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Detecting hierarchical genome folding with network modularity

Nature Methods volume 15, pages 119122 (2018) | Download Citation

Abstract

Mammalian genomes are folded in a hierarchy of compartments, topologically associating domains (TADs), subTADs and looping interactions. Here, we describe 3DNetMod, a graph theory-based method for sensitive and accurate detection of chromatin domains across length scales in Hi-C data. We identify nested, partially overlapping TADs and subTADs genome wide by optimizing network modularity and varying a single resolution parameter. 3DNetMod can be applied broadly to understand genome reconfiguration in development and disease.

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References

  1. 1.

    & Nat. Rev. Neurosci. 10, 186–198 (2009).

  2. 2.

    & Proc. Natl. Acad. Sci. USA 99, 7821–7826 (2002).

  3. 3.

    , , , & Nat. Rev. Genet. 8, 104–115 (2007).

  4. 4.

    , & Nat. Rev. Genet. 14, 390–403 (2013).

  5. 5.

    et al. Science 326, 289–293 (2009).

  6. 6.

    et al. Cell 153, 1281–1295 (2013).

  7. 7.

    et al. Cell 159, 1665–1680 (2014).

  8. 8.

    et al. Nature 485, 376–380 (2012).

  9. 9.

    et al. Nature 485, 381–385 (2012).

  10. 10.

    et al. Cell 148, 458–472 (2012).

  11. 11.

    & Nucleic Acids Res. 45, 2994–3005 (2017).

  12. 12.

    et al. Nat. Methods 14, 679–685 (2017).

  13. 13.

    Proc. Natl. Acad. Sci. USA 103, 8577–8582 (2006).

  14. 14.

    , , & J. Stat. Mech. Theory. E. 2008, P10008 (2008).

  15. 15.

    Nat. Phys. 8, 25–31 (2012).

  16. 16.

    et al. Nature 538, 523–527 (2016).

  17. 17.

    & Neuroimage 56, 2068–2079 (2011).

  18. 18.

    , & Phys. Rev. E 84, 036103 (2011).

  19. 19.

    & Bioinformatics 32, 1601–1609 (2016).

  20. 20.

    et al. Nat. Genet. 49, 1239–1250 (2017).

  21. 21.

    et al. Genome Biol. 16, 259 (2015).

  22. 22.

    et al. Nat. Methods 9, 999–1003 (2012).

  23. 23.

    , & Phys. Rev. E 81, 046106 (2010).

  24. 24.

    , , & SIAM Rev. 53, 526–543 (2011).

  25. 25.

    & J. Classif. 2, 193–218 (1985).

  26. 26.

    , & Proc. Natl. Acad. Sci. USA 109, 18661–18668 (2012).

  27. 27.

    , , & PLoS Comput. Biol. 10, e1003712 (2014).

  28. 28.

    & Science 296, 910–913 (2002).

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Acknowledgements

J.E.P.-C. is a New York Stem Cell Foundation (NYSCF) Robertson Investigator and an Alfred P. Sloan Foundation Fellow. This work was funded by The New York Stem Cell Foundation (J.E.P.-C.), the Alfred P. Sloan Foundation (J.E.P.-C.), the NIH Director's New Innovator Award (1DP2MH11024701; J.E.P.-C.), a 4D Nucleome Common Fund grant (1U01HL12999801; J.E.P.-C.) and a joint NSF-NIGMS grant to support research at the interface of the biological and mathematical sciences (1562665; J.E.P.-C.). This material is based upon work supported by the National Science Foundation Graduate Research Fellowship under DGE-1321851 (H.N.). D.S.B. would also like to acknowledge support from the John D. and Catherine T. MacArthur Foundation.

Author information

Author notes

    • Heidi K Norton
    •  & Daniel J Emerson

    These authors contributed equally to this work.

Affiliations

  1. Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Heidi K Norton
    • , Daniel J Emerson
    • , Harvey Huang
    • , Jesi Kim
    • , Katelyn R Titus
    • , Shi Gu
    • , Danielle S Bassett
    •  & Jennifer E Phillips-Cremins
  2. Brain Behavior Laboratory, Department of Psychiatry, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Shi Gu
  3. Electrical and Systems Engineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Danielle S Bassett
  4. Epigenetics Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Jennifer E Phillips-Cremins
  5. Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Jennifer E Phillips-Cremins

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Contributions

J.E.P.-C., D.S.B. and H.K.N. conceived of the study. H.K.N., D.J.E., S.G., H.H., K.R.T. and J.K. implemented the computational pipeline. J.E.P.-C., H.K.N., D.J.E. and D.S.B. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Jennifer E Phillips-Cremins.

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DOI

https://doi.org/10.1038/nmeth.4560

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