Next-generation sequencing is coming to clinical diagnostics, but which one is more suitable for clinicians, whole exome or targeted sequencing? The problem with exome sequencing is incomplete coverage in some areas. The uncovered areas prevent analysis pipelines to find the genetic variants in those regions, a fact unknown to most users. The VCF 4.1 standard, the file format most variant callers produce, does not contain information about non-calls. The interpretation becomes unreliable if the uncovered regions are not reported. Even with exome sequencing, 97% of the genome is not covered. Therefore, it is essential to report the uncovered critical regions, e.g., known biomarkers. Our NGS analysis tool omnomicsNGS allows the user to define biomarkers consisting of one or more variants. Our software automatically calculates the results based on called variants and the read depth. Specifically, omnomicsNGS reports the absence or shortage of good quality reads covering the variant. As interpretation becomes more accurate, diagnostic protocols can be improved and, eventually, more lives can be saved.

The problems with exome sequencing can be avoided using targeted next-generation sequencing, which can be reliably implemented as a stand-alone diagnostic test [1]. On the other hand, exome sequencing gives superior results over targeted sequencing[2]. It seems that there is no clear answer which is better. The clinical laboratories should therefore invest in an insfrastructure supporting both whole exome and targeted sequencing, such as our omnomicsNGS.

[1] Sikkema-Raddatz, B., Johansson, L. F., de Boer, E. N., Almomani, R., Boven, L. G., van den Berg, M. P., van Spaendonck-Zwarts, K. Y., van Tintelen, J. P., Sijmons, R. H., Jongbloed, J. D. H. and Sinke, R. J. (2013), Targeted Next-Generation Sequencing can Replace Sanger Sequencing in Clinical Diagnostics. Hum. Mutat., 34: 1035–1042. doi: 10.1002/humu.22332[2] Howard J. Jacob, Ph.D., Next-Generation Sequencing for Clinical DiagnosticsN Engl J Med 2013; 369:1557-1558 October 17, 2013 DOI: 10.1056/NEJMe1310846

Submitted by Jussi Volanen

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