The spike gene target failure (SGTF) genomic signature is highly accurate for the identification of Alpha and Omicron SARS-CoV-2 variants.

The spike gene target failure (SGTF) genomic signature is highly accurate for the identification of Alpha and Omicron SARS-CoV-2 variants.
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DOI:
10.1038/s41598-022-21564-y
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发表时间:
2022-11-08
期刊:
影响因子:
4.6
通讯作者:
Babady, N. Esther
Babady, N. Esther
中科院分区:
综合性期刊3区
文献类型:
--
作者:
McMillen, Tracy;Jani, Krupa;Robilotti, Elizabeth, V;Kamboj, Mini;Babady, N. Esther

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α (B.1.1.7)和Omicron (B.1.1.529, BA.1, BA.4和BA.5)变体(VOC)在其刺突基因上有几个共同的突变,包括导致刺突蛋白中69和70号位置(del 69 - 70)两个氨基酸缺失的突变。Del 69-70导致在广泛使用的商业测试TaqPath SARS-CoV-2 RT-PCR (Thermo Fisher)上检测不到S基因靶标。利用S基因靶失标(SGTF)特征初步推断出α和Omicron VOC的存在。我们通过分析2020年12月至2022年7月期间TaqPath RT-PCR检测的所有阳性SARS-CoV-2样本,并通过下一代测序对其进行测序,评估了SGTF特征识别这两个变体的准确性。成功测序2324份样本,其中SGTF阳性样本914份。Alpha变异SGTF特征的敏感性和特异性分别为99.6% (95% CI 96.1-99.9%)和98.6% (95% CI 99.2-99.8%), Omicron变异SGTF特征的敏感性和特异性分别为99.6% (95% CI 98.9-99.9%)和99.8% (95% CI 99.4-99.9%)。在相应波的峰值,SGTF对Alpha的阳性预测值为98%,对Omicron的阳性预测值为100%。SGTF标记的准确性很高,使这种基因组标记成为在现实世界的实验室环境中识别这些变异的快速和准确的代理。
The Alpha (B.1.1.7) and Omicron (B.1.1.529, BA.1, BA.4 and BA.5) variants of concern (VOC) share several mutations in their spike gene, including mutations resulting in the deletion of two amino acids at position 69 and 70 (del 69–70) in the Spike protein. Del 69–70 causes failure to detect the S gene target on a widely used, commercial test, the TaqPath SARS-CoV-2 RT-PCR (Thermo Fisher). The S gene target failure (SGTF) signature has been used to preliminarily infer the presence of Alpha and Omicron VOC. We evaluated the accuracy of the SGTF signature in identifying these two variants through analysis of all positive SARS-CoV-2 samples tested on the TaqPath RT-PCR and sequenced by next generation sequencing between December 2020 to July 2022. 2324 samples were successfully sequenced including 914 SGTF positive samples. The sensitivity and specificity of the SGTF signature was 99.6% (95% CI 96.1–99.9%) and 98.6% (95% CI 99.2–99.8%) for the Alpha variant and 99.6% (95% CI 98.9–99.9%) and 99.8% (95% CI 99.4–99.9%) for the Omicron variant. At the peak of their corresponding wave, the positive predictive value of the SGTF was 98% for Alpha and 100% for Omicron. The accuracy of the SGTF signature was high, making this genomic signature a rapid and accurate proxy for identification of these variants in real-world laboratory settings.
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