Language

English

Publication Date

7-1-2025

Journal

Nature Biotechnology

DOI

10.1038/s41587-024-02382-1

PMID

39455800

PMCID

PMC12022141

PubMedCentral® Posted Date

10-25-2024

PubMedCentral® Full Text Version

Post-print

Abstract

Research and medical genomics require comprehensive, scalable methods for the discovery of novel disease targets, evolutionary drivers and genetic markers with clinical significance. This necessitates a framework to identify all types of variants independent of their size or location. Here we present DRAGEN, which uses multigenome mapping with pangenome references, hardware acceleration and machine learning-based variant detection to provide insights into individual genomes, with ~30 min of computation time from raw reads to variant detection. DRAGEN outperforms current state-of-the-art methods in speed and accuracy across all variant types (single-nucleotide variations, insertions or deletions, short tandem repeats, structural variations and copy number variations) and incorporates specialized methods for analysis of medically relevant genes. We demonstrate the performance of DRAGEN across 3,202 whole-genome sequencing datasets by generating fully genotyped multisample variant call format files and demonstrate its scalability, accuracy and innovation to further advance the integration of comprehensive genomics. Overall, DRAGEN marks a major milestone in sequencing data analysis and will provide insights across various diseases, including Mendelian and rare diseases, with a highly comprehensive and scalable platform.

Keywords

Humans, Genome, Human, Genomics, Software, Genetic Variation, Whole Genome Sequencing, DNA Copy Number Variations, Polymorphism, Single Nucleotide, Machine Learning, Software, Genomics, Computational biology and bioinformatics

Published Open-Access

yes

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