UAB Center for Precision Animal Modeling (CPAM)

University Of Alabama At Birmingham, Birmingham AL

Investigators

Linked publications, trials & patents

Abstract

ABSTRACT (OVERALL SECTION) The identification of genetic variants associated with human diseases is accelerating, thanks to advances in technology and reduced costs of next-generation sequencing. Distinguishing between pathogenic and benign variants poses a significant challenge, necessitating robust informatics tools complemented with experimental validation. These tools must analyze extensive amounts of data and present it in a comprehensive and accessible format for expert evaluation and prioritization of the variants based on likely clinical significance. These tools must help select optimal model systems in which to engineer the variant to mimic human disease, to study disease mechanisms, identify and test therapeutics, and to develop diagnostic tools and clinical care strategies. To tackle this complex set of issues, we established the Center for Precision Animal Modeling (CPAM1.0) in 2020. CPAM’s multidisciplinary team encompasses expertise in clinical care, disease diagnostics, genetics, computational and data sciences, artificial intelligence and machine learning, genome engineering, disease modeling, and therapeutic screening. This network of expertise forms a well-integrated and efficient CPAM analysis platform through which community-based nominations undergo systematic evaluation using established criteria, ensuring that selected variants represent both scientific merit and potential patient benefit. CPAM’s Preclinical/Co-clinical Section (PCS) serves as the liaison for incoming nominations and manages comprehensive patient clinical data collection, ensuring secure integration of medical records, genomic information, and treatment histories along with robust patient protection policies. The PCS received 169 submissions over the past four years, highlighting the demand. Each nominated variant undergoes thorough analysis by our Bioinformatics Section (BIS), with reports presented to the Steering Committee (SC) for evaluation, selection and prioritization of variants for further modeling. For projects that CPAM accepts for disease modeling, the Coordination Section (CS) initiates collaborations and the BIS employs AI approaches to identify therapeutic strategies. The Disease Modeling Unit (DMU) develops patient variant human cell and animal models across multiple species. These models are analyzed in parallel with clinical investigation enabling direct comparisons to help ensure that CPAM animal models effectively predict treatment outcomes and accelerate therapeutic development. Concurrently, the Resource and Service Section (RSS) and the BIS develop functional assays to assess variant pathogenicity and test prioritized drugs. After establishing the animal model, the RSS conducts quality control, cryopreserves the line, and distributes it to collaborators and repositories. The DMU evaluates phenotypes, and interfaces with the BIS, PCS and a Phenotype Validation and Clinical Curation Committee to assess human disease relevance. Finally, the BIS compiles all data into a final Patient Variant Report and the PCS returns results to the nominator. Ultimately, CPAM has a pivotal role in driving the translation of genomic discoveries into tailored therapies that can significantly improve patient outcomes.