eXtasy: variant prioritization by genomic data fusion

Journal name:
Nature Methods
Volume:
10,
Pages:
1083–1084
Year published:
DOI:
doi:10.1038/nmeth.2656
Received
Accepted
Published online

Massively parallel sequencing greatly facilitates the discovery of novel disease genes causing Mendelian and oligogenic disorders. However, many mutations are present in any individual genome, and identifying which ones are disease causing remains a largely open problem. We introduce eXtasy, an approach to prioritize nonsynonymous single-nucleotide variants (nSNVs) that substantially improves prediction of disease-causing variants in exome sequencing data by integrating variant impact prediction, haploinsufficiency prediction and phenotype-specific gene prioritization.

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Author information

  1. These authors contributed equally to this work.

    • Alejandro Sifrim &
    • Dusan Popovic

Affiliations

  1. Department of Electrical Engineering, STADIUS Center for Dynamical Systems, Signal Processing and Data Analytics, KU Leuven, Leuven, Belgium.

    • Alejandro Sifrim,
    • Dusan Popovic,
    • Leon-Charles Tranchevent,
    • Amin Ardeshirdavani,
    • Ryo Sakai,
    • Peter Konings,
    • Jan Aerts,
    • Bart De Moor &
    • Yves Moreau
  2. iMinds Future Health Department, Leuven, Belgium.

    • Alejandro Sifrim,
    • Dusan Popovic,
    • Leon-Charles Tranchevent,
    • Amin Ardeshirdavani,
    • Ryo Sakai,
    • Peter Konings,
    • Jan Aerts,
    • Bart De Moor &
    • Yves Moreau
  3. Laboratory of Molecular Cytogenetics and Genome Research, KU Leuven, Leuven, Belgium.

    • Joris R Vermeesch

Contributions

A.S., D.P. and Y.M. conceptually defined the project. A.S. and D.P. wrote the initial draft of the manuscript and performed the analyses. A.S. generated the data sets and developed the software tools. D.P. developed the benchmarks and trained the models. L.-C.T. and A.S. computed the Endeavour gene prioritizations. A.A. and A.S. developed the web tool. R.S. and J.A. advised on data visualization and visual analytics. P.K. advised on statistical concerns. J.R.V. advised on genetical concerns. All authors revised and proofread the paper. B.D.M. cosupervised the project. Y.M. supervised the project.

Competing financial interests

The authors declare no competing financial interests.

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