Fig. 4

The module–trait relationships by the WGCNA analysis of plasma-derived EV proteome data. (A) A heatmap illustrating Pearson correlations between eigenprotein expression levels of 9 WGCNA modules and the values of the sepsis-related traits of the plasma samples. The meanings of abbreviations for the traits in clinical lab data are as follows: BUN: blood urea nitrogen, Cr: creatinine, SOFA: sequential organ failure assessment, PLT: platelet count, INR: international normalized ratio, PTT: partial thromboplastin, PT: prothrombin time, WBC: White blood cell count, Hg: hemoglobin, Hct: hematocrit, K: potassium, and Na: sodium. The correlations were color-coded on a scale ranging from 1 (indicating a positive correlation, red) to -1 (indicating a negative correlation, blue). The size of each circle corresponds to the P value, while the color indicates the correlation value. (B, D, F, H, J, L) Relative eigenprotein abundances for the modules that showed a significant correlation with the sepsis diagnosis were shown on the box plots; M3 (B), M4 (D), M5 (F), M6 (H), and M7 (J). (L) Relative eigenprotein abundance for the M8 module that showed a significant correlation with the sepsis-related mortality was shown on the box plot. (C, E, G, I, K, M) MM-PS plots show the relationship between the module membership (MM) for each module and protein significance (PS) for sepsis diagnosis; M3 (C), M4 (E), M5 (G), M6 (I), and M7 (K). (M) MM-PS plots show the relationship between MM for M8 and PS for the sepsis-related mortality. The key driving proteins were marked by black arrows in the plots. An unpaired t-test was used for the statistical analysis of eigenprotein expression (*, P < 0.05; ***, P < 0.001; ****, P < 0.0001).