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. 2021 Jun 29;9(7):751. doi: 10.3390/biomedicines9070751

Figure 4.

Figure 4

Networks analysis of SMCHD1-mutated cells reveals defects in cell signaling. Representative active modules sampled from the accumulated Pareto front of 30 runs for the different data sets using the MOGAMUN algorithm. The color of the edges (links) denotes the type of interaction/relationship between each pair of genes, specifically, protein–protein interactions (blue links), biological pathways (orange links), and correlation of expression data (yellow links). Upregulated nodes are colored in red and downregulated ones in green, the intensity of the color reflects the fold change. The black border reflects the level of significance (FDR < 0.05 and −2 > FC > 2). Genes corresponding to each node were analyzed using g:Profiler to define the corresponding molecular function and p-value. A large majority of nodes in BAMS and FSHD2 cells highlight changes in transmembrane receptor protein Tyrosine kinase signaling. Genes related to Tyrosine Kinase signaling: PIK3R1, PIK3R2, ERBB2, ERBB3, MET, EGF, EGFR, SHC1, SRC, VAV2, SYK, GAB1, CBL, LYN, EPHA2, CALM1, PLGC1, APP, AKL, PTPN11, SHC2, EPHA2, PLT1. (A–D) Representative nodes corresponding to Tyrosine Kinase signaling identified in BAMS NCSCs. (A) p-value = 3.3 × 10−18. (B) p-value = 3.3 × 10−18. (C) p-value = 1.3 × 10−19. (D) p-value = 1.3 × 10−7. (E–H) Representative nodes corresponding to Tyrosine Kinase signaling in FSHD2 NCSCs. (E) p-value = 1.14 × 10−17. (F) p-value = 2.4 × 10−18. (G) p-value = 8.5 × 10−15. (H) p-value = 1.14 × 10−15.