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Bayesian Binary Mixture Models as a Flexible Alternative to Cut-Off Analysis of ELISA Results, a Case Study of Seoul Orthohantavirus

Serological assays, such as the enzyme-linked immunosorbent assay (ELISA), are popular tools for establishing the seroprevalence of various infectious diseases in humans and animals. In the ELISA, the optical density is measured and gives an indication of the antibody level. However, there is variab...

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Autores principales: Swart, Arno, Maas, Miriam, de Vries, Ankje, Cuperus, Tryntsje, Opsteegh, Marieke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234822/
https://www.ncbi.nlm.nih.gov/pubmed/34208752
http://dx.doi.org/10.3390/v13061155
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author Swart, Arno
Maas, Miriam
de Vries, Ankje
Cuperus, Tryntsje
Opsteegh, Marieke
author_facet Swart, Arno
Maas, Miriam
de Vries, Ankje
Cuperus, Tryntsje
Opsteegh, Marieke
author_sort Swart, Arno
collection PubMed
description Serological assays, such as the enzyme-linked immunosorbent assay (ELISA), are popular tools for establishing the seroprevalence of various infectious diseases in humans and animals. In the ELISA, the optical density is measured and gives an indication of the antibody level. However, there is variability in optical density values for individuals that have been exposed to the pathogen of interest, as well as individuals that have not been exposed. In general, the distribution of values that can be expected for these two categories partly overlap. Often, a cut-off value is determined to decide which individuals should be considered seropositive or seronegative. However, the classical cut-off approach based on a putative threshold ignores heterogeneity in immune response in the population and is thus not the optimal solution for the analysis of serological data. A binary mixture model does include this heterogeneity, offers measures of uncertainty and the direct estimation of seroprevalence without the need for correction based on sensitivity and specificity. Furthermore, the probability of being seropositive can be estimated for individual samples, and both continuous and categorical covariates (risk-factors) can be included in the analysis. Using ELISA results from rats tested for the Seoul orthohantavirus, we compared the classical cut-off method with a binary mixture model set in a Bayesian framework. We show that it performs similarly or better than cut-off methods, by comparing with real-time quantitative polymerase chain reaction (RT-qPCR) results. We therefore recommend binary mixture models as an analysis tool over classical cut-off methods. An example code is included to facilitate the practical use of binary mixture models in everyday practice.
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spelling pubmed-82348222021-06-27 Bayesian Binary Mixture Models as a Flexible Alternative to Cut-Off Analysis of ELISA Results, a Case Study of Seoul Orthohantavirus Swart, Arno Maas, Miriam de Vries, Ankje Cuperus, Tryntsje Opsteegh, Marieke Viruses Article Serological assays, such as the enzyme-linked immunosorbent assay (ELISA), are popular tools for establishing the seroprevalence of various infectious diseases in humans and animals. In the ELISA, the optical density is measured and gives an indication of the antibody level. However, there is variability in optical density values for individuals that have been exposed to the pathogen of interest, as well as individuals that have not been exposed. In general, the distribution of values that can be expected for these two categories partly overlap. Often, a cut-off value is determined to decide which individuals should be considered seropositive or seronegative. However, the classical cut-off approach based on a putative threshold ignores heterogeneity in immune response in the population and is thus not the optimal solution for the analysis of serological data. A binary mixture model does include this heterogeneity, offers measures of uncertainty and the direct estimation of seroprevalence without the need for correction based on sensitivity and specificity. Furthermore, the probability of being seropositive can be estimated for individual samples, and both continuous and categorical covariates (risk-factors) can be included in the analysis. Using ELISA results from rats tested for the Seoul orthohantavirus, we compared the classical cut-off method with a binary mixture model set in a Bayesian framework. We show that it performs similarly or better than cut-off methods, by comparing with real-time quantitative polymerase chain reaction (RT-qPCR) results. We therefore recommend binary mixture models as an analysis tool over classical cut-off methods. An example code is included to facilitate the practical use of binary mixture models in everyday practice. MDPI 2021-06-16 /pmc/articles/PMC8234822/ /pubmed/34208752 http://dx.doi.org/10.3390/v13061155 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Swart, Arno
Maas, Miriam
de Vries, Ankje
Cuperus, Tryntsje
Opsteegh, Marieke
Bayesian Binary Mixture Models as a Flexible Alternative to Cut-Off Analysis of ELISA Results, a Case Study of Seoul Orthohantavirus
title Bayesian Binary Mixture Models as a Flexible Alternative to Cut-Off Analysis of ELISA Results, a Case Study of Seoul Orthohantavirus
title_full Bayesian Binary Mixture Models as a Flexible Alternative to Cut-Off Analysis of ELISA Results, a Case Study of Seoul Orthohantavirus
title_fullStr Bayesian Binary Mixture Models as a Flexible Alternative to Cut-Off Analysis of ELISA Results, a Case Study of Seoul Orthohantavirus
title_full_unstemmed Bayesian Binary Mixture Models as a Flexible Alternative to Cut-Off Analysis of ELISA Results, a Case Study of Seoul Orthohantavirus
title_short Bayesian Binary Mixture Models as a Flexible Alternative to Cut-Off Analysis of ELISA Results, a Case Study of Seoul Orthohantavirus
title_sort bayesian binary mixture models as a flexible alternative to cut-off analysis of elisa results, a case study of seoul orthohantavirus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8234822/
https://www.ncbi.nlm.nih.gov/pubmed/34208752
http://dx.doi.org/10.3390/v13061155
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