Journal article
A clinically driven variant prioritization framework outperforms purely computational approaches for the diagnostic analysis of singleton WES data
Z Stark, H Dashnow, S Lunke, TY Tan, A Yeung, S Sadedin, N Thorne, I MacCiocca, C Gaff, A Oshlack, SM White, PA James
European Journal of Human Genetics | NATURE PUBLISHING GROUP | Published : 2017
Abstract
Rapid identification of clinically significant variants is key to the successful application of next generation sequencing technologies in clinical practice. The Melbourne Genomics Health Alliance (MGHA) variant prioritization framework employs a gene prioritization index based on clinician-generated a priori gene lists, and a variant prioritization index (VPI) based on rarity, conservation and protein effect. We used data from 80 patients who underwent singleton whole exome sequencing (WES) to test the ability of the framework to rank causative variants highly, and compared it against the performance of other gene and variant prioritization tools. Causative variants were identified in 59 of..
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Funding Acknowledgements
We would like to acknowledge the Melbourne Genomics Health Alliance Steering Group, Genomics and Bioinformatics Advisory Group and the Clinical Interpretation Reporting Group for establishing the systems and standards applied in this study. The study was funded by the founding organizations of the Melbourne Genomics Health Alliance (Royal Melbourne Hospital, Royal Children's Hospital, University of Melbourne, Walter and Eliza Hall Institute, Murdoch Childrens Research Institute, Australian Genome Research Facility and CSIRO) and the State Government of Victoria (Department of Health and Human Services). The involvement of AGRF was supported by sponsorship from Bioplatforms Australia and the NCRIS program.