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The Administrative Core provides structure, oversight, and enables the activities of the Alzheimer Gut Microbiome Project. It ensures that all Projects and Cores are integrated, and function effectively and efficiently.
The core oversees the integration of data developed by collaborators, coordinates the interactions with the National Centralized Repository for Alzheimer’s Disease and Related Dementias (NCRAD), which serves as the repository of collected biospecimens for the project which are made available to collaborators and the greater research community.
This Core is co-led by Drs. Rima Kaddurah-Daouk (Duke University), Rob Knight (UC San Diego), and Sarkis Mazmanian (CalTech), who bring considerable leadership experience and complementary scientific expertise to AGMP.
- Dr. Kaddurah-Daouk serves as the contact PI and brings the experience of having successfully led four large NIH-funded consortia and is a pioneer in the application of metabolomics in neuropsychiatric diseases, including defining a role for the gut microbiome in AD.
- Dr. Knight runs the American Gut Project/The Microsetta Initiative and developed microbiome technologies widely used in the field.
- Dr. Mazmanian discovered a role for the gut microbiome in the pathogenesis of neuropsychiatric diseases.
Omics & Technology
The Omics & Technology Core acts as a portal that interconnects all parts of the project and provides high-quality genomics, metabolomics, and imaging data, that is integrated with clinical and phenotyping information.
This core works closely with NCRAD (ncrad.org), implementing standardized procedures for the collection of samples across the Alzheimer Centers, coordinating shipments to our hubs for sample analysis, and enabling tracking of samples and data. This core also works closely with the bioinformatics core to ensure gold-standard data management and to enable comprehensive data mining for the whole scientific community.
The core conducts state of the art metagenomics (analysis of collected samples to profile the entire microbial community inhabiting the gut), metabolomics (analysis of blood and feces, to profile the host and gut-microbiota metabolomes), and quantitative magnetic resonance imaging of the brain, which contributes an additional layer to the phenotyping of the study participants.
Computational & Systems Biology
The Computational & Systems Biology Core provides access to advanced data analysis algorithms and pipelines for the entire project. High-quality preprocessed data is seamlessly integrated from the Omics & Technology Core. Our analysis pipelines perform all major steps of data analysis, including outlier detection, differential analysis, pathway analysis, and advanced network methods. We are developing additional methods specifically tailored for multi-compartment omics data in this project (e.g., from blood, gut, and brain). Such novel methods for integrated multi-omics and multi-compartment data provide a unique readout of Alzheimer’s Disease pathology, allowing us to unlock the full potential behind these heterogeneous datasets.
This core develops computational models for human-microbe co-metabolism, which allows in silico simulations of external influences, such as diet, at a physiological scale.
A second, major focus of the core is on the development and application of a microbiome-centric bioinformatic knowledge base (an “atlas”). To this end, we are constructing a Neoj4-based network database integrating various heterogeneous information, including results from metabolomics GWAS, eQTL studies, Alzheimer-phenotype related association studies (e.g., metabolomics biomarkers of AD endophenotypes), microbiome-metabolome associations, etc. The atlas will allow us to answer complex research questions, such as finding the connections between a given set of metabolites, genes, metabolic pathways, GWAS hits, and AD endophenotypes in one single query.