Omics Data Generation Center (ODGC) for the Acute to Chronic Pain Signatures (A2CPS) Program

急性至慢性疼痛特征 (A2CPS) 计划的组学数据生成中心 (ODGC)

• 批准号: 10000873
• 负责人: Kathleen Marie Fisch
• 金额: $ 97.4万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 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/10000873
• 关键词: Acute; Acute Pain; Adult; Architecture; Biological; Biological Assay; Biological Markers; Brain; Caring; Clinical; Clinical Data; Collaborations; Collection; Data; Data Analyses; Data Coordinating Center; Development; Generations; Goals; Health; Human Resources; Image; Infrastructure; Intervention; Laboratories; Link; Longitudinal cohort; Management Information Systems; Medical; Mental Depression; Metadata; Methods; Microscopy; Molecular; Morbidity - disease rate; Multiomic Data; Musculoskeletal; Operative Surgical Procedures; Opiate Addiction; Pain; Participant; Patients; Peripheral Blood Mononuclear Cell; Population; Predisposition; Prevention approach; Prevention strategy; Preventive; Productivity; Proteomics; Protocols documentation; Public Health; Quality Control; Quality of life; Quantitative Reverse Transcriptase PCR; RNA; Reproducibility; Research Design; Research Personnel; Resolution; Resources; Sampling; Standardization; Technology; Trauma; Validation; Work; biosignature; candidate marker; chronic pain; clinical center; cohort; data analysis pipeline; data integration; data quality; data resource; data standards; data submission; disability; epigenomics; extracellular; extracellular vesicles; fecal microbiome; flexibility; genetic variant; high risk; imaging biomarker; liquid chromatography mass spectrometry; metabolomics; microbiome; microbiome analysis; novel; personalized approach; personalized strategies; prevent; primary outcome; programs; psychosocial; recruit; resilience; sample collection; screening; societal costs; success; transcriptome; transcriptome sequencing; transcriptomics

Omics Data Generation Center (ODGC) for the Acute to Chronic Pain Signatures (A2CPS) Program OVERALL PROJECT SUMMARY Chronic pain is a major health concern and one of the most common reasons adults seek medical care. It is associated with substantial morbidity linked to reduced quality of life, restricted mobility, depression, and opioid dependence. The biological mechanisms that prevent the resolution of acute pain after the initial insult and drive the transition from acute to chronic pain are poorly understood. The lack of rigorously validated biomarkers to predict which patients are more susceptible to the transition from acute to chronic pain states is thus a major gap hindering the development and implementation of population-wide and individualized preventive pain interventions. In the A2CPS Consortium, 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 A2CPS Omics Data Generation Center (ODGC), Aim 1, which will be executed in Year 1, will involve close collaboration with other components of the A2CPS Consortium 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 raw data to the DCC. The Administrative Core of the ODGC will establish a LIMS for sample and data tracking and recording of metadata. The ODGC will work closely with the DIRC/Data Integration and Analysis Component (DIAC) to establish data analysis pipelines. ODGC 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. Aims 2 and 3 will span Years 2-4, with Aim 2 focused on data generation 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 project is to establish the A2CPS Omics Data Generation Center to generate genetic variant, metabolomic, lipidomic, proteomic, exRNA, transcriptome, and microbiome data from two pain cohorts to validate 40 primary outcome biomarkers indicating susceptibility or resilience to development of chronic pain and identify novel biosignatures predicting the transition from acute to chronic pain.

急性至慢性疼痛特征 (A2CPS) 计划的组学数据生成中心 (ODGC) 全面的 项目概要 慢性疼痛是一个主要的健康问题，也是成年人寻求医疗护理的最常见原因之一。这是 与生活质量下降、活动受限、抑郁和阿片类药物相关的大量发病率相关 依赖性。最初的损伤和驱动后阻止急性疼痛消退的生物机制 人们对从急性疼痛到慢性疼痛的转变知之甚少。缺乏经过严格验证的生物标志物 因此，预测哪些患者更容易从急性疼痛状态转变为慢性疼痛状态是一个重大差距 阻碍全民和个体化预防性疼痛的发展和实施 干预措施。在 A2CPS 联盟中，临床中心将招募和收集临床数据和生物流体 样本来自两个纵向队列，每个队列有 1800 名受试者。将在 0、3 和 6 次收集生物流体样本 急性疼痛发作后几个月，包括特定的外科手术或特定的肌肉骨骼 创伤。这些样本将用于生成多组学数据，以验证 40 种主要结果生物标志物 表明对慢性疼痛发展的易感性或恢复力，以及确定新的候选者 生物标志物。对于拟议的 A2CPS 组学数据生成中心 (ODGC)，目标 1 将在 第一年，将与 A2CPS 联盟的其他组成部分密切合作，以建立最终的 研究设计和协议。所有 A2CPS 计划研究人员将共同努力建立 40 个主要项目 结果生物标志物。 ODGC 和临床中心研究者将共同决定具体样本 类型和收集/处理/存储方法。 ODGC 和数据集成资源中心/数据 协调部分 (DIRC/DCC) 调查人员将建立元数据和数据标准以及工作流程 用于向 DCC 提交元数据和原始数据。 ODGC 的行政核心将建立 LIMS 用于样本和数据跟踪以及元数据记录。 ODGC 将与 DIRC/Data 密切合作 集成和分析组件 (DIAC) 用于建立数据分析管道。 ODGC 调查人员还 预期参与 DIRC/DIAC 的综合分析，旨在开发疼痛特征 由多种生物标志物类型组成（包括分子、临床、心理社会和/或成像生物标志物） 表明对慢性疼痛的易感性/抵抗力，可用于制定针对慢性疼痛的个性化策略 预防和治疗慢性疼痛。目标 2 和 3 将跨越第 2-4 年，其中目标 2 侧重于数据 临床中心将收集约 11,000 个生物流体样本。目标 3 将涵盖 向 DIRC/DCC 提交元数据和数据、数据质量控制以及数据分析和 解释。该项目的主要目标是建立 A2CPS 组学数据生成中心 生成遗传变异、代谢组学、脂质组学、蛋白质组学、exRNA、转录组和微生物组数据 两个疼痛队列来验证 40 个主要结果生物标志物，表明发育的易感性或恢复力 慢性疼痛并确定预测从急性到慢性疼痛转变的新生物特征。