Table 3.
Summary of the most significant hallmark host responses in patients with PEDIS 4 when compared to PEDIS 3.
| NAME | Process category | Description | NES | FWER |
|---|---|---|---|---|
| Enriched host pathways in PEDIS 4 | ||||
| TNFA_SIGNALING_VIA_NFKB (TNF-alpha/nuclear factor kappa-light-chain-enhancer of activated B cells) | Signaling | Genes regulated by NF-kB in response to TNF | 1.9023656 | 0 |
| IL6_JAK_STAT3_SIGNALING (Interleukin 6/Janus kinase/signal transducers and activators for transcription | Signaling | Genes upregulated by IL6 via STAT3 e.g., during acute phase response | 1.7342762 | 0 |
| INFLAMMATORY_RESPONSE | Immune | Genes defining inflammatory response | 1.6779492 | 0 |
| PI3K_AKT_MTOR_SIGNALING (Phosphatidylinositide 3 kinases/Protein kinase B/mammalian target of rapamycin. | Signaling | Genes upregulated by activation of the PI3K/AKT/mTOR pathway, regulating cell proliferation, survival, and metabolism | 1.6093148 | 0.00 |
| HYPOXIA | Pathway | Genes upregulated in response to low oxygen levels | 1.5994961 | 0.00 |
| REACTIVE_OXIGEN_SPECIES | Pathway | Genes upregulated by reactive oxygen species (ROS) | 1.578071 | 0.00 |
| UV_RESPONSE | DNA damage | Genes upregulated in response to ultraviolet (UV) radiation | 1.5617301 | 0.01 |
| APOPTOSIS | Pathway | Genes mediating programmed cell death by activation of caspases | 1.5393971 | 0.01 |
| IL2_STAT5_SIGNALING (Interleukin 2/signal transducers and activators for transcription) | Signaling | Genes upregulated by STAT5 in response to IL2 stimulation | 1.5364993 | 0.02 |
| HEME_METABOLISM | Metabolic | Genes involved in metabolism of heme (a cofactor consisting of iron and porphyrin) and erythroblast differentiation | 1.534089 | 0.02 |
| HALLMARK_P53_PATHWAY (Tumor protein 53) | Proliferation | Genes involved in p53 pathways and networks in response to stress signals that impact upon cellular homeostatic mechanisms that monitor DNA replication, chromosome segregation, and cell division | 1.5275651 | 0.02 |
| ALLOGRAFT_REJECTION | Immune | Genes upregulated during transplant rejection/ alloimmune response to non-self-antigens expressed by donor tissues | 1.5268086 | 0.02 |
| MTORC1_SIGNALING (Mammalian target of rapamycin complex 1) | Signaling | Genes upregulated through activation of mTORC1 complex | 1.5246518 | 0.02 |
| Depleted host Pathways in PEDIS 4 | ||||
| NAME | Process category | Description | NES | FWER p-val |
| EPITHELIAL_MESENCHYMAL_TRANSITION | development | Genes defining epithelial–mesenchymal transition, as in wound healing, fibrosis, and metastasis | −1.9640744 | 0 |
| MYOGENESIS | development | Genes involved in development of skeletal muscle (myogenesis) | −1.6926087 | 0 |
The dataset was interrogated for pathway enrichment or depletion using the canonical pathways from the MsigDb collection using Gene Set Enrichment Analysis (GSEA). The GSEA pathway analysis results show host gene enrichment involving inflammatory, immune and signaling activation, and host gene depletion involving wound repair. NES: normalized enrichment score; FWER: family-wise error rate. Values in log fold change (logFC) column indicate fold change ranked from highest to lowest (p < 0.05, FWER < 0.05).