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The mutation significance cutoff: gene-level thresholds for variant predictions

Nature Methods volume 13, pages 109110 (2016) | Download Citation

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References

  1. 1.

    et al. Nat. Methods 7, 248–249 (2010).

  2. 2.

    , & Nat. Protoc. 4, 1073–1081 (2009).

  3. 3.

    et al. Nat. Genet. 46, 310–315 (2014).

  4. 4.

    , , , & PLoS Genet. 9, e1003709 (2013).

  5. 5.

    et al. Nat. Genet. 46, 944–950 (2014).

  6. 6.

    et al. Proc. Natl. Acad. Sci. USA 112, 13615–13620 (2015).

  7. 7.

    et al. Hum. Genet. 133, 1–9 (2014).

  8. 8.

    et al. Nucleic Acids Res. 42, D980–D985 (2014).

  9. 9.

    et al. Nature 526, 68–74 (2015).

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Acknowledgements

We thank M. Kircher for information about the CADD method and D.B. Goldstein for gene-level metrics insights. We thank Y. Nemirovskaya, E. Anderson, M. Woollett and D. Papandrea for administrative support. Y.I. was supported in part by grant no. UL1 TR000043 from the National Center for Advancing Translational Sciences (NCATS), US National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program. This study was supported by the Rockefeller University and the St. Giles Foundation.

Author information

Author notes

    • Shen-Ying Zhang
    • , Laurent Abel
    •  & Jean-Laurent Casanova

    These authors contributed equally to this work.

Affiliations

  1. St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, The Rockefeller University, New York, New York, USA.

    • Yuval Itan
    • , Lei Shang
    • , Bertrand Boisson
    • , Michael J Ciancanelli
    • , Janet G Markle
    • , Ruben Martinez-Barricarte
    • , Ishaan Shah
    • , Shen-Ying Zhang
    • , Laurent Abel
    •  & Jean-Laurent Casanova
  2. Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Paris, France.

    • Bertrand Boisson
    • , Shen-Ying Zhang
    • , Laurent Abel
    •  & Jean-Laurent Casanova
  3. Paris Descartes University, Imagine Institute, Paris, France.

    • Bertrand Boisson
    • , Shen-Ying Zhang
    • , Laurent Abel
    •  & Jean-Laurent Casanova
  4. Neurogenetics Laboratory, Department of Neurosciences, University of California, San Diego, San Diego, California, USA.

    • Eric Scott
    •  & Joseph Gleeson
  5. Institute of Medical Genetics, School of Medicine, Cardiff University, Cardiff, UK.

    • Peter D Stenson
    •  & David N Cooper
  6. Howard Hughes Medical Institute, New York, New York, USA.

    • Joseph Gleeson
    •  & Jean-Laurent Casanova
  7. Human Evolutionary Genetics Unit, Institut Pasteur, Paris, France.

    • Lluis Quintana-Murci
  8. Centre National de la Recherche Scientifique, URA 3012, Paris, France.

    • Lluis Quintana-Murci
  9. Pediatric Immunology-Hematology Unit, Necker Hospital for Sick Children, Paris, France.

    • Jean-Laurent Casanova

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Competing interests

D.N.C. and P.D.S. are in receipt of funding from Qiagen through a license agreement with Cardiff University. The other authors declare that they have no competing financial interests.

Corresponding author

Correspondence to Yuval Itan.

Integrated supplementary information

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–6, Supplementary Note and Supplementary Methods

Excel files

  1. 1.

    Supplementary Table 1

    A summary of the CADD-based 99% CI MSC protein-coding human genes.

  2. 2.

    Supplementary Table 2

    A summary of the CADD-based 95% CI MSC protein-coding human genes.

  3. 3.

    Supplementary Table 3

    A summary of the CADD-based 90% CI MSC protein-coding human genes.

  4. 4.

    Supplementary Table 4

    A summary of the PolyPhen-2-based 99% CI MSC protein-coding human genes.

  5. 5.

    Supplementary Table 5

    A summary of the PolyPhen-2-based 95% CI MSC protein-coding human genes.

  6. 6.

    Supplementary Table 6

    A summary of the PolyPhen-2-based 90% CI MSC protein-coding human genes.

  7. 7.

    Supplementary Table 7

    A summary of the SIFT-based 99% CI MSC protein-coding human genes.

  8. 8.

    Supplementary Table 8

    A summary of the SIFT-based 95% CI MSC protein-coding human genes.

  9. 9.

    Supplementary Table 9

    A summary of the SIFT-based 90% CI MSC protein-coding human genes.

  10. 10.

    Supplementary Table 10

    KEGG pathway categories displaying high levels of enrichment among genes with low and high MSC scores.

  11. 11.

    Supplementary Table 11

    True positive and true negative prediction rates, HGMD-based.

  12. 12.

    Supplementary Table 12

    True positive and true negative prediction rates, ClinVar-based.

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DOI

https://doi.org/10.1038/nmeth.3739