ECHO Laboratory Core at Vanderbilt for Integrated Sample Biobanking and Processing

总结 早期生活环境暴露（例如，社会环境、父母风险因素、尼古丁、饮食、感染）， 越来越多地涉及具有终身后果的儿童疾病的早期发病机制。 将这些风险与长期结果联系起来的机制仍然有限。2016年，NIH成立了 环境对儿童健康结果的影响（ECHO）计划，一个合作的多维 研究倡议，以说明生命早期环境因素对儿童健康的影响（超过70个群组， > 50K参与者）。虽然ECHO中的靶向测定可能导致疾病特异性的洞察力，但广泛， 对新发现的分子空间进行全面、公正的评估，这是ECHO的一项关键使命， 将需要集中生物样本库工作/实验室管理，具有高通量能力 “OMICs”/非“OMICs”测定以及新型测定开发、生物信息学和云架构/数据 分享科学合作。作为对RFA-OD-22 - 016的回应，范德比尔特将通过以下方式满足这一需求： 在范德比尔特建立ECHO实验室核心，用于集成样本生物库和处理 （ELVIS）。ELVIS促进生物标本的收集和处理;管理生物储存库;执行 广泛的生物标本检测（包括新的开发），并协调元数据和检测数据 转移到协调中心。ELVIS以核心"资源"的形式进行组织，以提供领导/整合， 管理ECHO生物库、检测性能和数据交付：（1）行政/LIMS/生物库;（2） 代谢组学;（3）蛋白质组学;（4）核酸评估;（5）宏基因组学;（6）生物信息学/研究设计。 我们在这一计划中处于独特的地位，利用范德比尔特独特的长期战略投资， 功能性生物库和分析：（1）大规模、可靠的生物库接收和实验室管理 （"LIMS"）能力（目前有生物标本的患者> 35万;许多其他NIH资助的生物库）;（2）全国范围内 公认的临床元数据采集系统（REDCap，REDBrics;用于NIH倡议，如All of Us）;（3） 尖端的实验室核心，具有开发/验证新型检测方法的能力。我们将建立 ECHO队列生物标本采集和跟踪基础设施的统一方案和工作流程， 从样本收集点到长期储存（目标1）;执行高质量、功能强大的多OMIC， 有针对性的检测，以确定生命早期疾病轨迹的分子相关性（目标2），并提供 综合数据管理平台，以促进综合数据分析（目标3）。ELVIS是一种理想 ECHO的机制给予（1）在处理银行业所需样本量方面有深厚的资金经验， 高通量检测，包括质量保证措施;（2）在ECHO的既往跟踪记录，以确保ECHO- 具体的元数据收集、管理和协调;（3）数据云基础设施的安全方法 分析管道和数据流到临床站点和数据分析中心。成功完成将使 ECHO的使命是发现幼儿疾病决定因素的分子基础。

SUMMARY Early-life environmental exposures (e.g., social-environmental, parental risk factors, nicotine, diet, infection) are increasingly implicated in the early pathogenesis of childhood diseases that have life-long consequences. Mechanisms linking these exposures to longer-term outcomes remain limited. In 2016, the NIH established the Environmental influences on Child Health Outcomes (ECHO) Program, a collaborative multi-dimensional research initiative to characterize the impact of early-life environmental factors on childhood health (>70 cohorts, >50K participants). While targeted assays within ECHO are likely to lead to disease-specific insight, broad, comprehensive, unbiased assessment of the molecular space for novel discovery—a key mission of ECHO— will necessitate centralization of biobanking efforts/laboratory management with capability for high-throughput “OMICs”/non-“OMICs” assay as well as novel assay development, bioinformatics, and cloud architecture/data sharing for collaborative science. In response to RFA-OD-22-016, Vanderbilt will address this need by establishing the ECHO Laboratory Core at Vanderbilt for Integrated Sample Biobanking and Processing (ELVIS). ELVIS facilitates the collection and processing of biospecimens; manages the biorepository; performs a wide range of biospecimen assays (including novel development), and coordinates metadata and assay data transfer to the Coordinating Center. ELVIS is organized in core “resources” to provide leadership/integration to manage ECHO biobanking, assay performance, and data delivery: (1) administrative/LIMS/biobanking; (2) metabolomics; (3) proteomics; (4) nucleic acid assessment; (5) metagenomics; (6) bioinformatics/study design. We are uniquely positioned for this initiative, leveraging Vanderbilt’s unique long-term strategic investment in functional biobanking and assay: (1) large-scale, reliable biorepository receipt and laboratory management (“LIMS”) capability (>350K patients currently with biospecimens; many other NIH funded biobanks); (2) nationally recognized systems for clinical metadata capture (REDCap, REDBrics; used in NIH initiatives, like All of Us); (3) cutting-edge laboratory cores with capability for novel assay development/validation. We will establish harmonized protocols and workflow for ECHO cohort biospecimen collection and tracking infrastructure from the point of sample collection to long-term storage (Aim 1); perform high-quality, well-powered multi-OMICs and targeted assays to identify molecular correlates of disease trajectories in early life (Aim 2), and provide comprehensive data management platform to facilitate integrated data analysis (Aim 3). ELVIS is an ideal mechanism for ECHO given (1) deep, funded experience in handling the requisite sample sizes in banking and high-throughput assay, including quality assurance measures; (2) prior track record in ECHO to ensure ECHO- specific metadata collection, curation, and harmonization; (3) secure methods for cloud infrastructure for data analysis pipelines and data flow to clinical sites and data analysis center. Successful completion will enable the success of ECHO’s mission to discover molecular underpinnings of early childhood determinants of disease.