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Automated sequence-based annotation and interpretation of the human genome

A machine-learning model produces summarized sequence representations of genomic regulatory activity, and provides a functional view of regulatory DNA variation in the human genome, with the aim of better understanding the role of sequence variation in health and disease.

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Fig. 1: Conceptual overview of the Sei framework.


  1. Roadmap Epigenomics Consortium. Nature 518, 317–330 (2015).

    Article  Google Scholar 

  2. ENCODE Project Consortium. Nature 583, 699–710 (2020).

    Article  Google Scholar 

  3. Zheng, R. et al. Nucleic Acids Res. 47, D729–D735 (2019).

    CAS  Article  Google Scholar 

  4. Meuleman, W. et al. Nature 584, 244–251 (2020).

    CAS  Article  Google Scholar 

  5. Chen, K. M., Wong, A. K., Troyanskaya, O. G. & Zhou, J. Nat. Genet. (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  6. Zentner, G. E. & Henikoff, S. Nat. Rev. Genet. 15, 814–827 (2014).

    CAS  Article  Google Scholar 

  7. Avsec, Ž. et al. Nat. Genet. 53, 354–366 (2021).

    CAS  Article  Google Scholar 

  8. Avsec, Ž. et al. Nat. Methods 18, 1196–1203 (2021).

    CAS  Article  Google Scholar 

  9. Zhou, J. & Troyanskaya, O. G. Nat. Methods 12, 931–934 (2015).

    CAS  Article  Google Scholar 

  10. Zhou, J. et al. Nat. Genet. 50, 1171–1179 (2018).

    CAS  Article  Google Scholar 

  11. Janssens, J. et al. Nature 601, 630–636 (2022).

    CAS  Article  Google Scholar 

  12. Stenson, P. D. et al. Hum. Genet. 139, 1197–1207 (2020).

    Article  Google Scholar 

  13. Maslova, A. et al. Proc. Natl Acad. Sci. USA 117, 25655–25666 (2020).

    CAS  Article  Google Scholar 

  14. Alipanahi, B., Delong, A., Weirauch, M. T. & Frey, B. J. Nat. Biotechnol. 33, 831–838 (2015).

    CAS  Article  Google Scholar 

  15. Ching, T. et al. J. R. Soc. Interface 15, 20170387 (2018).

    Article  Google Scholar 

  16. Zhou, J. Nat. Genet. 54, 725–734 (2022).

    CAS  Article  Google Scholar 

Download references

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Correspondence to Anshul Kundaje or Wouter Meuleman.

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Competing interests

A.K. is scientific co-founder of Ravel Biotechnology, is on the scientific advisory board of PatchBio, SerImmune, AINovo, TensorBio and OpenTargets, is a consultant with Illumina and owns shares in DeepGenomics, Immuni and Freenome. W.M. has no competing interests.

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Kundaje, A., Meuleman, W. Automated sequence-based annotation and interpretation of the human genome. Nat Genet 54, 916–917 (2022).

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