Systems Level Analysis of Systemic Sclerosis Shows a Network of Immune and Profibrotic Pathways Connected with Genetic Polymorphisms
Figure 2
Gene expression modules associated with the intrinsic subsets of SSc.
We identified 54 major sets of genes (modules) using WGCNA that define the spectrum of gene expression in SSc skin using Milano as a test case. The top 6 most significant modules are shown and each shows a statistically significant association with the intrinsic subsets (including the limited subset). Module assignment for each gene is unique. The genes that compose the subset-specific modules represent more than 40% of the protein-coding genes in the human genome. Therefore, the intrinsic subsets seem to be determined by a large fraction of the encoded genes. The module eigengene of each module is shown in a stem-plot below each heatmap with intrinsic subsets indicated by color above the heatmap. Proliferative, red; inflammatory, purple; limited, yellow; normal-like, green. (A) Inflammatory modules (p<10−9 and p<10−7; Kruskal-Wallis non-parametric ANOVA corrected for multiple testing), (B) Limited Module (p<0.006), (C) Fibroproliferative modules (p<10−7; p<10−8), (D) Fibroproliferative and Limited expression module (p<10−9). Enriched molecular processes are indicated for each subset to the right of each heat map.