Project Summary The University of California San Diego (UCSD) Microbiome and Metagenomics Center (MMC) as part of the Nutrition for Precision Health (NPH) consortium will provide rapid, robust stool sample processing, high-quality metagenomic and metatranscriptomic data generation, and best-in-class bioinformatic analysis. We will optimize our protocols for DNA and RNA extraction from stool, metagenomic and metatranscriptomic library preparation, sequencing, and bioinformatics for ultra-high resolution taxonomic and functional profiling of the microbiome, including bacteria, archaea, eukaryotes, and viruses. We will offer analytical services and expertise on study design, sample collection, statistics, artificial intelligence, and host-microbe data interpretation to support other NPH centers and develop standard operation procedures with the Research Coordinating Center (RCC). Our team has developed uniquely innovative approaches to provide metagenomic and metatranscriptomic data at a cost that facilitates application to all 17,500 samples provided by the BioBank, with robust quality control to ensure high-quality raw and processed data products. We are also able to provide absolute quantification of microbial load through our recent innovation in synthetic DNA ‘spike-ins', which also facilitates rigorous assessment of contamination and extraction efficiency. Beyond bringing cutting edge technology that we have developed to the consortium, we also propose 3 Pilot Projects: (i) long-read data assembly; (ii) multiplexed metaproteomics; and (iii) automated stool sample collection and processing, so as to improve the taxonomic and functional resolution of profiling and improve biomarker detection sensitivity using dense timeseries. Importantly, our team is also optimally positioned to develop community consensus for the analysis strategies agreed on during the planning year, as well as to address the challenges of integrating microbiome data into the NPH consortium, due to our: existing high-throughput sample processing, sequencing, and data analysis cores; tight integration among disciplinary groups; access to supercomputing infrastructure; data visualization expertise; and tight coordination with an international braintrust of scientists who have been selected based on their complementary expertise in different areas of microbiome and precision nutrition research. This center will also benefit from cross-campus institutional commitment to provide 4 undergraduate, 5 postgraduate, and 6 postdoctoral fellowships, enabling faculty engagement and the development of innovative technologies and algorithms to advance NPH consortium goals. Additionally, our existing community outreach experiences can further support the NPH consortium’s goal to provide respectful, accessible and engaging feedback to the participants. Essential to the success of the MMC is the 35% time-commitment of the PI who has an outstanding track record in leading similar scale efforts. As a key part of the NPH consortium, we aim to democratize microbiome data by reducing cost, time, and computational requirements and coordination of multidisciplinary expertise required for data analyses and interpretation to achieve the ambitious goals of precision nutrition.

Project Narrative The proposed Microbiome and Metagenomics Center is relevant to human health because we anticipate results can be used by the Nutrition for Precision Health Consortium to understand the relationship between the microbiome, nutrition, and human health. Data and technologies developed will be widely available to the community to promote further scientific advances. The Center is relevant to NIH and NIDDK’s mission because it seeks to produce high quality metagenomic and metatranscriptomic data that will help determine how nutrition and the microbiome can be used to improve people’s health and quality of life.