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

Abstract

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. 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. 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. 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.