937 lines
79 KiB
Text
937 lines
79 KiB
Text
<!DOCTYPE html>
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<h1 class="nist-page__title">Clinical Implications of Technical Performance in Medical Genome Sequencing</h1>
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<div class="nist-field__item"><time datetime="2016-03-02T12:00:00Z">March 2, 2016</time>
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<h3 class="nist-field__label">Author(s)</h3>
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<div class="nist-field__item"><span class="nist-author">Justin M. Zook</span>, James Priest, Rachel Goldfeder, Megan Grove, Daryl Waggott, Matthew Wheeler, Euan Ashley, <span class="nist-author">Marc L. Salit</span></div>
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<h3>Abstract</h3>
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As next-generation sequencing is becoming routinely applied to clinical care, the predictive characteristics and limitations of whole exome and whole genome sequencing need to be well-understood. The Genome in a Bottle Consortium has recently published a set of benchmark SNP, indel, and homozygous reference genotypes for the pilot candidate whole genome NIST Reference Material based on NA12878. We use these benchmark calls to assess the sensitivity and positive predictive value for two representative sequencing pipelines from this single individual. We observe that the accuracy of a variant call depends on the genomic region, variant type, and read depth, and varies by analytical pipeline. We also identify sites that are prone to sequencing errors for this genome, including thousands that are present in publicly available variant databases. We examine the clinical impact of mandatory reporting of secondary findings, highlighting a false positive variant found in BRCA2. Together, these data illustrate the necessity of applying and reporting technical benchmarks to ensure accurate and judicious interpretation of next-generation DNA sequencing results in the clinic.
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<div class="nist-field__item">American Journal of Human Genetics</div>
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Zook, J.
|
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, Priest, J.
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, Goldfeder, R.
|
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, Grove, M.
|
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, Waggott, D.
|
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, Wheeler, M.
|
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, Ashley, E.
|
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and Salit, M.
|
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(2016),
|
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Clinical Implications of Technical Performance in Medical Genome Sequencing, American Journal of Human Genetics, [online], https://doi.org/10.1186/s13073-016-0269-0
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(Accessed March 4, 2025)
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Created March 2, 2016, Updated January 27, 2020
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