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dc.contributor.authorThouvenot, P
dc.contributor.authorBen Yamin, B
dc.contributor.authorFourriere, L
dc.contributor.authorLescure, A
dc.contributor.authorBoudier, T
dc.contributor.authorDel Nery, E
dc.contributor.authorChauchereau, A
dc.contributor.authorGoldgar, DE
dc.contributor.authorHoudayer, C
dc.contributor.authorStoppa-Lyonnet, D
dc.contributor.authorNicolas, A
dc.contributor.authorMillot, GA
dc.date.accessioned2020-12-09T23:21:06Z
dc.date.available2020-12-09T23:21:06Z
dc.date.issued2016-06-01
dc.identifierpii: PGENETICS-D-16-00586
dc.identifier.citationThouvenot, 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.
dc.identifier.issn1553-7404
dc.identifier.urihttp://hdl.handle.net/11343/253198
dc.description.abstractUnderstanding 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.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleFunctional Assessment of Genetic Variants with Outcomes Adapted to Clinical Decision-Making
dc.typeJournal Article
dc.identifier.doi10.1371/journal.pgen.1006096
melbourne.affiliation.departmentBiochemistry and Molecular Biology
melbourne.source.titlePLoS Genetics
melbourne.source.volume12
melbourne.source.issue6
dc.rights.licenseCC BY
melbourne.elementsid1306515
melbourne.contributor.authorFourriere-Chea, Lou
dc.identifier.eissn1553-7404
melbourne.accessrightsOpen Access


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