Figure 4.
Integration of miRNA, and cytokine and chemokine signatures
(A) Score plots for the first two latent variables from PLSR obtained using cytokine and chemokine data together with DE miRNA measurements. The plot on the left was obtained using all three severity levels (mild, moderate, and severe), whereas that on the right was obtained using only two classes (severe and mild/moderate).
(B) Results from PLSR with patients considered in two groups for different datasets with continuous output values assigned to the nearest discrete class number. Accuracies shown were obtained using leave-one-patient-out cross validation, using only cytokine and chemokine (CC) values, all miRNA values, only DE miRNAs values, or combining all CC values with DE miRNAs.
(C) Example scatterplots showing strong, severity group-specific correlations in mild (green), moderate (blue), or severe (magenta) patients.
(D) Number of miRNAs (Y axis) in the top 5 strongest correlations with 1, 2, 3, 4, 5, 6, or over 6 cytokines/chemokines per severity group. See Table S4
(E) Spearman correlation coefficients for top 5 correlated miRNAs with IL6 and CCL20 in mild (green), moderate (blue), and severe (magenta) groups.
(F) As in E, but for CCL17, CXCL10, and CCL5.
(G) Canonical correlation analysis (CCA) to relate the miRNAs associated with cell death in the severe group (Figure 1E) with cytokines and chemokines. Cytokines/chemokines with individual absolute correlation greater than 0.4 (for the severe group) with any of these miRNAs were included in the analysis. The canonical scores plot shows data (from individual samples) for the12 patients used to determine the canonical covariates (c.c. = 0.8, p = 4.8 × 10−6) in black. The coefficients obtained are shown in the table and are used to obtain the canonical scores for 5 randomly chosen patients reserved as an independent test set (plotted in red).