The development and validation of clinical exome-based panels using ExomeSlicer: Considerations and proof of concept using an Epilepsy panel

Publication date: Available online 22 June 2018Source: The Journal of Molecular DiagnosticsAuthor(s): Rojeen Niazi, Michael A. Gonzalez, Jorune Balciuniene, Perry Evans, Mahdi Sarmady, Ahmad N. Abou TayounAbstractExome-based panels are becoming the preferred diagnostic strategy in clinical laboratories. This approach enables dynamic gene content update and, if needed, cost-effective reflex to whole exome sequencing. There are currently no guidelines or appropriate resources to support the clinical implementation of exome-based panels. Here, we highlight principles and important considerations for the clinical development and validation of exome-based panels. In addition, we developed ExomeSlicer, a novel, web-based resource, which uses empirical exon-level next-generation sequencing quality metrics to predict and visualize technically challenging exome-wide regions in any gene(s) of interest. Exome sequencing data from 100 clinical epilepsy cases was used to illustrate the clinical utility of ExomeSlicer in predicting poor quality regions and its impact on streamlining the ad hoc Sanger sequencing fill in burden. Using ExomeSlicer,> 2,100 low complexity and/or high homology regions impacting>1,615 genes across the exome were also characterized. These regions can be a source of false positive or false negative variant calls, which can lead to misdiagnoses in tested patients and/or inaccurate functional annotations. We provide important considerations and a novel resource for t...
Source: The Journal of Molecular Diagnostics - Category: Pathology Source Type: research