A verified genomic reference sample for assessing performance of cancer panels detecting small variants of low allele frequency

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F21%3A00120109" target="_blank" >RIV/00216224:14740/21:00120109 - isvavai.cz</a>

Result on the web

<a href="https://genomebiology.biomedcentral.com/track/pdf/10.1186/s13059-021-02316-z.pdf" target="_blank" >https://genomebiology.biomedcentral.com/track/pdf/10.1186/s13059-021-02316-z.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s13059-021-02316-z" target="_blank" >10.1186/s13059-021-02316-z</a>

Result language

angličtina

Original language name

A verified genomic reference sample for assessing performance of cancer panels detecting small variants of low allele frequency

Original language description

BackgroundOncopanel genomic testing, which identifies important somatic variants, is increasingly common in medical practice and especially in clinical trials. Currently, there is a paucity of reliable genomic reference samples having a suitably large number of pre-identified variants for properly assessing oncopanel assay analytical quality and performance. The FDA-led Sequencing and Quality Control Phase 2 (SEQC2) consortium analyze ten diverse cancer cell lines individually and their pool, termed Sample A, to develop a reference sample with suitably large numbers of coding positions with known (variant) positives and negatives for properly evaluating oncopanel analytical performance.ResultsIn reference Sample A, we identify more than 40,000 variants down to 1% allele frequency with more than 25,000 variants having less than 20% allele frequency with 1653 variants in COSMIC-related genes. This is 5-100x more than existing commercially available samples. We also identify an unprecedented number of negative positions in coding regions, allowing statistical rigor in assessing limit-of-detection, sensitivity, and precision. Over 300 loci are randomly selected and independently verified via droplet digital PCR with 100% concordance. Agilent normal reference Sample B can be admixed with Sample A to create new samples with a similar number of known variants at much lower allele frequency than what exists in Sample A natively, including known variants having allele frequency of 0.02%, a range suitable for assessing liquid biopsy panels.ConclusionThese new reference samples and their admixtures provide superior capability for performing oncopanel quality control, analytical accuracy, and validation for small to large oncopanels and liquid biopsy assays.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30101 - Human genetics

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2021

Confidentiality

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

Name of the periodical

GENOME BIOLOGY

ISSN

1474-760X

e-ISSN

—

Volume of the periodical

22

Issue of the periodical within the volume

1

Country of publishing house

GB - UNITED KINGDOM

Number of pages

38

Pages from-to

111

UT code for WoS article

000641654300003

EID of the result in the Scopus database

2-s2.0-85104284947