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

急性到慢性疼痛信号(A2CPS)计划的组学数据生成中心(ODGC) 总体来说 项目总结 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。它是 与生活质量降低、活动受限、抑郁和阿片类药物相关的实质性发病率 依赖。阻止在最初的侮辱和驱使后缓解急性疼痛的生物学机制 从急性疼痛到慢性疼痛的过渡过程还知之甚少。缺乏经过严格验证的生物标记物 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主要的差距 阻碍全民和个性化预防疼痛的发展和实施 干预措施。在A2CPS联合体中，临床中心将招募和收集临床数据和生物液 样本来自两个纵向队列，每个队列有1800名受试者。将采集0、3和6个生物体液样本 急性疼痛发作几个月后，包括特定的外科手术或特定的肌肉骨骼 精神创伤。这些样本将被用来产生多组数据，以验证40个主要结果生物标志物 表明对慢性疼痛的易感性或恢复力，以及确定新的候选对象 生物标志物。对于拟议的A2CPS Omics数据生成中心(ODGC)，目标1，将于#年执行 第一年，将与A2CPS财团的其他组件密切合作，以建立最终的 研究设计和协议。所有A2CPS计划调查人员将共同努力，建立40个初选 结果生物标志物。ODGC和临床中心的调查人员将共同决定具体的样本 类型(S)和收集/处理/存储方法。ODGC和数据集成资源中心/数据 协调部门(DIRC/DCC)调查员将建立元数据和数据标准以及工作流程 向发改委提交元数据和原始数据。检察官办公室的行政核心将建立一个LIMS 用于样本和数据跟踪以及元数据记录。国际数据中心将与信息和通信技术中心/数据中心密切合作 集成和分析组件(DIAC)，用于建立数据分析管道。ODGC调查人员还 期望与DIRC/DIAC一起参与旨在开发疼痛信号的综合分析 由多种生物标记物类型组成(包括分子、临床、心理和/或成像生物标记物) 指示对慢性疼痛的敏感性/弹性，可用于制定个性化策略 预防和治疗慢性疼痛。目标2和目标3将跨越2-4年，目标2侧重于数据 从临床中心将收集的约11,000个生物液样本中产生。目标3将包括 向DIRC/DCC提交元数据和数据、数据质量控制、数据分析和 释义。该项目的主要目标是建立A2CPS Omics数据生成中心，以 生成遗传变异、代谢组、脂组、蛋白质组、exRNA、转录组和微生物组数据 两个疼痛队列验证40个指示发育易感性或弹性的主要结果生物标记物 并确定新的生物特征，预测从急性疼痛到慢性疼痛的转变。

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.