Nature Communications (May 2024)

Crykey: Rapid identification of SARS-CoV-2 cryptic mutations in wastewater

  • Yunxi Liu,
  • Nicolae Sapoval,
  • Pilar Gallego-García,
  • Laura Tomás,
  • David Posada,
  • Todd J. Treangen,
  • Lauren B. Stadler

DOI
https://doi.org/10.1038/s41467-024-48334-w
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 13

Abstract

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Abstract 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.