## 3 Results
### Functional Annotation of the DEGs
#### 3.3.2 Functional Annotation of the Globally Up-Regulated Genes  
Similarly, we assessed the functional annotation of the globally up-regulated genes across all UBC samples and found that the DEGs participate in protein binding, in terms of their molecular function. In addition, they are related to the proteasome (Figure 9A, Table 3). These findings were confirmed by the pathway annotation analysis, where the DEGs manifested participation in the proteasome and cell cycle pathways, but also in base excision repair, DNA replication, N-glycan biosynthesis, and cell cycle and Epstein - Barr virus infection, among others (Figure 9B). Finally, the investigation of drug annotation showed that DEGs were related to Pyridone 6, 1D-myo-inositol 1,4,5-triphosphate, Tofacitinib, Inositol 1,3,4,5-tetrakisphosphate, S-2(-Hydroxyethyl) Thiocysteine, Formic Acid, Liothyronine, Phenethyl Isothiocyanate, Dasatinib and Medical Cannabis (Figure 9C).  
Figure 8: Pathway annotation (**A**) and drug annotation (**B**) of the globally down-regulated DEGs (Legend: ER: enrichment ratio, FDR: false discovery ratio).  
Figure 9: Functional annotation of the globally up-regulated DEGs in UBC. The annotation analysis includes gene ontology (GO) enrichment (**A**), pathway analysis (**B**), and drug annotation (**C**) (Legend: MF: molecular function, BP: biological process, CC: cellular component, KEGG: KEGG pathway database, REAC: reactome pathway database, WP: Wikipathways, TF: transcription factor-binding motifs, MIRNA: MiRNA targets, HPA: he Human Protein Atlas, CORUM: The Comprehensive Resource of Mammalian Protein Complexes, HP: human phenotype ontology).  
\begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**ID** & **Source** & **Term** & **Term ID** & \(P_{adj}\) & **Genes** \\ \hline  & & & & YES1,PMM1,CDC20,IR73,MCM5,ARL6 IP1,CYTH2,LASP1,PSMD2, \\
1 & COMMF & protein binding & GO:0005515 & 0.0009515 & PSMMD2,SDMC3,SDMC4,PAL3,STMN1,ADRR1,HMGA1,FPN1,TNN, \\  & & & & YES2,UX,GEN2,R12,G2,FPCNA,A,PTMA,SNBP,USP7,VDAC1, \\  & & & & YWHAB,APOBEC3B,KKT14 \\ \hline
2 & COMMF &
\begin{tabular}{c} delibyl-diphosphologosaccharide-protein \\ glyotransferase activity \\ \end{tabular} & GO:0004579 & 0.019061 & DOOST,RPN1 \\ \hline
3 & COMMF & oligosaccharidesary transferase activity & GO:0004576 & 0.025388 & DOOST,RPN1 \\ \hline
4 & COMMF & protein-containing complex binding & GO:0004877 & 0.044508 & CDC20,LASP1,ADR1,UNG,PCNA,SNRP,VDAC1,VHHAB,KKT14 \\ \hline  & & & viral process & GO:0016032 & 0.021014 & IRJ3,JHGA1,UNG,GJER2,PCNA,USP7,VDAC1,VHHAB,APOBEC3B \\ \hline
5 & & & & 1 RJ3,P3,P3 MD2,PSMD2,STMN1,HMGA1,TYK2,UNG,K2F6,PCNA,USP7, \\ \hline  & & & & YES1,YMD2,PSMD2,STMN1,HMGA1,TYK2,UNG,K2F6,PCNA,USP7,VDAC1,VHHAB,APOBEC3B \\ \hline
6 & COMMF & symbiotic process & GO:0044403 & 0.034472 & IRJ3,JHGA1,UNG,GJER2,PCNA,USP7,VDAC1,VHHAB,APOBEC3B \\ \hline
7 & GOCC & proteasome regulatory particle & GO:000588 & 0.001241 & PSMMD2,PSMD2,SDM2, \\ \hline  & & & YES1,PMM1,CDC20,IRJ3,MCM5,ARL6 IP1,CYTH2,PSMD2,PSMD2, \\
8 & & & & 0.0005829 & 0.001839 & STMN1,ARM1,HMGA1,FPN1,TNN,TYK2,PIM,SNRP,USP7, \\  & & & & YWHAB,KKT14 \\ \hline  & & & & &  
\begin{tabular}{c c c c c c} \multicolumn{6}{c}{Table 3. Cont.} \\ \hline
**ID** & **Source** & **Term** & **Term ID** & **P\({}_{all}\)** & **Genes** \\ \hline \multirow{2}{*}{14} & \multirow{2}{*}{GOCC} & \multirow{2}{*}{intracellular membrane-bounded organelle} & & YES1,CC20,IRF3,MCM5,AR16 IP,CYTH2,PSMD2,PSMD2,PSMD2,PDOST, \\  & & & CO043231 & 0.043905 & NDUVF2,RAIJ,ADRM,JIMG4,RPN1,TN,TYX2,UNG,EBNA1 BP2, \\  & & & & Kf2R,PCAN,YTH2,ANSRPR,US27,YDAC1,NPHIA,APOREC3B,KKT14 \\ \hline
15 & KEGG & Protelsome & KEGG,003050 & 0.022187 & PSMM2,PSMD2,ADRM \\ \hline
16 & KEGG & Cell cycle & KEGG,04110 & 0.031652 & CDC20,MCM5,PCNA,YWHAB \\ \hline
17 & REAC & Ub-specific processing proteases & REAC-RFA-5698880 & 0.002821 & CDC20,PSMD2,PSMD7,ADBMIM,US27,YDAC1 \\ \hline
18 & WP & Cell Cycle & WP-WP179 & 0.029044 & CDC20,MCM5,PCNA,YWHAB \\ \hline \end{tabular}