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Tracing the evolution of sequencing into the era of genomic medicine

Nature Reviews Genetics volume 26, pages 719–734 (2025)Cite this article

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Abstract

Accelerated discovery in biomedical science is typically punctuated by technological advances, and the past decade has been exemplary regarding breakthroughs in our genomic understanding of human biology in health and disease. This phenomenon was facilitated by the availability of a human genome reference sequence and the development and continuous improvement of next-generation and single-molecule sequencing technologies, accompanied by advances in computational analytics. These fundamental tools have driven the emergence of innovative methods that capture different aspects of human cell biology, with exquisite detail genome wide, in a sequence-based readout. The resulting expansion of knowledge has poised these approaches for clinical adoption, fulfilling the original intention of decoding the human genome and ushering in the era of genomic medicine.

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Fig. 1: Milestones in sequencing technology advances and projects.
Fig. 2: Human sequence variation types detected by NGS.
Fig. 3: Long-read, single-molecule sequencing platforms.
Fig. 4: From bulk to single-cell and spatial sequencing.
Fig. 5: Genomic medicine workflows in the paediatric and adult settings.

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Acknowledgements

The authors acknowledge K. Miller and A. Miller for their review of the manuscript, M. Artomov for input regarding polygenic risk scoring and D. Koboldt for insights on ClinGen, ClinVar and Matchmaker Exchange.

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  1. Rasmussen Institute for Genomic Medicine, Nationwide Children’s Hospital, Columbus, OH, USA

    Elaine R. Mardis & Richard K. Wilson

  2. Department of Paediatrics, The Ohio State University College of Medicine, Columbus, OH, USA

    Elaine R. Mardis & Richard K. Wilson

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  1. Elaine R. Mardis
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  2. Richard K. Wilson
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Related links

ClinGen: https://clinicalgenome.org/

ClinVar: https://www.ncbi.nlm.nih.gov/clinvar/intro/

Integrative Genomics Viewer: https://igv.org/

Matchmaker Exchange: https://www.matchmakerexchange.org/

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Mardis, E.R., Wilson, R.K. Tracing the evolution of sequencing into the era of genomic medicine. Nat Rev Genet 26, 719–734 (2025). https://doi.org/10.1038/s41576-025-00884-5

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