UAB Center for Precision Animal Modeling (CPAM) - Bioinformatics Section

University Of Alabama At Birmingham, Birmingham AL

Investigators

Linked publications, trials & patents

Abstract

ABSTRACT (BIOINFORMATICS SECTION) Advances in sequencing and analytical technologies have accelerated the identification of genetic variations associated with disease. However, distinguishing pathogenic variants from benign ones and defining the functional impact of variants remain significant challenges, often requiring application of robust computational tools and experimental validation. Even when they are part of undiagnosed disease programs, patients are often left with non-actionable variants or variants of uncertain significance. To address these challenges, the UAB Center for Precision Animal Modeling (CPAM1.0) was established in 2020 with the goal of efficiently analyzing and modeling variants, supporting diagnoses, variant impact assessment, and therapeutic target identification. The Bioinformatics Section (BIS) is a cornerstone of CPAM, driving efficiency and innovation through application of computational tools, methods, and expertise, supporting all phases of the CPAM process. The BIS advances knowledge generation by facilitating allele review and selection, variant impact prediction, cross-species functional assessment, and drug repurposing strategies. It enhances CPAM capabilities by streamlining data analyses, supporting data collection and curation, and providing support for cataloguing animal strains, cell lines, biomaterials, and protocols. BIS also assists in tracking and monitoring CPAM’s overall impact. In CPAM1.0, the BIS established the computational framework now central to the Center’s operations. This included developing the CPAM website, the Rosalution analytical portal, and a secure data repository to streamline data integration, sharing, and collaboration. In CPAM1.0 the BIS also created novel computational biology and data science based analytical tools and methods for variant classification, cross-species genotype- phenotype analysis, tissue-specific assessments, and drug repurposing predictions. These resources supported variant prioritization and nomination decision-making, aided in model generation and validation, and maximized the impact of CPAM through real-time data sharing, curation, analysis, and collaboration. In CPAM2.0, the BIS will develop and implement additional tools and capabilities to meet evolving needs. The BIS will integrate innovative machine learning, generative AI, and computational biology methods to predict phenotypic outcomes, predict and streamline selection of optimal model organisms, perform precise patient- model phenotypic comparisons, integrate tools for phenotype assessment, and identify therapeutic targets and repurposing candidates. It will expand the Rosalution portal to incorporate additional variant, gene, transcript, and phenotype annotations and expand CPAM cataloguing of animal strains, cell lines, biomaterials, and protocols, fostering collaboration and enriching resources for the research community. Ultimately, the BIS is an integral part of CPAM and plays a crucial role in advancing our understanding of genetic variants and their clinical implications.