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

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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.