Fig. 3: Integrative multi-omics analysis identified a transcriptionally altered fibroblast polarization in LYN-deficient cells perturbating predominantly cytokine- and matrix related pathways.
a Multi-omics profiling. Illustration was created with BioRender.com. b Spearman rank correlation analysis between T and S/P. Commonly expressed genes/proteins (52 in total) with absolute log2-FC > 0.8 were selected. c Integrative Reactome-Pathway Enrichment analysis. Weighted Voronoi Treemap (top) represents a hierarchal visualization of enriched top-level pathways (defined by single colors) enclosing sub-level pathways with the annotation of each enriched “omics”-layer. The proportional area matches the frequency and weight of this region per total. Grayscale plots (bottom) show statistical significance (FDR calculated by clusterProfiler80) for each sub-level pathway per “omics”-layer. d Heatmap of enriched GO-Terms independently performed per “omics”-layer, common terms displaying statistical significance (−log10 q value calculated by clusterProfiler80) are depicted. GO-terms are colored according to top-level pathways in (c). Bar plots represent total number of genes contributing to the enriched term (green: Molecular Function; gray: Biological Process). e Network visualization of Reactome-enrichment results: (i) Enrichment map of the top deregulated pathways in T, Tc, P, S. Each node represents one Reactome-Term, the circle colors indicate “omics”-layers in which the pathway was deregulated, circle size represents DEG number within this term. Edges represent shared genes between nodes, generated by clusterProfiler80. Domain annotation was added manually. (ii) STRING protein association network contributing to “ECM organization” Reactome-Pathway. Every node is divided in four segments (representing T, Tc, P, S) colored by the gene/protein log2-FC value. Gray color indicates missing values, asterisks indicate significant differentially expression in the respective layer (specified in Methods). Well-defined clusters of different ECM protein families were manually annotated. Only proteins with interaction score ≥ 0.9 are shown. f Gene Set Enrichment Analysis (GSEA) in T and Tc. Normalized enrichment scores (NES) of enriched genesets from the Hallmark Molecular Signatures Database are depicted. Colors represent “omics”-layers, dot size represents statistical significance as -log2 of adjusted p value (specified in Methods) of enriched terms. Genesets with negative NES were enriched in LYNWT, positive NES enriched in LYNKO clones. See also Fig. S2. Source data are provided as a Source Data file.
