University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Melbourne Medical School
  • Biochemistry and Molecular Biology
  • Biochemistry and Molecular Biology - Research Publications
  • View Item
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Melbourne Medical School
  • Biochemistry and Molecular Biology
  • Biochemistry and Molecular Biology - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

    Functional Assessment of Genetic Variants with Outcomes Adapted to Clinical Decision-Making

    Thumbnail
    Download
    Published version (2.539Mb)

    Citations
    Scopus
    Web of Science
    Altmetric
    13
    10
    Author
    Thouvenot, P; Ben Yamin, B; Fourriere, L; Lescure, A; Boudier, T; Del Nery, E; Chauchereau, A; Goldgar, DE; Houdayer, C; Stoppa-Lyonnet, D; ...
    Date
    2016-06-01
    Source Title
    PLoS Genetics
    Publisher
    PUBLIC LIBRARY SCIENCE
    University of Melbourne Author/s
    Fourriere-Chea, Lou
    Affiliation
    Biochemistry and Molecular Biology
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Thouvenot, P., Ben Yamin, B., Fourriere, L., Lescure, A., Boudier, T., Del Nery, E., Chauchereau, A., Goldgar, D. E., Houdayer, C., Stoppa-Lyonnet, D., Nicolas, A. & Millot, G. A. (2016). Functional Assessment of Genetic Variants with Outcomes Adapted to Clinical Decision-Making. PLOS GENETICS, 12 (6), https://doi.org/10.1371/journal.pgen.1006096.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/253198
    DOI
    10.1371/journal.pgen.1006096
    Abstract
    Understanding the medical effect of an ever-growing number of human variants detected is a long term challenge in genetic counseling. Functional assays, based on in vitro or in vivo evaluations of the variant effects, provide essential information, but they require robust statistical validation, as well as adapted outputs, to be implemented in the clinical decision-making process. Here, we assessed 25 pathogenic and 15 neutral missense variants of the BRCA1 breast/ovarian cancer susceptibility gene in four BRCA1 functional assays. Next, we developed a novel approach that refines the variant ranking in these functional assays. Lastly, we developed a computational system that provides a probabilistic classification of variants, adapted to clinical interpretation. Using this system, the best functional assay exhibits a variant classification accuracy estimated at 93%. Additional theoretical simulations highlight the benefit of this ready-to-use system in the classification of variants after functional assessment, which should facilitate the consideration of functional evidences in the decision-making process after genetic testing. Finally, we demonstrate the versatility of the system with the classification of siRNAs tested for human cell growth inhibition in high throughput screening.

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [53102]
    • Biochemistry and Molecular Biology - Research Publications [1075]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors