BUADRC GMP Core
Project Title: Genetics & Molecular Profiling Core
Project Goals: The new Genetics & Molecular Profiling (GMP) Core is building on previous work of genetics and molecular characterization of BU ADRC participants and other cohorts that has led to numerous important discoveries and greatly increased our understanding of mechanisms and biological pathways leading to AD. The GMP serves as a centralized resource for the organization and analysis of genetic data within the ADRC and, affiliated projects by providing an infrastructure needed to coordinate molecular research efforts that will lead to a better understanding of genotype-phenotype relationships for dementia and related endophenotypes.
Project Website: https://www.bu.edu/alzresearch/genetics-molecular-profiling-core/
Project Aims
Aim 1. Expand and provide additional infrastructure for a repository for genetic and ’omics materials from blood and brain specimens. We will continue and augment the BU ADRC repository for genetic material housed in the BU Molecular Genetics Core Facility. These samples will be tracked by a laboratory information management system (LIMS) database with direct linkage to the DMS Core that contains phenotype, biomarker and, in some instances, neuropathological, information for the same subjects. The biorepository will also provide specimens to investigators in response to biomaterial requests approved by the ADRC Executive Committee.
Aim 2. Generate genetic, genomic, transcriptomic, methylomic, and lipidomic data. We will continue to obtain large-scale quality-controlled genome-wide association study (GWAS) and whole genome sequence (WGS) and whole exome sequence (WES) data generated by the Alzheimer Disease Genetics Consortium (ADGC) and Alzheimer Disease Sequencing Project (ADSP), respectively, from blood and brain samples obtained from ADRC participants. In addition, we will generate and develop analysis pipelines for transcriptomic, epigenomic, and lipidomic data derived from blood and brain specimens obtained by ADRC Cores or other sanctioned research projects. Molecular characterization of specimens from ADRC subjects with various clinical and neuropathological AD/ADRD diagnoses will provide investigators with a backbone of data for studies correlating genotypes and phenotypes, as well as for more targeted research informed by genetic background. The GMP Core will also perform or facilitate acquisition of other types of genomic data (e.g., microRNA sequence, single nuclei RNA sequence) from ADRC specimens for sponsored research projects.
Aim 3. Maintain an Integrated Genetic and ‘omic Database. We will maintain a database that includes all genetic and ‘omic data generated from BU ADRC samples and is linked to databases in the Clinical, Neuropathology and Biomarker Cores. This will provide comprehensive up-to-date information on all genetic data available and will support studies within and affiliated with the ADRC. We will also maintain working libraries of extant genetic and ‘omic data; these data will be available with proper permissions as a resource for genetic analyses with guidance from the core investigators. The GMP Core will also facilitate access to an extensive set of genetic and genomic data from extant datasets that are available to the Core investigators including individual level and/or summarized data from the ADGC, ADSP, ADNI, AMP-AD, and UK Biobank.
Aim 4. Provide Study Design and Analytical Support. GMP Core investigators will provide support, training and education in study design, and statistical genetic and bioinformatic analysis for ADRC-affiliated studies. The Core will also assist investigators of ADRC-affiliated studies in gaining access to storage and compute nodes on the BU Shared Computing Cluster that is needed for analysis of large-scale genomic data.