PROJECT SUMMARY: Functional Genomics and Microbiome Core (Biomedical Research Core) The Functional Genomics and Microbiome (FGM) Core of the Texas Medical Center Digestive Disease Center (DDC) supports the DDC’s mission and enhances research programs in the theme of infection and injury affecting the intestine and liver. This core enhances the Center’s scope in response to DDC user demand and the center’s commitment to the importance of the microbiome:mammalian interface in gastrointestinal and liver biology. The FGM Core strives to bring together the microbial and mammalian biology underpinning molecular mechanisms of digestive diseases. It accomplishes this purpose via multi-omics approaches based on large- scale data generation and deep analytics of microbial and mammalian cell populations. The FGM Core is a comprehensive resource with services including consultation on experimental design and specimen processing, robust data generation and analysis pipelines, bioinformatics strategies, and biostatistical support. We have created a fully integrated genomic and multi-omic analysis platform for investigators studying digestive diseases that is highly used by DDC members (25 of 62 Full Member usage, >680 service requests, and 83 resulting publications during the present funding cycle). The FGM Core provides DDC members with instrumentation and expertise to facilitate microbial and mammalian genomics, transcriptomics, metabolomics, and protein analytics applied to gastrointestinal diseases characterized by infection, injury, or altered metabolic states. DDC members’ research programs are nurtured by this Core’s ability to bridge microbiome science and mammalian biology and to provide multi-tiered services at the levels of genes and effectors (proteins and metabolites). This Core uses tools and services, such as highly parallel nucleic acid sequencing, mass spectrometry-guided metabolomics and proteomics, and supercomputer- guided bioinformatics and molecular modeling. The FGM Core serves as a platform for gastrointestinal and hepatic systems biology by enabling studies of mammalian and microbial gene expression profiles, intracellular signaling pathways, and cell:cell communication channels. The FGM Core offers highly innovative services that are both institutionally shared and DDC member-exclusive. The Core leverages for DDC members (at subsidized rates) the capital-intensive resources (chiefly instrumentation) within the institutional microbiome and mammalian functional genomics facilities to accomplish its Aims 1 (to elucidate mammalian gene expression and epigenomics in DD) and Aim 2 (to generate functional insights into microbiome/virome using metagenomic approaches). The liquid chromatography-mass spectrometry-based metabolomic and proteomic services (Aim 3) coupled with advanced bioinformatics (Aim 4) are exclusively operated for DDC members.