Virome Investigation in Diverse Human Populations - PROJECT SUMMARY/ABSTRACT (OVERALL): The composition, diversity, and dynamics of all viruses found inside and on the human body–the human virome–remains poorly understood. The goal of our Human Virome Program (HVP) Virome Characterization Center (VCC) is to discover and curate the spectrum of viruses present in humans, and to characterize key features of their biology and dynamics, including mapping viral tropism, monitoring changes over time, identifying differences, and cataloging all phages. The VCC will leverage a combination of genomics, transcriptomics, imaging, and computational approaches to develop a systematic, multimodal approach for mapping and understanding the human virome and its diversity in precise detail and at scale. We will establish a bespoke specimen collection for this purpose, leveraged from five existing large, longitudinal and diverse cohorts that share a common study design, collectively encompassing >350,000 participants across all 55 U.S. states and territories. From it, our Biospecimen Collection Core (BCC) will select a diverse 4,000-participant cohort of varying ages, sex/gender, geographic origin, and racial/ethnic diversity, which will be processed by the Biospecimen Analysis Core (BAC) using existing cutting-edge metagenomic and other omics approaches, and as needed developing and adapting new methods to improve viral genome recovery and characterization. The Data Analysis and Submission Core (DASC) will use state-of-the-art computational approaches to process, store, analyze, and release these data. The Ethical Legal and Societal Implications (ELSI) core will manage the responsible engagement with participants and explore how findings can be effectively communicated to participants. The VCC, comprised of investigators from the Broad Institute, Brigham and Women’s Hospital, and Harvard T.H. Chan School of Public Health, emphasizes effective leadership and collaboration among its five cores. It will be led by a team of experts in diverse areas, including viral genomics, the human microbiome, bioinformatics, technology development, and management of large cohort studies. The Administrative Core (AC) will establish and implement the project plan with clear milestones, metrics, and contingency plans to achieve its goals. The timeline encompasses participant engagement, sample retrieval, data processing, and analytics, with ongoing evaluation and proactive measures to identify and address potential challenges. The AC will also implement a Plan to Enhance Diverse Perspectives (PEDP) for the study team and participants. The VCC is committed to rapid and open sharing of all resources generated, including data, reagents, protocols, and tools, through public repositories, journals, and collaboration with other VCCs. Through the project, we will develop an innovative and comprehensive approach to characterizing the human virome, to understand what constitutes and modulates the virome and how it influences human health, and disseminate the outcomes broadly to the scientific community and public at large.
