Fig. 6

A network-based modular approach reveals common immune-mediated multi-omics processes during pregnancy. Overlapping differentially expressed genes (DEGs) and differentially methylated probes (DMPs) between the 3rd trimester and post-partum were characterized by changes in expression and methylation of opposite direction in these two time points in both women with MS and healthy controls (HC) and were thus termed shared rebound DEGs/DMPs. Modules were inferred from these shared rebound DEGs/DMPs using DIAMOnD and the PPI network (threshold >700). A KEGG pathway analysis of the module genes derived from RNA-seq, methylation data or the overlap between the modules derived from the two omics. Shown are the top 5 pathways, in terms of adjusted p-value, for at least one of the two groups (CD4⁺ and CD8⁺). All the pathways have an adjusted p-value ≤ 0.05; n is the total number of genes contained in the pathways of each column and gene ratio indicates the number of genes in a pathway divided by the total number of module genes. B Enrichment of the module genes for MS-associated genes retrieved from GWAS-derived MS genes and DisGeNET (all comparisons had p < 2.2e−16) in transcriptomics and methylomics of CD4⁺ and CD8⁺ T cells. The number of overlapping genes is shown above each bar. C The overlap between the genes derived from shared genes derived from the RNA-seq and methylation modules, termed rebound module, for each cell type, respectively, and the genes associated to the activated cells. Enrichment and overlaps were computed using Fisher’s exact test, p ≤ 0.05 was considered statistically significant.