Brief Communication

Phen-Gen: combining phenotype and genotype to analyze rare disorders

  • Nature Methods volume 11, pages 935937 (2014)
  • doi:10.1038/nmeth.3046
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Abstract

We introduce Phen-Gen, a method that combines patients' disease symptoms and sequencing data with prior domain knowledge to identify the causative genes for rare disorders. Simulations revealed that the causal variant was ranked first in 88% of cases when it was a coding variant—a 52% advantage over a genotype-only approach—and Phen-Gen outperformed other existing prediction methods by 13–58%. If disease etiology was unknown, the causal variant was assigned the top rank in 71% of simulations. Phen-Gen is available at http://phen-gen.org/.

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Acknowledgements

This work was supported by the Agency for Science, Technology and Research (A*STAR), Singapore. We thank Radboud University Nijmegen Medical Centre for sharing the 100 intellectual disability patient data sets, particularly J. de Ligt for his help with this data. We also thank S. Köhler for his help with Phenomizer, N. Jinawath for her help interpreting patient symptoms, and S. Prabhakar and N. Clarke for their comments on the genomic predictor. We thank S. Prabhakar, S. Davila, A. Wilm and R. del Rosario for their comments on the manuscript.

Author information

Affiliations

  1. Computational and Systems Biology Group, Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore.

    • Asif Javed
    • , Saloni Agrawal
    •  & Pauline C Ng

Authors

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Contributions

A.J. conceived of and designed the project, designed and implemented the analysis framework, implemented methods, conducted experiments, interpreted results, wrote the initial manuscript and revised and proofread the paper. S.A. implemented methods, conducted experiments, set up the web server and revised and proofread the paper. P.C.N. conceived of and designed the project, revised and proofread the paper and supervised the project.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Asif Javed or Pauline C Ng.

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    Supplementary Figures 1–9, Supplementary Tables 1–7 and Supplementary Note