VAST Center: Viromes Across Space(s) and Time

Stanford University, Stanford CA

Investigators

Abstract

ABSTRACT Compared to the human microbiome work focused on bacteria, characterization of the human virome is still nascent. This is primarily a result of the inherent challenges posed by the viruses, since viruses in human bodies are highly diverse, small, and generally rare in the context of the microbiome. To address these gaps in knowledge, our Viromes Across Spaces and Time (VAST) Center will contain a dedicated Biospecimens Analysis Core (BAC), which will be responsible for extracting, processing, and sequencing the comprehensive virome and microbiome profiles for all cohorts in our Virome Characterization Center (VCC). The next-generation sequencing (NGS), molecular, and functional data can then be used by our VAST group, the other VCCs, and the broader scientific community, to improve our understanding of the human virome. We will accomplish the goals of the BAC across 3 main aims and several sub-aims. First, we will (Aim 1) optimize virome enrichment, quantification, and spatial mapping methods, including a pan-virome panel of almost all currently known viruses, multiple-displacement amplification (MDA) for low biomass samples, and viral-like particles (VLP) enrichment. Secondly, we will (Aim 2) generate metagenomic and metatranscriptomic sequences from >15,000 samples and examine sub-cellular, spatial localization of viruses in skin samples, which is essential for improved understanding of viral localization in tissues. Finally, we will (Aim 3) sequence and annotate long read viromes from 1,000 high-complexity, longitudinal samples. Equipped with state-of-art sequencing and imaging technology, our BAC has an unprecedented opportunity to detect both DNA and RNA viruses in the human body, determine their stability (and dynamics) longitudinally, map their location in cells, and discover novel viruses from the viral ‘dark matter’. Our aims will (1) capture viral diversity from different anatomical regions, which likely harbor unique viromes and varied host-environment interactions, (2) identify novel viruses, thereby enriching our understanding of viral evolution and novel alleles, and (3) track low-abundance species, which are sometimes pervasive across the body. These data can also improve measures of viral evolution by curating short-read and long-read data from these cohorts and tracking their changes over time, which will map host-microbial interactions and tropism at cellular and even sub-cellular (50nm) resolution. Analyzing these high volumes of diverse data from global and longitudinal cohorts will enable comprehensive mapping of viral dynamics and biology. Moreover, the generation of high-quality, comprehensive data on the virome of various tissues and samples will contribute significantly to our understanding of the human virome, host interactions, and implications in health and disease.