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Quantifying and Improving Clinical-grade Coverage and Accuracy using Augmented Exome Sequencing



Justin M. Zook, Anil Patwardhan, Marc L. Salit, Carlos Bustamante, Euan Ashley, Michael Snyder, John West, Richard Chen


Exome sequencing is increasingly used for the clinical evaluation of genetic disease, yet accuracy and coverage in medically interpretable parts of the genome remains under-characterized. We evaluate recently developed exome sequencing platforms in the “medical exome”, a list of genomic regions causally implicated in disease and drug-response. In addition to the average depth and breadth of coverage of the constitutive exons, we compare error rates among standard exome and whole genome sequencing platforms. Coverage shortfalls are illustrated in well-characterized medically relevant genes, including several gaps encompassing known disease-associated variants. These gaps in clinical-grade coverage are due to a variety of sequence features and are recoverable using an augmented exome strategy that specifically targets biomedically and clinical important areas of the genome. The recovery of these gaps among medically relevant regions of the genome improves the sensitivity of exome-based sequencing tests, yielding a level of accuracy in the medical exome that is on parity with whole genome sequencing methods.
American Journal of Human Genetics


Zook, J. , Patwardhan, A. , Salit, M. , Bustamante, C. , Ashley, E. , Snyder, M. , West, J. and Chen, R. (2015), Quantifying and Improving Clinical-grade Coverage and Accuracy using Augmented Exome Sequencing, American Journal of Human Genetics, [online], (Accessed April 19, 2024)
Created July 16, 2015, Updated January 27, 2020