Estimating the relative proportions of SARS-CoV-2 haplotypes from wastewater samples

Research output: Contribution to journalJournal articleResearchpeer-review

Documents

  • Fulltext

    Final published version, 2.54 MB, PDF document

Wastewater surveillance has become essential for monitoring the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The quantification of SARS-CoV-2 RNA in wastewater correlates with the coronavirus disease 2019 (COVID-19) caseload in a community. However, estimating the proportions of different SARS-CoV-2 haplotypes has remained technically difficult. We present a phylogenetic imputation method for improving the SARS-CoV-2 reference database and a method for estimating the relative proportions of SARS-CoV-2 haplotypes from wastewater samples. The phylogenetic imputation method uses the global SARS-CoV-2 phylogeny and imputes based on the maximum of the posterior probability of each nucleotide. We show that the imputation method has error rates comparable to, or lower than, typical sequencing error rates, which substantially improves the reference database and allows for accurate inferences of haplotype composition. Our method for estimating relative proportions of haplotypes uses an initial step to remove unlikely haplotypes and an expectation maximization (EM) algorithm for obtaining maximum likelihood estimates of the proportions of different haplotypes in a sample. Using simulations with a reference database of >3 million SARS-CoV-2 genomes, we show that the estimated proportions reflect the true proportions given sufficiently high sequencing depth.

Original languageEnglish
Article number100313
JournalCell Reports Methods
Volume2
Issue number10
DOIs
Publication statusPublished - 2022

Bibliographical note

Publisher Copyright:
© 2022 The Author(s)

    Research areas

  • COVID-19, expectation maximization, imputation, SARS-CoV-2, wastewater surveillance, wastewater-based epidemiology

ID: 331788323