GeneBreaker - Variant simulation to improve the diagnosis of Mendelian rare genetic diseases
Phillip A. Richmond, T. V. Av-Shalom, O. Fornes
May 30, 2020
Citations
1
Citations
Journal
bioRxiv
Full text
Semantic Scholar
Key Takeaway Key Takeaway: GeneBreaker is a free tool that creates synthetic rare disease cases for testing variant calling approaches, evaluating variant prioritization, and training diagnostic practitioners in genomic medicine.
Abstract
Mendelian rare genetic diseases affect 5-10% of the population, and with over 5,300 genes responsible for ~7,000 different diseases, they are challenging to diagnose. The use of whole genome sequencing (WGS) has bolstered the diagnosis rate significantly. Effective use of WGS relies upon the ability to identify the disrupted gene responsible for disease phenotypes. This process involves genomic variant calling and prioritization, and is the beneficiary of improvements to sequencing technology, variant calling approaches, and increased capacity to prioritize genomic variants with potential pathogenicity. As analysis pipelines continue to improve, careful testing of their efficacy is paramount. However, real-life cases typically emerge anecdotally, and utilization of clinically sensitive and identifiable data for testing pipeline improvements is regulated and limiting. We identified the need for a gene-based variant simulation framework which can create mock rare disease scenarios, utilizing known pathogenic variants or through the creation of novel gene-disrupting variants. To fill this need, we present GeneBreaker, a tool which creates synthetic rare disease cases with utility for benchmarking variant calling approaches, testing the efficacy of variant prioritization, and as an educational mechanism for training diagnostic practitioners in the expanding field of genomic medicine. GeneBreaker is freely available at http://GeneBreaker.cmmt.ubc.ca.