Evaluating the analytical validity of circulating tumor DNA sequencing assays for precision oncology
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F21%3A00123352" target="_blank" >RIV/00216224:14740/21:00123352 - isvavai.cz</a>
Result on the web
<a href="https://www.nature.com/articles/s41587-021-00857-z" target="_blank" >https://www.nature.com/articles/s41587-021-00857-z</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41587-021-00857-z" target="_blank" >10.1038/s41587-021-00857-z</a>
Alternative languages
Result language
angličtina
Original language name
Evaluating the analytical validity of circulating tumor DNA sequencing assays for precision oncology
Original language description
Reliable detection of mutations below 0.5% variant allele frequency remains a key challenge for circulating tumor DNA sequencing assays. Circulating tumor DNA (ctDNA) sequencing is being rapidly adopted in precision oncology, but the accuracy, sensitivity and reproducibility of ctDNA assays is poorly understood. Here we report the findings of a multi-site, cross-platform evaluation of the analytical performance of five industry-leading ctDNA assays. We evaluated each stage of the ctDNA sequencing workflow with simulations, synthetic DNA spike-in experiments and proficiency testing on standardized, cell-line-derived reference samples. Above 0.5% variant allele frequency, ctDNA mutations were detected with high sensitivity, precision and reproducibility by all five assays, whereas, below this limit, detection became unreliable and varied widely between assays, especially when input material was limited. Missed mutations (false negatives) were more common than erroneous candidates (false positives), indicating that the reliable sampling of rare ctDNA fragments is the key challenge for ctDNA assays. This comprehensive evaluation of the analytical performance of ctDNA assays serves to inform best practice guidelines and provides a resource for precision oncology.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10609 - Biochemical research methods
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2021
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature biotechnology
ISSN
1087-0156
e-ISSN
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Volume of the periodical
39
Issue of the periodical within the volume
9
Country of publishing house
DE - GERMANY
Number of pages
19
Pages from-to
1115-1128
UT code for WoS article
000639633800003
EID of the result in the Scopus database
2-s2.0-85104365330