Biochemistry of Chronic Diseases Laboratory, National Institute of Genomic Medicine, INMEGEN, Mexico City, Mexico.
Computational Genomics Department, National Institute of Genomic Medicine, INMEGEN, Mexico City, Mexico.
Sci Rep. 2022 Mar 19;12(1):4759. doi: 10.1038/s41598-022-07756-6.
End-point RT-PCR is a suitable alternative diagnostic technique since it is cheaper than RT-qPCR tests and can be implemented on a massive scale in low- and middle-income countries. In this work, a bioinformatic approach to guide the design of PCR primers was developed, and an alternative diagnostic test based on end-point PCR was designed. End-point PCR primers were designed through conservation analysis based on kmer frequency in SARS-CoV-2 and human respiratory pathogen genomes. Highly conserved regions were identified for primer design, and the resulting PCR primers were used to amplify 871 nasopharyngeal human samples with a previous RT-qPCR based SARS-CoV-2 diagnosis. The diagnostic test showed high accuracy in identifying SARS-CoV-2-positive samples including B.1.1.7, P.1, B.1.427/B.1.429 and B.1.617.2/ AY samples with a detection limit of 7.2 viral copies/µL. In addition, this test could discern SARS-CoV-2 infection from other viral infections with COVID-19-like symptomatology. The designed end-point PCR diagnostic test to detect SARS-CoV-2 is a suitable alternative to RT-qPCR. Since the proposed bioinformatic approach can be easily applied in thousands of viral genomes and over highly divergent strains, it can be used as a PCR design tool as new SARS-CoV-2 variants emerge. Therefore, this end-point PCR test could be employed in epidemiological surveillance to detect new SARS-CoV-2 variants as they emerge and propagate.
终点 RT-PCR 是一种合适的替代诊断技术,因为它比 RT-qPCR 测试便宜,并且可以在中低收入国家大规模实施。在这项工作中,开发了一种基于生物信息学的方法来指导 PCR 引物的设计,并设计了一种基于终点 PCR 的替代诊断测试。通过 SARS-CoV-2 和人类呼吸道病原体基因组中 kmer 频率的保守性分析,设计了终点 PCR 引物。确定了用于引物设计的高度保守区域,并用产生的 PCR 引物扩增了 871 份鼻咽人类样本,这些样本先前基于 RT-qPCR 进行了 SARS-CoV-2 诊断。该诊断测试在识别 SARS-CoV-2 阳性样本方面具有很高的准确性,包括 B.1.1.7、P.1、B.1.427/B.1.429 和 B.1.617.2/AY 样本,检测限为 7.2 个病毒拷贝/µL。此外,该测试可以区分 SARS-CoV-2 感染与具有 COVID-19 样症状的其他病毒感染。用于检测 SARS-CoV-2 的设计终点 PCR 诊断测试是 RT-qPCR 的合适替代方法。由于所提出的生物信息学方法可以轻松应用于数千种病毒基因组和高度变异的菌株,因此可以作为新的 SARS-CoV-2 变体出现时的 PCR 设计工具。因此,这种终点 PCR 测试可以用于流行病学监测,以检测新出现和传播的 SARS-CoV-2 变体。