺泡灌洗（BAL），唾液，唾液，唾液，羊毛流体，羊膜液体液体效应的液体液体效果）的大量样品（血清，血清，脐带血，尿液，尿液（CSF），支气管肺泡灌洗（BAL），唾液中）序列体液样品中的全部EXRNA范围，AIM 3）采用适当的分析方法来识别人类和外源性RNA，并为代表性的种族多样性人群建立正常参考值。我们将分两个阶段对该项目进行处理。在第一阶段（1 - 2年）中，我们将使用三种互补测序方法研究约200个代表12种体液的样品。这些研究将填补我们对人体流体中exrnas多样性的理解的主要空白，并就哪些基于测序的方法最有价值地识别和定量提供了重要的见解。在II阶段（3 - 5年）期间，我们将通过分析2,880个血浆和尿液样本来建立I阶段的研究和其他由细胞外RNA通信计划参与者进行的工作，这些等离子体和尿液样本已从在三个大型的，种族多元化的大型，NIH，NIH队列研究（Cardia，Cardia，Cardia，carta，carka，carka和Gala/gala/gala/cala/sage）中纳入的2,160个受试者。这些研究将充分发挥作用，以建立按年龄，性别和种族分层的Exrnas的正常参考范围。每个阶段都与现实的里程碑评估相关联，可以构成与其他财团参与者合作的基础。该项目与The Int的公共卫生有关，将建立将ExrNA作为患有或处于疾病风险的患者的生物标志物所需的健康控制参考数据。