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Updated: Jul 19, 2025

A Comparative Approach to Characterize the Landscape of Host-Pathogen Protein-Protein Interactions
Published on: July 18, 2013
Reconstructing multi-strain pathogen interactions from cross-sectional survey data via statistical network inference
Irene Man1,2, Elisa Benincà1, Mirjam E Kretzschmar2
1Centre for Infectious Disease Control, National Institute for Public Health and the Environment, Bilthoven, The Netherlands.
Abstract:
Infectious diseases often involve multiple pathogen species or multiple strains of the same pathogen. As such, knowledge of how different pathogens interact is key to understand and predict the outcome of interventions targeting only a subset of species or strains involved in disease. Population-level data may be useful to infer pathogen strain interactions, but most previously used inference methods only consider uniform interactions between all strains or focus on marginal pairwise interactions. As such, these methods are prone to bias induced by indirect interactions through other strains. Here, we evaluated statistical network inference for reconstructing heterogeneous interactions from cross-sectional surveys detecting joint presence/absence patterns of pathogen strains within hosts. We applied various network models to simulated survey data, representing endemic infection states of multiple pathogen strains with potential interactions in acquisition or clearance of infection. Satisfactory performance was demonstrated by the estimators converging to the true interactions. Accurate reconstruction of interaction networks was achieved by regularization or penalization for sample size. Although performance deteriorated in the presence of host heterogeneity, this was overcome by correcting for individual-level risk factors. Our work demonstrates how statistical network inference could prove useful for detecting multi-strain pathogen interactions and may have applications beyond epidemiology.
Insights
Understanding pathogen strain interactions is crucial for infectious disease control. This study shows statistical network inference can accurately map these complex, heterogeneous relationships from survey data.
Area of Science:
- Epidemiology
- Computational Biology
- Infectious Disease Dynamics
Background:
- Infectious diseases frequently involve multiple pathogen species or strains.
- Existing methods for inferring pathogen interactions are limited, often overlooking indirect effects and leading to biased results.
- Accurate understanding of pathogen interactions is vital for effective disease intervention strategies.
Purpose of the Study:
- To evaluate statistical network inference for reconstructing heterogeneous interactions among multiple pathogen strains.
- To assess the ability of these methods to detect joint presence/absence patterns of pathogen strains within hosts using cross-sectional survey data.
Main Methods:
- Applied various network models to simulated survey data representing endemic infection states with potential interactions.
- Investigated the impact of regularization and penalization techniques for sample size on interaction network reconstruction.
- Assessed the influence of host heterogeneity and explored corrections using individual-level risk factors.
Main Results:
- Statistical network inference estimators converged to true interactions, demonstrating satisfactory performance in simulations.
- Accurate reconstruction of complex interaction networks was achieved, particularly with regularization or penalization for sample size.
- Host heterogeneity impacted performance but was successfully overcome by correcting for individual-level risk factors.
Conclusions:
- Statistical network inference is a powerful tool for detecting multi-strain pathogen interactions from population-level survey data.
- The developed methods can accurately reconstruct heterogeneous interaction networks, accounting for indirect effects.
- This approach holds significant potential for improving epidemiological studies and informing targeted disease interventions.
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