PerspectiveGenetic Diseases

Deep Sequencing of Patient Genomes for Disease Diagnosis: When Will It Become Routine?

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Science Translational Medicine  15 Jun 2011:
Vol. 3, Issue 87, pp. 87ps23
DOI: 10.1126/scitranslmed.3002695


  • Fig. 1. Contrasting technologies.

    Frequency of sequences is plotted versus depth of sequence coverage to show, for comparison purposes, the patterns of distribution of sequence coverage afforded by research-grade WGS (blue line) and exome-seq/targeted NGS (red line). The genome coverage achieved by WGS is symmetric about the mean, which at this time is typically 30-fold coverage. Approximately 5% of the genome has insufficient coverage to allow variants to be detected (dotted white line). In contrast, the genome coverage achieved by exome-seq and targeted NGS is right-skewed. Thus, approximately 100-fold average coverage is necessary to achieve a sensitivity of variant detection similar to WGS.

  • Fig. 2.

    Fast forward? Shown are the major similarities and differences in refinements needed for diagnostic use (DX) of WGS, exome-seq, and targeted NGS. The average depth of coverage differs in each approach. Reflex confirmatory testing of all clinically relevant results is necessary for WGS and exome-seq but probably not for targeted NGS; this is because it is possible to obtain a large number of independent observations of each sequence variant. All three methods require pathological interpretation and reporting by a certified laboratory director.


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