Figure 3.

Sputum transcriptome network analysis identifies a type 2 (T2) inflammation network that clusters subjects with T2-high, T2-ultrahigh, and T2-low asthma. (A, B) Eigengene values of the dark green network were robustly increased in subjects with asthma (black) compared with healthy control subjects (light gray) and were associated with lower FEV₁ values. (C) A summary metric of IL-4, IL-5, and IL-13 airway T2 gene expression (T2 gene mean) was strongly associated with the dark green network eigengene values. (D) Hierarchical clustering of subjects based on expression of genes in the dark green network resulted in three primary clusters. Cluster 1 was characterized by low T2 gene expression and contained an equal distribution of subjects with asthma (n = 35) and healthy control subjects (n = 25). Cluster 2 was characterized by high T2 gene expression and consisted predominately of subjects with asthma (n = 34) and few healthy control subjects (n = 2). Cluster 3 was characterized by extremely high T2 gene expression (T2-ultrahigh) and was comprised exclusively of subjects with asthma (n = 15). Black network eigengene values strongly correlated with dark green network eigengene values. (E) The T2 gene mean was robustly higher in subjects with T2-ultrahigh asthma. (F) Subjects with T2-ultrahigh asthma are characterized by older age. ICS = inhaled corticosteroids.