A2CPS ExRNA Component

A2CPS ExRNA 成分

基本信息

批准号：
10000903
负责人：
LOUISE CHANG LAURENT
金额：
$ 35.46万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10000903
关键词：
Acute Acute Pain Adopted Biological Markers Cells Clinical Clinical Data Collaborations Collection Communication Data Data Analyses Data Coordinating Center Data Set Detection Development Ensure Equilibrium Generations Goals Human Human Resources Knowledge Laboratories Libraries Longitudinal cohort Management Information Systems Measurement Mediation Mediator of activation protein Metadata Methods MicroRNAs Molecular Multiomic Data Musculoskeletal Operative Surgical Procedures Pain Play Predisposition Preparation Prevention Prevention strategy Procedures Process Protocols documentation Quality Control Quantitative Reverse Transcriptase PCR RNA Reproducibility Reproducibility of Results Research Design Research Personnel Resources Risk Role Running Sample Size Sampling Stimulus Testing Tissues Trauma Validation Work biomarker discovery biomarker identification biomarker validation candidate marker candidate selection chronic pain clinical center cohort comparative data analysis pipeline data integration data standards data submission extracellular extracellular vesicles imaging biomarker miniaturize novel pain signal patient biomarkers personalized strategies primary outcome programs psychosocial recruit resilience sample collection skills therapeutic target transcriptome sequencing transcriptomics

项目摘要

EXTRACELLAR RNA COMPONENT SUMMARY Extracellular RNAs (exRNAs) have been found in all tested human biofluids, and there is increasing evidence that they play a role in pain mediation and modulation, and can serve as biomarkers for identification of those at risk for transitioning to chronic pain after an acute pain episode. This project is the exRNA Component of the Omics Data Generation Center (ODGC) for the Acute to Chronic Pain Signatures (A2CPS) Program. In this Program, the Clinical Centers will recruit and collect clinical data and biofluid samples from two longitudinal cohorts of 1800 subjects each. Biofluid samples will be collected 0, 3, and 6 months after an acute pain episode, consisting of a specific surgical procedure or a specific musculoskeletal trauma. These samples will be used to generate multi-omic data to validate 40 primary outcome biomarkers indicating susceptibility or resilience to development of chronic pain, as well as to identify new candidate biomarkers. For the proposed exRNA Component, Aim 1, which will be executed in Year 1, will involve close collaboration with other components of the A2CPS Program to establish the final study design and protocols. All of the A2CPS Program investigators will work together to establish the 40 primary outcome biomarkers. The ODGC and Clinical Center investigators will jointly decide on the specific sample type(s) and collection/processing/storage methods. The ODGC and Data integration Resource Center/Data Coordination Component (DIRC/DCC) investigators will establish Metadata and Data Standards and a workflow for submission of metadata and data to the DCC. The exRNA Component and the Administrative Core of the ODGC will establish a LIMS for sample and data tracking, and recording of metadata. The exRNA Component and DIRC/Data Integration and Analysis Component (DIAC) will establish qRT-PCR and small RNAseq data analysis pipelines. Aims 2 and 3 will span Years 2-4, with Aim 2 focused on isolation and qRT-PCR and small RNAseq profiling of exRNA from the ~11,000 biofluid samples that will be collected by the Clinical Centers. Aim 3 will encompass submission of metadata and data to the DIRC/DCC, quality control of the data, and data analysis and interpretation. The primary goal of this Component is generation and submission of high-quality exRNA qRT-PCR and small RNAseq data for validation of pre- selected candidate exRNA biomarkers and discovery of novel exRNA biomarkers. The exRNA component investigators also anticipate participating in integrative analyses with the DIRC/DIAC aimed at developing pain signatures comprised of multiple biomarker types (including molecular, clinical, psychosocial, and/or imaging biomarkers) indicating susceptibility/resilience to chronic pain, which can be used to develop personalized strategies for prevention and treatment of chronic pain. The personnel for this proposed exRNA Component have acquired the necessary skills and knowledge to successfully execute this project from participation in the Extracellular RNA Communication Consortium, including high-throughput workflows for extracellular vesicle- specific and total exRNA isolation and small RNAseq library preparation and exRNA data analysis pipelines.

外部RNA分量概括在所有测试的人类生物流体中都发现了细胞外RNA（EXRNA），并且有越来越多的证据他们在疼痛中调解和调节中发挥了作用，可以作为识别那些人的生物标志物急性疼痛发作后过渡到慢性疼痛的风险。这个项目是急性到慢性疼痛特征（A2CPS）程序的OMICS数据生成中心（ODGC）。在这个程序，临床中心将招募和收集两个纵向的临床数据和生物流体样品每个由1800名受试者组成的队列。生物流体样品将在急性疼痛发作后0、3和6个月收集，由特定的外科手术或特定的肌肉骨骼创伤组成。这些样本将用于生成多摩变数据以验证40个主要结果生物标志物，表明对慢性疼痛的发展以及鉴定新候选生物标志物。对于所提出的Exrna 组件，AIM 1（将在1年级执行）将涉及与其他组件的密切合作 A2CPS计划建立最终的研究设计和协议。所有A2CPS计划调查人员将共同建立40个主要结果生物标志物。 ODGC和临床中心研究人员将共同决定特定的样本类型和收集/处理/存储方法。 ODGC和数据集成资源中心/数据协调组件（DIRC/DCC）研究人员将建立元数据和数据标准以及提交元数据和数据向DCC提交的工作流程。 Exrna ODGC的组件和管理核心将建立用于样本和数据跟踪的LIM，以及记录元数据。 ExRNA组件和DIRC/数据集成和分析组件（DIAC）将建立QRT-PCR和小型RNASEQ数据分析管道。目标2和3将跨越2 - 4年，AIM 2 侧重于隔离和QRT-PCR和exRNA的小rnaseq分析，从约11,000个生物流体样品中将由临床中心收集。 AIM 3将涵盖元数据和数据的提交 DIRC/DCC，数据的质量控制以及数据分析和解释。该组件的主要目标是生成和提交高质量的EXRNA QRT-PCR和小的RNASEQ数据，以验证前选定的候选exrna生物标志物和新型Exrna生物标志物的发现。 ExRNA分量调查人员还预计，与DIRC/DIAC旨在发展疼痛的综合分析由多种生物标志物类型组成的特征（包括分子，临床，社会心理和/或成像生物标志物）表明对慢性疼痛的敏感性/韧性，可用于开发个性化预防和治疗慢性疼痛的策略。该提议的ExRNA组件的人员已经获得了必要的技能和知识，以成功地执行该项目细胞外RNA通信联盟，包括用于细胞外囊泡的高通量工作流程特异性和总exRNA分离以及小的RNASEQ库制备和ExRNA数据分析管道。