November 17, 2020, Vol 324, No. 19, Pages 1925-2006
Bioinformatics, Sequencing Accuracy, and the Credibility of Clinical Genomics
W. Gregory Feero, MD, PhD
JAMA. 2020;324(19):1945-1947. doi:10.1001/jama.2020.19939
The adoption of clinical exome and whole-genome sequencing based on next-generation sequencing technologies has increased rapidly over the last decade; this has been accelerated by increasing coverage of these services by private and public insurers.1,2 Examples of use include tumor and germline sequencing in patients with cancer, rapid turn-around sequencing of the genomes of critically ill neonates to diagnose mendelian conditions, and noninvasive prenatal testing for reproductive decision-making. The accuracy of sequencing results is of paramount importance to patients, clinicians, and those paying for testing services; inaccuracy can affect not only the tested individual, but their extended biological family.3 Understanding what accuracy means in the context of genome sequencing is a challenge. In the genomics community accuracy is often described using 2 terms: analytic validity, eg, does the sequencing process reliably detect variations that are present in an individual’s genome; and clinical validity, eg, are the variants detected reliably related to health outcomes.