The Vanderbilt Urologic Infection Repository, a Resource for Personalized Clinical Discovery

范德比尔特泌尿感染存储库，个性化临床发现的资源

• 批准号: 10022297
• 负责人: Douglass Brooks Clayton
• 金额: $ 34万
• 依托单位: VANDERBILT UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-17 至 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10022297
• 关键词: Acinetobacter baumannii; Advisory Committees; Antimicrobial susceptibility; Area; Bacteriuria; Benign; Caring; Child; Clinical; Clinical Data; Communities; Community Outreach; Data; Databases; Diagnosis; Diagnostic; Disease; Education and Outreach; Educational Activities; Educational workshop; Electronic Health Record; Environment; Escherichia coli; Fostering; Foundations; Functional disorder; Funding; Genetic; Genetic Polymorphism; Genitourinary System Infection; Genitourinary system; Genomics; Genotype; Genus staphylococcus; Goals; Health; Heterogeneity; Human; Individual; Infection; Informatics; Infrastructure; Institution; Knowledge; Laboratories; Light; Link; Location; Logistics; Machine Learning; Maps; Medical; Medical Informatics; Medical Records; Microbe; Microbiology; Molecular; Organism; Outcome; Pathogenesis; Pathology; Patients; Phenotype; Physiology; Pilot Projects; Population; Published Comment; Records; Reporting; Resources; Risk Factors; Role; Science; Scientist; Services; Source; Specimen; Sum; Symptoms; Taxonomy; Technology; Urinary tract infection; Urine; Urologic Diseases; Urology; Uropathogen; Virulence Factors; Woman; base; biobank; biomedical resource; career development; clinical database; clinical infrastructure; clinical sequencing; combat; data dissemination; data mining; data space; data warehouse; demographics; functional genomics; genome sequencing; genome wide association study; health data; improved; individual patient; innovation; interest; member; men; microbial; microbial genome; microbiome; multidisciplinary; novel; operation; organizational structure; outcome forecast; pathogen; pathogenic microbe; patient health information; personalized care; personalized medicine; precision medicine; prevent; programs; repository; symptomatology; tool; translational impact; urinary; urologic; whole genome; young woman

SUMMARY - OVERALL In personalized medicine, the care of each patient is guided by his/her unique clinical circumstances. At its foundation, however, this paradigm holds a concurrent need for personalized science, in which technologies are developed and hypothesis explored in light of individual diversity. Critically, this diversity also includes unique microbial populations, which can augment the onset, progression, and treatment of disease. Within the field of benign urology, one of the most common pathologies—urinary tract infections (UTIs)—is also one of the most heterogenous, as the risk factors, symptomatology, and outcomes can vary significantly from patient to patient. Not surprisingly, the complexity of UTIs extends beyond the host, with tremendous genotypic and phenotypic diversity among the species/strains of microbes that elicit these infections. To better align the management of UTIs with the goals of precision care, our understanding of pathophysiology must become more nuanced, as we network in tandem the inherent diversity of host and microbe. To these ends, we propose a resource that provides an interconnected picture of both components, the Vanderbilt Urologic Infection Repository (VUIR). With our institution's unique foundation in medical informatics, we will create a searchable database of clinical parameters from bacteriuric patients (many thousands of cases annually), together with microbiologic data on the organisms. In parallel, the paired microbial strains will be stored permanently as a biobank for analysis and experimentation, together with linkage to anonymized versions of patient records within Vanderbilt's Synthetic Derivative (a filtered version of our electronic health data). The logistical infrastructure for clinical biobanking is also already in place at Vanderbilt via the institutionally-supported microVU initiative, in which microbial isolates from the diagnostic laboratory are repurposed as academic resources. As a basic expansion of these efforts, the VUIR will represent a first-in-kind tool for developing technologies to combat UTIs, while also investigating their underlying pathogenesis. In particular, it could facilitate functional genomic studies that bridge host and pathogen. Demonstrating the resource's value, we will conduct whole-genome sequencing of clinically underrepresented bacterial species, together with genome-wide association studies that focus on the infection phenotypes of the source-patients. In addition to novel virulence factors, we seek to identify elusive genomic determinants that distinguish cases of asymptomatic bacteriuria (ASB) and symptomatic UTI. The molecular basis of UTI-versus-ASB epitomizes a clinical challenge that requires integration of host and pathogen, as provided by the VUIR. Finally, to support the program and its discoveries, we propose an organizational structure of multidisciplinary content-area experts and dedicated support staff. Along with coordinating daily activities and assuring seamless dissemination of data/specimens, this Administrative Core (AdCore) will champion educational activities and additional pilot projects that build upon the resource. In sum, the VUIR stands to generate actionable discoveries from the human and microbial diversity of UTIs—not in spite of it.

摘要-总体 在个性化医疗中，每个病人的护理都是由他/她独特的临床情况指导的。第 然而，这种范式同时需要个性化的科学，在这种科学中， 根据个体多样性发展和探索假设。重要的是，这种多样性还包括独特的 微生物种群，这可以增加疾病的发作，进展和治疗。领域内 良性泌尿系统疾病，最常见的病理之一-尿路感染（UTI）-也是最常见的疾病之一。 异质性，因为风险因素、病理学和结局可能因患者而异。 毫不奇怪，UTI的复杂性超出了宿主，具有巨大的基因型和表型差异。 引起这些感染的微生物物种/菌株之间的多样性。为了更好地协调 为了实现精确护理的目标，我们对病理生理学的理解必须变得更加细致入微， 宿主和微生物固有的多样性串联成网络。为此，我们提出一种资源， 提供了两个组件的相互关联的图片，范德比尔特泌尿系统感染库 （VUIR）.凭借我们机构在医学信息学方面的独特基础，我们将创建一个可搜索的数据库， 细菌尿患者的临床参数（每年数千例），以及微生物 生物体的数据。同时，配对的微生物菌株将作为生物库永久储存， 分析和实验，以及与范德比尔特的病人记录的匿名版本的链接， 合成衍生物（我们的电子健康数据的过滤版本）。临床的后勤基础设施 生物库也已经通过机构支持的microVU计划在范德比尔特到位，其中 来自诊断实验室的微生物分离物被重新用作学术资源。作为一个基本的扩展 在这些努力中，VUIR将成为开发对抗UTI技术的第一个同类工具，同时， 研究其潜在的发病机制。特别是，它可以促进功能基因组研究， 寄主和病原体。为了展示资源的价值，我们将进行临床上的全基因组测序， 代表性不足的细菌物种，以及关注感染的全基因组关联研究 来源患者的表型。除了新的毒力因子外，我们还试图鉴定难以捉摸的基因组 区分无症状菌尿（ASB）和有症状UTI的决定因素。分子 UTI与ASB的基础集中体现了一个临床挑战，需要宿主和病原体的整合， 由VUIR提供。最后，为了支持该计划及其发现，我们提出了一个组织结构 由多学科内容领域专家和专职支持人员组成。沿着协调日常活动， 确保数据/标本的无缝传播，该管理核心（AdCore）将支持 教育活动和更多的试点项目，建立在资源。总而言之，VUIR将 从UTI的人类和微生物多样性中产生可操作的发现-而不是尽管如此。