Table 3. Over-representation and pathway topology analysis using KEGG pathways terms.
The analysis is based on the molecular elements that constitute the interactome of CAD. Topology analysis is based on degree centrality, which measures the number of links that connects to a node within a pathway. Regulation trend (Trend) is based on differential expression of either *compounds, or **gene\proteins, or ***both. Down-regulation (↓), up-regulation (↑), contradictory regulation or not applicable (NA). General pathway association (class): fatty acids (FA), amino acids (AA), aminoacylation of transfer RNAs (AAcylation), signalling (SIG), energy metabolism (EMET), vitamin 5 as precursor (Vit5), disease (DIS), immune system (IMM), antioxidants (AntiOx), hormonal (HOR), and cytoskeleton (Cytosk). Gene-centric or metabolite-centric analysis (|).
| Pathway | Total | Hits | P.Value | Topology | Gene\compound | Class | Trend |
|---|---|---|---|---|---|---|---|
| Biosynthesis of unsaturated fatty acids|hsa01040 | 22 | 8 | 1.34E-07 | 0.38 | [Hexadecanoic acid, (9Z)-Octadecenoic acid, Linoleate, (8Z,11Z,14Z)-Icosatrienoic acid, Icosanoic acid, (9Z,12Z,15Z)-Octadecatrienoic acid, (4Z,7Z,10Z,13Z,16Z,19Z)-Docosahexaenoic acid, (7Z,10Z,13Z,16Z,19Z)-Docosa-7,10,13,16,19-pentaenoic acid, Icosadienoic acid] | FA | ↓* |
| Cysteine and methionine metabolism|hsa00270 | 34 | 6 | 6.16E-06 | 0.13 | [LDHAL6A, IL4I1, GSS, LDHA, LDHB, LDHC] | AA | NA |
| Aminoacyl-tRNA biosynthesis|hsa00970 | 46 | 8 | 6.17E-05 | 0.18 | [Glycine, L-Alanine, L-Arginine, L-Phenylalanine, L-Tyrosine, L-Histidine, L-Valine, L-Threonine] | AAcylation | ↓* |
| Pyruvate metabolism|hsa00620 | 41 | 5 | 2.42E-04 | 0.35 | [LDHAL6A, LDHA, LDHB, LDHC, LDHAL6B] | EMET | NA |
| PPAR signaling pathway|hsa03320 | 64 | 6 | 2.47E-04 | 1.13 | [SLC27A2, FABP1, APOA1, APOC3, PPARA, ADIPOQ] | SIG | ↓** |
| Phenylalanine metabolism|hsa00360 | 17|11 | 3|3 | 1.58E-03|4.31E-03 | 1.20|0.70 | [DDC, IL4I1, PAH], [L-Phenylalanine, L-Tyrosine, 2-Phenylacetamide] | AA | NA |
| Phenylalanine, tyrosine and tryptophan biosynthesis|hsa00400 | 5|4 | 2|3 | 1.91E-03|1.22E-04 | 2.33|2.67 | [IL4I1, PAH], [L-Phenylalanine, L-Tyrosine, 3-(4-Hydroxyphenyl)pyruvate] | AA | NA |
| Glycolysis / Gluconeogenesis|hsa00010 | 65 | 5 | 2.06E-03 | 0.06 | [LDHAL6A, LDHA, LDHB, LDHC, LDHAL6B] | EMET | NA |
| Pantothenate and CoA biosynthesis|hsa00770 | 18 | 4 | 2.06E-03 | 0.41 | [beta-Alanine, 3-Methyl-2-oxobutanoic acid, L-Valine, Acyl-carrier protein] | Vit5 | NA |
| Toll-like receptor signaling pathway|hsa04620 | 97 | 4 | 2.26E-03 | 0.41 | [TIRAP, LY96, IL6, MYD88] | SIG | NA |
| Fatty acid biosynthesis|hsa00061 | 6|43 | 2|4 | 2.83E-03|4.64E-02 | 3.42|0.24 | [FASN, OLAH], [Palmitoyl-CoA, Acyl-carrier protein, Hexadecanoic acid, (9Z)-Octadecenoic acid] | FA | ↓* |
| Fatty acid elongation|hsa00062 | 23 | 3 | 3.88E-03 | 0.03 | [FASN, OLAH, ACOT2, ACOT4] | FA | NA |
| Hypertrophic cardiomyopathy (HCM)|hsa05410 | 25 | 3 | 4.94E-03 | 0.88 | [IL6, ITGB3, ACTG1] | DIS | ↑** |
| Histidine metabolism|hsa00340 | 26|16 | 2|3 | 5.52E-03|1.31E-02 | 0.93|0.67 | [HDC, CNDP1], [L-Histidine, Carnosine, Histamine] | AA | ↓* |
| Complement and coagulation cascades|hsa04610 | 67 | 4 | 1.42E-02 | 0.11 | [FGA, SERPIND1, KNG1, VTN] | IMM | NA |
| Valine, leucine and isoleucine degradation|hsa00280 | 44 | 3 | 2.35E-02 | 0.17 | [IL4I1, BCAT1, BCAT2] | AA | NA |
| Valine, leucine and isoleucine biosynthesis|hsa00290 | 8 | 2 | 2.52E-02 | 0.29 | [2-Oxobutanoate, 3-Methyl-2-oxobutanoic acid] | AA | NA |
| Glutathione metabolism|hsa00480 | 46|26 | 3|5 | 2.64E-02|1.09E-03 | 0.77|0.70 | [GPX3, ANPEP, GSS], [Glycine, Glutathione, Glutathione disulfide, gamma-L-Glutamyl-L-cysteine, S-Substituted L-cysteine] | AntiOx | ↓*** |
| beta-Alanine metabolism|hsa00410 | 21 | 3 | 2.77E-02 | 0.85 | [beta-Alanine, L-Histidine, Carnosine] | AA | ↓* |
| Steroid hormone biosynthesis|hsa00140 | 81 | 7 | 3.53E-02 | 0.32099 | [DHEA, DHEA sulfate, pregnenolone sulfate, corticosterone, 11-Dehydrocorticosterone, cortisol, pregnenolone] | HOR | NA |
| Regulation of actin cytoskeleton|hsa04810 | 182 | 5 | 4.20E-02 | 0.4 | [CFL1, ITGAD, ITGB3, ACTG1, TMSB4X] | Cytosk | ↓** |
| Arginine and proline metabolism|hsa00330 | 56|45 | 3|4 | 4.37E-02|1.29E-02 | 0.54|0.45 | [GATM, NOS3, CNDP1], [L-Arginine, Nitric oxide, Guanidinoacetate, N(omega)-Hydroxyarginine] | AA | NA |