Figure 3. Enrichment analysis of TPP-identified proteins as the targets of celecoxib in the rat hippocampus. This plot indicates enriched annotations related to disease, phenotypes, and biological pathways of celecoxib targeted proteins. Each panel distinctly represents the annotations of gene-disease associations (DisGeNET), Human Phenotype Ontology (HumanPhen), Mouse Genome Informatics (MGI), UKBiobank PheWeb, and WikiPathway.
In Figure 4, the enriched gene ontology annotations i.e., biological processes (BP), cellular components (CC), and molecular functions (MF) were summarized by using semantic similarity. The annotations of BP were divided into six major subsets (Fig. 4A). The SRPāˆ’dependent co-translational protein, targeting to membrane processes, contributes to the prominent concept in this analysis. This process is responsible for the targeting of proteins to the cell membrane during translation, and it is dependent on two key components, the signal-recognition particle (SRP) and the SRP receptor. Rab protein signal transduction is the second most prevalent annotation in the tree-map of BPs. Rab proteins represent the largest branch of the Ras-like small GTPase superfamily, alternating between GTP- and GDP-bound states and releasing a series of molecular signals within the cell. Nuclear-transcribed mRNA catabolism, nonsenseāˆ’mediated decay, post-translational protein modification, and neutrophil-mediated immunity are four other groups of annotations in BP similar to the result of pathway enrichment analysis. These terms indicate the long-term effects of Celecoxib by PTM-related mechanisms and G protein-related signaling pathways. At the molecular level, nine groups of MF annotations were illustrated for TPP-identified proteins (Fig. 4B). The activities related to signal transduction in neuronal cells involving transport mechanisms were also highlighted, such as myosin, actin, and cadherin binding, in addition to GDP binding and GTPase activity. The enriched annotations of CC are mainly corresponding to the cytosolic part, which also underscores altering the signaling pathways [59] (Fig. 4C).