Exploring the temporal interplay of allergic sensitization and asthma via graph and manifold analysis.

Background: The association between allergic sensitization and asthma is well-documented, but its precise role in asthma remains uncertain. Component-resolved diagnostics allows detailed assessment of IgE-sensitization to multiple allergenic molecules (c-sIgE). We applied advanced network embedding techniques to investigate the dynamics of temporal development of multiple c-sIgE and identify networks associated with asthma.

Methods: In a population-based birth cohort, we measured c-sIgE to 112 proteins using multiplex array at 6 time points from infancy to adolescence. We built weighted co-occurrence networks between c-sIgEs to investigate connectivity structures at different ages. To identify critical periods where networks are similar/divergent, we applied graph embedding and dimensionality reduction techniques. We then compared network development structure between subjects with and without asthma at different ages and analyzed topological features to compare network structures.

Results: c-sIgE sensitization networks across ages revealed significant changes and a continuous evolution rather than abrupt shifts, with networks at ages 5 and 8 being very similar. Individuals with asthma consistently exhibited more complex and interconnected networks of c-sIgEs, which became more pronounced with age. Graph embedding showed that profiles of those with and without asthma were distinct and the separation persisted across ages. A specific set of c-sIgEs and their interactions were responsible for this distinction. Topological features of networks that distinguished between sensitized individuals with and without asthma were age-dependent.

Conclusions: The differences in c-sIgE networks between subjects with and without asthma are consistently observed throughout childhood. Age needs to be considered when developing interpretation algorithms for asthma diagnosis/prediction.