AoUPRS: A cost-effective and versatile PRS calculator for the All of Us Program

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Publicado en:BMC Genomics vol. 26 (2025), p. 1
Autor principal: Khattab, Ahmed
Otros Autores: Shang-Fu, Chen, Wineinger, Nathan, Torkamani, Ali
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Springer Nature B.V.
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024 7 |a 10.1186/s12864-025-11693-9  |2 doi 
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100 1 |a Khattab, Ahmed 
245 1 |a AoUPRS: A cost-effective and versatile PRS calculator for the <i>All of Us</i> Program 
260 |b Springer Nature B.V.  |c 2025 
513 |a Journal Article 
520 3 |a BackgroundThe All of Us (AoU) Research Program provides a comprehensive genomic dataset to accelerate health research and medical breakthroughs. Despite its potential, researchers face significant challenges, including high costs and inefficiencies associated with data extraction and analysis. AoUPRS addresses these challenges by offering a versatile and cost-effective tool for calculating polygenic risk scores (PRS), enabling both experienced and novice researchers to leverage the AoU dataset for large-scale genomic discoveries.MethodsWe evaluated three PRS models from the PGS Catalog (coronary artery disease, atrial fibrillation, and type 2 diabetes) using two distinct approaches in the Hail framework: MatrixTable (MT), a dense representation, and Variant Dataset (VDS), a sparse representation optimized for large-scale genomic data. Computational cost, resource usage, and processing time were compared. To assess the similarity of PRS performance between these two approaches, we compared odds ratios (ORs) and area under the curve (AUC). Lin’s concordance correlation coefficient (CCC) was also computed to quantify agreement between PRS scores generated by MT and VDS.ResultsThe VDS approach reduced computational costs by up to 99.51% (e.g., from $32 to $0.036 for a 51-SNP score) while maintaining PRS estimates that were highly similar to those obtained using the MT approach. Across all three PRS models, AUC comparisons showed minimal differences between MT and VDS, indicating that both approaches yield consistent PRS performance. Agreement between PRS scores calculated by both approaches was further supported by Lin’s CCC values ranging from 0.9199 to 0.9944, confirming strong concordance. Empirical cumulative distribution function (ECDF) plots further illustrated the near-identical distribution of PRS values across methods.ConclusionsAoUPRS enables efficient and cost-effective PRS computation within AoU, providing substantial cost savings while maintaining highly consistent PRS estimates. These findings support the use of AoUPRS for large-scale genomic risk assessment, making the AoU dataset more accessible and practical for diverse research applications. The tool’s open-source availability on GitHub, coupled with detailed documentation and tutorials, ensures accessibility and ease of use for the scientific community. 
653 |a Diabetes mellitus (non-insulin dependent) 
653 |a Accessibility 
653 |a Coronary artery disease 
653 |a Datasets 
653 |a Medical research 
653 |a Regression analysis 
653 |a Genomics 
653 |a Heart diseases 
653 |a Quality control 
653 |a Computer applications 
653 |a Risk assessment 
653 |a Correlation coefficients 
653 |a Correlation coefficient 
653 |a Representations 
653 |a Cost effectiveness 
653 |a Efficiency 
653 |a Electronic health records 
653 |a Distribution functions 
653 |a Cost reduction 
653 |a Cardiovascular disease 
653 |a Estimates 
653 |a Computing costs 
653 |a Cost analysis 
653 |a Single-nucleotide polymorphism 
653 |a Cost control 
653 |a Social 
700 1 |a Shang-Fu, Chen 
700 1 |a Wineinger, Nathan 
700 1 |a Torkamani, Ali 
773 0 |t BMC Genomics  |g vol. 26 (2025), p. 1 
786 0 |d ProQuest  |t Health & Medical Collection 
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