Evaluating the analytical validity of circulating tumor DNA sequencing assays for precision oncology

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Evaluating the analytical validity of circulating tumor DNA sequencing assays for precision oncology

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Evaluating the analytical validity of circulating tumor DNA sequencing assays for precision oncology

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10609 - Biochemical research methods

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nature biotechnology

ISSN

1087-0156

e-ISSN

—

Svazek periodika

39

Číslo periodika v rámci svazku

9

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

19

Strana od-do

1115-1128

Kód UT WoS článku

000639633800003

EID výsledku v databázi Scopus

2-s2.0-85104365330