Using intrahost single nucleotide variant data to predict SARS-CoV-2 detection cycle threshold values.


Journal

PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081

Informations de publication

Date de publication:
2024
Historique:
received: 23 04 2024
accepted: 10 10 2024
medline: 31 10 2024
pubmed: 30 10 2024
entrez: 30 10 2024
Statut: epublish

Résumé

Over the last four years, each successive wave of the COVID-19 pandemic has been caused by variants with mutations that improve the transmissibility of the virus. Despite this, we still lack tools for predicting clinically important features of the virus. In this study, we show that it is possible to predict the PCR cycle threshold (Ct) values from clinical detection assays using sequence data. Ct values often correspond with patient viral load and the epidemiological trajectory of the pandemic. Using a collection of 36,335 high quality genomes, we built models from SARS-CoV-2 intrahost single nucleotide variant (iSNV) data, computing XGBoost models from the frequencies of A, T, G, C, insertions, and deletions at each position relative to the Wuhan-Hu-1 reference genome. Our best model had an R2 of 0.604 [0.593-0.616, 95% confidence interval] and a Root Mean Square Error (RMSE) of 5.247 [5.156-5.337], demonstrating modest predictive power. Overall, we show that the results are stable relative to an external holdout set of genomes selected from SRA and are robust to patient status and the detection instruments that were used. This study highlights the importance of developing modeling strategies that can be applied to publicly available genome sequence data for use in disease prevention and control.

Identifiants

pubmed: 39475880
doi: 10.1371/journal.pone.0312686
pii: PONE-D-24-10210
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e0312686

Informations de copyright

Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Déclaration de conflit d'intérêts

The authors have declared that no competing interests exist.

Auteurs

Lea Duesterwald (L)

College of Engineering, Cornell University, Ithaca, NY, United States of America.
Northwestern-Argonne Institute for Science and Engineering, Evanston, IL, United States of America.

Marcus Nguyen (M)

Northwestern-Argonne Institute for Science and Engineering, Evanston, IL, United States of America.
Data Science and Learning Division, Argonne National Laboratory, Lemont, IL, United States of America.
Consortium for Advanced Science and Engineering, University of Chicago, Chicago, IL, United States of America.

Paul Christensen (P)

Laboratory of Human Molecular and Translational Human Infectious Diseases, Center for Infectious Diseases, Houston Methodist Research Institute and Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, United States of America.
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York City, NY, United States of America.

S Wesley Long (SW)

Laboratory of Human Molecular and Translational Human Infectious Diseases, Center for Infectious Diseases, Houston Methodist Research Institute and Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, United States of America.
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York City, NY, United States of America.

Randall J Olsen (RJ)

Laboratory of Human Molecular and Translational Human Infectious Diseases, Center for Infectious Diseases, Houston Methodist Research Institute and Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, United States of America.
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York City, NY, United States of America.

James M Musser (JM)

Laboratory of Human Molecular and Translational Human Infectious Diseases, Center for Infectious Diseases, Houston Methodist Research Institute and Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, United States of America.
Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York City, NY, United States of America.

James J Davis (JJ)

Northwestern-Argonne Institute for Science and Engineering, Evanston, IL, United States of America.
Data Science and Learning Division, Argonne National Laboratory, Lemont, IL, United States of America.
Consortium for Advanced Science and Engineering, University of Chicago, Chicago, IL, United States of America.

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