Table 1.
Annotation of gene clusters using Gene Ontology (GO), KEGG and Ingenuity databases
| Biological process GO terms 1 | KEGG pathways 2 | Ingenuity pathways 3 | |
| Cluster 1 |
Lipid metabolism SLC27A4 -LYPLA2-ENPP6-DGAT2L4-CYP51A1-FASN-SULT4A1-CPNE7-ANGPTL3-ACACA-LSS-ACLY-PBX1-PIGH-PLCL1-PRKAG3-PRKAA2-SCD -SBF2-PLA2G12B-MTMR3-PITPNM1 P = 5.E-04 |
Fatty acid biosynthesis ACLY-FASN-ACACA-SCD |
Fatty Acid Biosynthesis FASN-ACACA-MCCC2 P = 5.E-04 |
| 277 genes |
Lipid biosynthesis DGAT2L4-CYP51A1-FASN-ACACA-LSS-ACLY-PBX1-PIGH-PRKAG3-PRKAA2-SCD P = 2.E-03 Fatty acid biosynthesis FASN-ACACA-PRKAG3-PRKAA2-SCD P = 6.E-03 Regulation of action potential KCNMB2-SBF2-EIF2B4 P = 7.E-03 |
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Cluster 2 95 genes |
Lipid metabolism PECI-DCTN6-CPT1A-FABP1-ACSL1-ACAA1-HADHA-HMGCS1-APOB-ACOX1-SCP2-ADIPOR2-PLCZ1 P = 3.E-06 Fatty acid metabolism PECI-CPT1A-FABP1-ACSL1-ACAA1-HADHA-ACOX1-ADIPOR2 P = 2.E-07 Fatty acid oxidation CPT1A-HADHA-ACOX1-ADIPOR2 P = 4.E-06 Fatty acid beta-oxidation CPT1A-HADHA-ACOX1 P = 2.E-05 Energy derivation by oxidation of organic compounds FBP1-IDH1-PCK1-FBP2-GYG2 P = 8.E-03 Gluconeogenesis FBP1-PCK1-FBP2 P = 4.E-04 |
Fatty acid metabolism ACAT1-PECI-ACAA1-ACOX1-HADHA-ACSL1 PPAR signalling pathway PCK1-SCP2-FABP1-ACAA1-ACOX1-ACSL1 Synthesis and degradation of ketone bodies ACAT1-HMGCL-ACAA1-HMGCS1 Citrate cycle TCA cycle PCK1-ACAT1-HMGCL-IDH1-ACAA1 Gluconeogenesis PCK1-ACAT1-HMGCL-FBP1 Valine.leucine and isoleucine degradation ACAT1-HMGCL-ACAA1-HADHA-HMGCS1 Lysine degradation ACAT1-BBOX1-HADHA |
Fatty Acid Metabolism CYP3A43-CYP4A22-CPT1A-ACAA1-CYP2C18-ACOX1-PECI-ACAT1-ACSL1-HADHA P = 2.E-11 Synthesis and Degradation of Ketone Bodies 1-06E01 6-42E-02 CYP3A43-CYP4A22-CPT1A-ACAA1-CYP2C18-ACOX1-PECI-CPT2-ACAT1-EHHADH-ACSL1-HADHA ACAA1-ACAT1-HMGCL-HMGCS1-HADHA P = 2.E-11 Pyruvate Metabolism ACAA1-ACAT1-PCK1-ACSL1-HADHA P = 2.E-05 Valine- Leucine and Isoleucine Degradation ACAA1-ACAT1-HMGCL-HMGCS1-HADHA P = 9.E-08 6-94E00 6-54E-02 ACAA1-ACAT1-HMGCL-HMGCS2-EHHADH-HMGCS1-HADHA Lysine Degradation BBOX1-ACAA1-ACAT1-MLL3-HADHA P = 1.E-06 Tryptophan Metabolism CYP3A43-CYP4A22-ACAA1-CYP2C18-ACAT1-HADHA P = 8.E-06 Propanoate Metabolism ACAA1-ACAT1-ACSL1-HADHA P = 1.E-05 1-36E00 2-02E-02 EHHADH-HADHA 8-54E-01 1-69E-02 PCK1-IGFBP1 |
|
Cluster 3 517 genes |
Cell cycle MPHOSPH9-TRIM13-TADA3L-YWHAQ-ESCO2-DBC1-E2F6-ERN1-FGF6-SH3BP4-FRAP1-GAS2-APBB2-KRAS-MAD2L1-MDM2-MLH1-MUTYH-NRAS-NDE1-PPP1CB-CDC37L1-PBK-PRKG2-PTMS-BARD1-CLSPN-NEK4-YWHAH-MAD1L1-MCM8-CCNH-PRC1-MTSS1-CUL7-DCLRE1A-CDC34 P = 9.E-03 Glycolysis DLAT-ENO1-OGDH-PGAM1-PKM2-UEVLD P = 8.E-03 Cytokinesis CECR2-PRC1-ROCK2 P = 7.E-03 Ceramide metabolism GALC-PRKAA1-SGPL1 P = 7.E-03 Regulation of protein catabolism ATE1-MDM2-BARD1 P = 2.E-03 |
Insulin signalling pathway PTPN1-PRKAA1-KRAS-FRAP1-PRKAB1-SORBS1-CRK-NRAS ErbB signalling pathway_ CAMK2A-JUN-KRAS-FRAP1-PAK7-SRC-CRK-NRAS- GnRH signalling pathway CAMK2A-ADCY3-JUN-KRAS-CACNA1C-SRC-NRAS Renal cell carcinoma_ JUN-SLC2A1-KRAS-PAK7-ARNT-CRK-NRAS-EGLN3 Tight junction_ JAM3-KRAS-CLDN16-SRC-MAGI1-NRAS-ACTB Glioma_ CAMK2A-KRAS-FRAP1-MDM2-NRAS |
Chemokine Signaling ROCK2-SRC-PLCB4-CAMK2A-NRAS-JUN-MYL2-PPP1CB-KRAS P = 3.E-04 Ephrin Receptor Signaling MAP3K14-SRC-NRAS-CREB3-SOS2-KRAS-CRK-ROCK2-AKT1-SORBS1-EFNB1-ACP1-ARPC4-PRKAA1-PAK7-MAK P = 6.E-04 B Cell Receptor Signaling MAP3K14-FRAP1-AKT1-CAMK2A-NRAS-JUN-MAP3K7-CREB3-SOS2-PIK3AP1-KRAS P = 3.E-03 Estrogen Receptor Signaling SRC-PRKDC-CCNH-NRAS-SOS2-KRAS-GTF2A1-MED4-ESR2 P = 3.E-03 PDGF Signaling SRC-NRAS-JUN-ACP1-SOS2-KRAS-CRK P = 4.E-03 Wnt/Î2-catenin Signaling SRC-AKT1-WIF1-MAP3K7-WNT7B-FZD3-DKK2-MDM2 (includes EG:4193)-WNT5B-WNT2-SOX5 (includes EG:6660) P = 6.E-03 Actin Cytoskeleton Signaling ABI2-TIAM1-NRAS-MYL2-ACTB-SOS2-PPP1CB-KRAS-CRK-FGF6-ROCK2-ARPC4-PRKAA1-PAK7-MAK P = 6.E-03 JAK/Stat Signaling FRAP1-AKT1-NRAS-SOS2-PTPN1-KRAS P = 8.E-03 Hypoxia Signaling in the Cardiovascular System AKT1-JUN-COPS5-CREB3-MDM2 (includes EG:4193)-CDC34-UBE2I-ARNT P = 6.E-04 |
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Cluster 4 273 genes |
TGF.beta signalling pathway ACVR2A-PPP2R2A-RBL1 Complement and coagulation cascades F13A1-C8B-F8-PLAU Purine metabolism ADSL-ITPA-ATIC-POLR1B-POLR3G-POLR2C Gap junction CDC2-PDGFA-MAP2K2-GNAI1 RNA_polymerase POLR1B-POLR3G-POLR2C Histidine_metabolism ADSL-GAD1-ATIC Long.term depression RARB-CASP9-STK4-MAP2K2 Long.term_potentiation GRIN2B-GRIN2A-MAP2K2 |
cAMP-mediated Signaling CNGA4-MAP2K2-GNAO1-GNAI1-HTR1A-RGS12-CNGA1-CHRM3-CHRM5 P = 1.E-03 1–69°00 6–67°-02 HDAC4-TGFB3-RBL1-SIN3A Ephrin Receptor Signaling GRIN2B-GRIN2A-MAP2K2-PDGFA-CXCL12-GNAO1-ITGA2-GNAI1-ARPC3-CDC2-ACVR2A P = 1.E-03 1–26°00 3–64°-02 SOX9-GNAO1-RARB-TGFB3-SFRP5-ACVR2A |
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The pathways sub-lined were found in at least two of the three analyses.1 Biological process GO terms obtained by the Gene Ontology Tree Machine software (GOTM). Are only indicated the enriched biological process GO terms with a significant level of pvalue < 0.01 (see Methods) and a minimum of 3 genes associated. 2 Kegg pathways: are only indicated those with a minimum of 3 genes associated and having a probability to be observed in the cluster 4-fold superior than the probability to obtain it by chance.3 Ingenuity pathways: are indicated the top five Canonical pathways associated to each cluster (pvalue < 0.01). Only canonical pathways with at least 3 genes affiliated were conserved.