DoAggregate: a pipeline for aggregation testing for rare-variants on a gene and pathway level
(2025) Abstracts from the 58th European Society of Human Genetics (ESHG) Conference: Hybrid Posters — Location: Milan, Italy (24.May.2025)
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- Background: Aggregation tests address the limitations inherent to the analysis of rare variants in cohort studies by allowing for the combination of multiple genetic markers within a genomic region. However, choosing the appropriate statistical test remains a challenge, as existing tools often fail to provide a comprehensive solution that encompasses automatic data processing, gene-level testing, and exploration of broader genetic regions such as pathways. Material and Methods: To address these questions, we developed DoAggregate, an innovative, scalable pipeline designed for high-performance computing environments. DoAggregate processes lists of annotated genetic variants in TSV or GVCF formats, supporting tasks ranging from data filtering through pathway analysis to identification of regions of interest, including genes and pathways. It incorporates Excalibur, an ensemble method combining 36 aggregation tests, enhancing analysis by presenting detailed results in Excel format with annotations and plots for nuanced interpretation. The pipeline supports parallelization via Slurm, requires minimal input, and provides extensive resources for data preparation and analysis. Results: DoAggregate is a comprehensive pipeline for aggregation testing that facilitates in-depth exploration of genetic regions across genomes and exomes. By combining detailed annotations, robust statistical frameworks and user-friendly outputs, DoAggregate improves the interpretation of genomic data. Conclusion: Our results demonstrate its effectiveness in uncovering disease-related genetic architectures, accelerating biomarker discovery and paving the way for new therapeutic targets, making it an indispensable tool for genomic researchers.
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Boutry, S., van Marcke de Lummen, C. J., Limaye, N., Smits, G., Brouillard, P., De Bortoli, M., Pairet, E., Saadat Varnosfaderanii, A., Helaers, R., Fellay, J., Lenaerts, T., & Vikkula, M. (2025). DoAggregate: a pipeline for aggregation testing for rare-variants on a gene and pathway level. European Journal of Human Genetics, 33(S1), 508-1220. https://doi.org/10.1038/s41431-025-01935-5 (Original work published 2025)