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Improved Specificity and False Discovery Rates for Multiplex Analysis of Changes in Strain-Specific Anti-Influenza IgG

We describe a statistical approach to compare absolute antibody concentrations, both within and across subjects, derived from a multidimensional measurement of IgG binding to the influenza surface receptor hemagglutinin (HA). This approach addresses a fundamental problem in the field of vaccine immu...

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Autores principales: Li, Dongmei, Wang, Jiong, Treanor, John J., Zand, Martin S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501432/
https://www.ncbi.nlm.nih.gov/pubmed/31178920
http://dx.doi.org/10.1155/2019/3053869
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author Li, Dongmei
Wang, Jiong
Treanor, John J.
Zand, Martin S.
author_facet Li, Dongmei
Wang, Jiong
Treanor, John J.
Zand, Martin S.
author_sort Li, Dongmei
collection PubMed
description We describe a statistical approach to compare absolute antibody concentrations, both within and across subjects, derived from a multidimensional measurement of IgG binding to the influenza surface receptor hemagglutinin (HA). This approach addresses a fundamental problem in the field of vaccine immunology: how to accurately compare the levels of antibodies against multiple influenza strains. The mPlex-Flu assay can simultaneously measure the concentration of IgG antibodies against up to 50 influenza strains with only ≤10  μl of serum. It yields mean fluorescence intensity (MFI) over a 4-log range with low inter- and intrasample variability. While comparison of IgG binding to a single HA between subjects is straightforward, variations in binding behavior across influenza strains, coupled with reagent variations, make quantifying and comparing binding between multiple HA subtypes within subjects challenging. In this paper, we first treat such HA variations as an independent antigen and calculate each subtype antibody concentration using its own standard curve, normalizing variations in HA binding. We applied this method to the analyses of data from an H5 influenza clinical vaccine study. The results demonstrated that there are differences in coefficient estimates and in results of “comparing groups” between those with versus those without consideration of subtype antibody variations. Then, we used simulation studies to show the importance of taking the subtype antibody variations into account in HA strain antibody data analysis. Using a common standard curve for all subtype antibodies resulted in both inflated type I error and lowered specificity when comparing different treatment groups. Our results suggest that using individual standard curves for each influenza HA strain, and independently calculating anti-HA IgG concentrations, allows for adjustment of influenza HA subtype variations in treatment group comparisons in clinical vaccine studies. This method facilitates the direct comparison of serum anti-HA IgG concentrations against different influenza HA subtypes for multiplex assays.
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spelling pubmed-65014322019-06-09 Improved Specificity and False Discovery Rates for Multiplex Analysis of Changes in Strain-Specific Anti-Influenza IgG Li, Dongmei Wang, Jiong Treanor, John J. Zand, Martin S. Comput Math Methods Med Research Article We describe a statistical approach to compare absolute antibody concentrations, both within and across subjects, derived from a multidimensional measurement of IgG binding to the influenza surface receptor hemagglutinin (HA). This approach addresses a fundamental problem in the field of vaccine immunology: how to accurately compare the levels of antibodies against multiple influenza strains. The mPlex-Flu assay can simultaneously measure the concentration of IgG antibodies against up to 50 influenza strains with only ≤10  μl of serum. It yields mean fluorescence intensity (MFI) over a 4-log range with low inter- and intrasample variability. While comparison of IgG binding to a single HA between subjects is straightforward, variations in binding behavior across influenza strains, coupled with reagent variations, make quantifying and comparing binding between multiple HA subtypes within subjects challenging. In this paper, we first treat such HA variations as an independent antigen and calculate each subtype antibody concentration using its own standard curve, normalizing variations in HA binding. We applied this method to the analyses of data from an H5 influenza clinical vaccine study. The results demonstrated that there are differences in coefficient estimates and in results of “comparing groups” between those with versus those without consideration of subtype antibody variations. Then, we used simulation studies to show the importance of taking the subtype antibody variations into account in HA strain antibody data analysis. Using a common standard curve for all subtype antibodies resulted in both inflated type I error and lowered specificity when comparing different treatment groups. Our results suggest that using individual standard curves for each influenza HA strain, and independently calculating anti-HA IgG concentrations, allows for adjustment of influenza HA subtype variations in treatment group comparisons in clinical vaccine studies. This method facilitates the direct comparison of serum anti-HA IgG concentrations against different influenza HA subtypes for multiplex assays. Hindawi 2019-04-15 /pmc/articles/PMC6501432/ /pubmed/31178920 http://dx.doi.org/10.1155/2019/3053869 Text en Copyright © 2019 Dongmei Li et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Li, Dongmei
Wang, Jiong
Treanor, John J.
Zand, Martin S.
Improved Specificity and False Discovery Rates for Multiplex Analysis of Changes in Strain-Specific Anti-Influenza IgG
title Improved Specificity and False Discovery Rates for Multiplex Analysis of Changes in Strain-Specific Anti-Influenza IgG
title_full Improved Specificity and False Discovery Rates for Multiplex Analysis of Changes in Strain-Specific Anti-Influenza IgG
title_fullStr Improved Specificity and False Discovery Rates for Multiplex Analysis of Changes in Strain-Specific Anti-Influenza IgG
title_full_unstemmed Improved Specificity and False Discovery Rates for Multiplex Analysis of Changes in Strain-Specific Anti-Influenza IgG
title_short Improved Specificity and False Discovery Rates for Multiplex Analysis of Changes in Strain-Specific Anti-Influenza IgG
title_sort improved specificity and false discovery rates for multiplex analysis of changes in strain-specific anti-influenza igg
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501432/
https://www.ncbi.nlm.nih.gov/pubmed/31178920
http://dx.doi.org/10.1155/2019/3053869
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