Department of Computer Science, Rice University, Houston, TX, 77005, USA.
CINBIO, Universidade de Vigo, 36310, Vigo, Spain.
Nat Commun. 2024 May 28;15(1):4545. doi: 10.1038/s41467-024-48334-w.
Wastewater surveillance for SARS-CoV-2 provides early warnings of emerging variants of concerns and can be used to screen for novel cryptic linked-read mutations, which are co-occurring single nucleotide mutations that are rare, or entirely missing, in existing SARS-CoV-2 databases. While previous approaches have focused on specific regions of the SARS-CoV-2 genome, there is a need for computational tools capable of efficiently tracking cryptic mutations across the entire genome and investigating their potential origin. We present Crykey, a tool for rapidly identifying rare linked-read mutations across the genome of SARS-CoV-2. We evaluated the utility of Crykey on over 3,000 wastewater and over 22,000 clinical samples; our findings are three-fold: i) we identify hundreds of cryptic mutations that cover the entire SARS-CoV-2 genome, ii) we track the presence of these cryptic mutations across multiple wastewater treatment plants and over three years of sampling in Houston, and iii) we find a handful of cryptic mutations in wastewater mirror cryptic mutations in clinical samples and investigate their potential to represent real cryptic lineages. In summary, Crykey enables large-scale detection of cryptic mutations in wastewater that represent potential circulating cryptic lineages, serving as a new computational tool for wastewater surveillance of SARS-CoV-2.
污水监测 SARS-CoV-2 可提前预警关注的变异株出现，并可用于筛查新型隐匿连锁阅读突变，这些突变是在现有 SARS-CoV-2 数据库中罕见或完全缺失的共发生单核苷酸突变。虽然以前的方法集中在 SARS-CoV-2 基因组的特定区域，但需要能够有效地在整个基因组中跟踪隐匿突变并研究其潜在起源的计算工具。我们提出了 Crykey，这是一种用于快速识别 SARS-CoV-2 基因组中罕见连锁阅读突变的工具。我们在 3000 多个污水样本和 22000 多个临床样本上评估了 Crykey 的效用；我们的发现有三个方面：i）我们识别出了数百个覆盖 SARS-CoV-2 整个基因组的隐匿突变，ii）我们追踪了这些隐匿突变在休斯顿多个污水处理厂和三年多的采样中的存在情况，iii）我们在污水中发现了少数几个与临床样本中的隐匿突变相匹配的隐匿突变，并研究了它们是否代表真正的隐匿谱系。总之，Crykey 能够大规模检测污水中的隐匿突变，这些突变代表潜在的循环隐匿谱系，是 SARS-CoV-2 污水监测的一种新的计算工具。
