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A flexible class of latent variable models for the analysis of antibody response data

Giorgi, Emanuele and Wallin, Jonas LU (2026) In Biostatistics 27(1).
Abstract

Summary: Existing approaches to modelling antibody concentration data are mostly based on finite mixture models that rely on the assumption that individuals can be divided into 2 distinct groups: seronegative and seropositive. Here, we challenge this dichotomous modelling assumption and propose a latent variable modelling framework in which the immune status of each individual is represented along a continuum of latent seroreactivity, ranging from minimal to strong immune activation. This formulation provides greater flexibility in capturing age-related changes in antibody distributions while preserving the full information content of quantitative measurements. We show that the proposed class of models can accommodate a large variety of... (More)

Summary: Existing approaches to modelling antibody concentration data are mostly based on finite mixture models that rely on the assumption that individuals can be divided into 2 distinct groups: seronegative and seropositive. Here, we challenge this dichotomous modelling assumption and propose a latent variable modelling framework in which the immune status of each individual is represented along a continuum of latent seroreactivity, ranging from minimal to strong immune activation. This formulation provides greater flexibility in capturing age-related changes in antibody distributions while preserving the full information content of quantitative measurements. We show that the proposed class of models can accommodate a large variety of model formulations, both mechanistic and regression-based, and also includes finite mixture models as a special case. We also propose a computationally efficient (Formula presented) -based estimator as an alternative to maximum likelihood estimation, which substantially reduces computational cost, and we establish its consistency. Through a case study on malaria serology, we demonstrate how the flexibility of the novel framework enables joint analyses across all ages while accounting for changes in transmission patterns. We conclude by outlining extensions of the proposed modelling framework and its relevance to other omics applications.

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author
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
age-dependency, antibody dynamics, immunology, latent variable models, malaria, mixture models, serology
in
Biostatistics
volume
27
issue
1
publisher
Oxford University Press
external identifiers
  • pmid:42086482
  • scopus:105037791700
ISSN
1465-4644
DOI
10.1093/biostatistics/kxag008
language
English
LU publication?
yes
id
96d00429-53da-408a-bdea-fb0b971d077f
date added to LUP
2026-07-07 15:41:04
date last changed
2026-09-15 21:23:50
@article{96d00429-53da-408a-bdea-fb0b971d077f,
  abstract     = {{<p>Summary: Existing approaches to modelling antibody concentration data are mostly based on finite mixture models that rely on the assumption that individuals can be divided into 2 distinct groups: seronegative and seropositive. Here, we challenge this dichotomous modelling assumption and propose a latent variable modelling framework in which the immune status of each individual is represented along a continuum of latent seroreactivity, ranging from minimal to strong immune activation. This formulation provides greater flexibility in capturing age-related changes in antibody distributions while preserving the full information content of quantitative measurements. We show that the proposed class of models can accommodate a large variety of model formulations, both mechanistic and regression-based, and also includes finite mixture models as a special case. We also propose a computationally efficient (Formula presented) -based estimator as an alternative to maximum likelihood estimation, which substantially reduces computational cost, and we establish its consistency. Through a case study on malaria serology, we demonstrate how the flexibility of the novel framework enables joint analyses across all ages while accounting for changes in transmission patterns. We conclude by outlining extensions of the proposed modelling framework and its relevance to other omics applications.</p>}},
  author       = {{Giorgi, Emanuele and Wallin, Jonas}},
  issn         = {{1465-4644}},
  keywords     = {{age-dependency; antibody dynamics; immunology; latent variable models; malaria; mixture models; serology}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Oxford University Press}},
  series       = {{Biostatistics}},
  title        = {{A flexible class of latent variable models for the analysis of antibody response data}},
  url          = {{http://dx.doi.org/10.1093/biostatistics/kxag008}},
  doi          = {{10.1093/biostatistics/kxag008}},
  volume       = {{27}},
  year         = {{2026}},
}