## 5 Microarray Results
### Gene Ontology and Gene Set Enrichment Analysis  
To further understand the results, we performed Gene Ontology using the Panther database ([[https://pantherdb.org/](https://pantherdb.org/)]([https://pantherdb.org/](https://pantherdb.org/))) by uploading both upregulated and downregulated genes and the results are provided in Figure 7A,B. The upregulated gene list identified total of 62 genes with 92 pathway hits. The top five pathways identified are the angiogenesis  
Figure 6: Selected critical networks in relation to (**A**) Cell Death and Survival, Cellular Compromise, Embryonic Development (Network 5), (**B**) Cellular Assembly and Organization, Cellular Movement, Hematological System Development and Function (Network 11), (**C**) Cardiovascular Disease, Congenital Heart Anomaly, Developmental Disorder (Network 12) and (**D**) Connective Tissue Development and Function, Embryonic Development, Organismal Development (Network 13). * Duplicates—Gene/Protein/Chemical identifiers marked with an asterisk indicate that multiple identifiers in the dataset file map to a single gene/chemical in the Global Molecular Network. signaling pathway, apoptosis signaling pathway, interleukin signaling pathway, integrin signaling pathway, and insulin signaling pathway with genes such as Fos, EGFRI, Itgb6, Irs1, Irs2, HSP1A, etc. (Figure 7A). The downregulated list of genes identified 43 pathway hits with 72 genes passing the criteria. The top five pathway identified by the downregulated list is Beta 1,2,3 adrenergic pathway, metabotropic glutamate receptor pathway III, etc., with key genes identified such as Grb3, Mmp8, Slc17a7, etc. Figure 7: _Cont._  
We also performed gene set enrichment analysis using ShinyGO 0.77 online software, version 0.77 ([[http://bioinformatics.sdstate.edu/go77/](http://bioinformatics.sdstate.edu/go77/)]([http://bioinformatics.sdstate.edu/go77/](http://bioinformatics.sdstate.edu/go77/))) with all differentially regulated genes with an FDR cutoff of 0.5, and the results of top 30 hits are shown in Figure 7C. The complete list with enrichment score is provided in Table S2. This analysis identified pathways such as the longevity-regulating pathway (Hspa8 Irs2 Irs1 Hspa1a), IL-17 signaling pathway (Fosb Fos Lcn2 Cxcl10), FoxO signaling pathway (Gadd45b Gadd45g Plk2 Irs2 Irs1 rs1), insulin resistance (Tbc1d4 Irs2 Irs1 Ppp1r3c), MAPK signaling pathway (Gadd45b Hspa8 Fos Gadd45g Myc Nr4a1 Hspa1a), etc. The enrichment FDR and fold enrichment scores are provided in Table 7. \begin{table}
\begin{tabular}{c c c c c c} \hline
**Enrichment FDR** & **nGenes** &
\begin{tabular}{c} **Pathway** \\ **Genes** \\ \end{tabular} & **Fold Enrichment** & **Pathway** & **Genes** \\ \hline
0.00656708 & 3 & 24 & 20.26388889 & Asthma & H2-Aa H2-Eb1 H2-Ab1 \\ \hline
3.24 \(\times\) 10\({}^{-7}\) & 9 & 80 & 18.2375 & \
\begin{tabular}{c} Antigen processing and presentation \\ \end{tabular} &
\begin{tabular}{c} Hspa8 Cd4 Cd74 H2-Aa H2-Eb1 H2-K1 H2-Q6 H2-Ab1 Hspa1a \\ \end{tabular} \\ \hline
0.000640951 & 5 & 53 & 15.29350105 & Allograft rejection & H2-Aa H2-Eb1 H2-K1 H2-Q6 H2-Ab1 \\ \hline
0.000640951 & 5 & 53 & 15.29350105 & Graft-versus-host disease & H2-Aa H2-Eb1 H2-K1 H2-Q6 H2-Ab1 \\ \hline \end{tabular}
\end{table} 
Table 7: Gene enrichment analysis. Figure 7: Venn diagram showing Panther pathway ontology analysis of both upregulated (**A**) and downregulated (**B**) genes. (**C**) Gene Ontology enrichment analysis using ShinyGO software. Figure shows the fold enrichment of the top 30 identified pathways.