Fig. 4: In-depth exploration of disease activity-related protein dynamics.

a Unsupervised k-means clustering analysis of DEPs across four disease activity groups (two-sided Student’s t test, p < 0.05). The expression patterns of disease-related proteins in distinct clusters are shown on the left, with enriched pathways (more than 5 proteins) for each cluster on the right (two-sided Fisher’s exact test). Box plots inside showing the median (center line), the 25th and 75th percentiles (bounds of box), and the minimum and maximum values (whiskers). b Heatmap visualizing protein trajectories across DAS28-CRP. The trajectories of 996 proteins are estimated using LOESS. c The number of DEPs across disease activity levels. DE-SWAN identified three local peaks at DAS28-CRP values of 3.1, 3.8, and 5.0. d Overlap of proteins with significant differential expression at the three local peaks. e Bubble plot visualizing the enriched pathways of significant proteins identified through linear regression with DAS28-CRP and at three peaks in DE-SWAN (two-sided Fisher’s exact test, p < 0.05). f Line plot visualizes the results of the linear regression analysis of proteins (significant at DAS28-CRP values of 3.1, 3.8, and 5.0 in DE-SWAN) with VAS, TJC, SJC, and CRP. The cumulative number of overlapped proteins that are significant either at DE-SWAN points or in relation to the four parameters is shown, with proteins ranked based on significance from the linear regression models (adjusted for age and sex, two-sided p value < 0.05). Source data are provided as a Source Data file.