TABLE III.
Most Significantly Pertinent Canonical Signal Transduction Pathways Predicted by IPA Based on the Differentially Expressed Genes in HPAH and IPAH vs Control
| Ingenuity Canonical Pathways | –log (P-value) | Ratio | Molecules |
|---|---|---|---|
| Mitotic roles of polo-like kinase | 6.04 | 1.08E-01 | KIF23,PLK4,CDC20,CCNB2,PLK1,PPP2R1B,CDK1,KIF11 |
| Salvage pathways of pyrimidine ribonucleotides | 3.12 | 5.31E-02 | DAPK1,NEK2,PLK1,TTK,CDK1,APOBEC3G |
| DNA damage-induced 14-3-3s signaling | 2.91 | 1.36E-01 | CCNE2,CCNB2,CDK1 |
| IL-6 signaling | 2.67 | 4.84E-02 | VEGFA,TNFAIP6,MAPK10,MAPK13,IL1R1,A2M |
| ATM signaling | 2.32 | 6.06E-02 | MAPK10,CCNB2,MAPK13, CDK1 |
| Inhibition of angiogenesis by TSP1 | 2.17 | 7.14E-02 | VEGFA,MAPK10,MAPK13 |
| Cyclins and cell cycle regulation | 1.88 | 4.17E-02 | CCNE2,CCNB2,PPP2R1B, CDK1 |
| Cell cycle: G2/M DNA damage checkpoint regulation | 1.86 | 6.12E-02 | CCNB2,PLK1,CDK1 |
| Role of CHK proteins in cell cycle checkpoint control | 1.61 | 5.08E-02 | PLK1,PPP2R1B,CDK1 |
| Role of JAK family kinases in IL-6-type cytokine signaling | 1.49 | 7.14E-02 | MAPK10,MAPK13 |
| IL-17A signaling in airway cells | 1.44 | 3.95E-02 | MAPK10,CCL20,MAPK13 |
| BMP signaling pathway | 1.25 | 3.49E-02 | BMP4,MAPK10,MAPK13 |
Canonical pathways analysis identified the pathways from the Ingenuity Pathways Analysis™ library of canonical pathways that were most significant to the dataset. The 227 selected genes in Supplementary Table S2 were associated with a canonical pathway in the ingenuity knowledge base were considered for analysis. The significance of the association between the dataset and the canonical pathway was determined as a P-value calculated by Fisher's exact test, a measure of the probability that the association between the proteins in the dataset and the canonical pathway is taking place by chance alone. The ratio is calculated as follows: number ofgenes in a given pathway that meet the cutoff criteria, divided by the total number of genes that make up that pathway and that are in the reference gene set. The molecules involved in those biological pathways were also listed in the table. The identity of those molecules can be retrieved from Supplementary Table S2. The full list of the predicted pathways was shown in Supplementary Table S4.