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 SRPādependent
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, nonsenseāmediated 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).