From: Analyzing the genes related to Alzheimer’s disease via a network and pathway-based approach
Pathway | p valueb | p BH valuec | Genes included in the pathwayd |
---|---|---|---|
Cytokines and inflammatory response | 1.03 × 10–9 | 8.79 × 10–8 | CXCL8, HLA-DRA, HLA-DRB1, IL10, IL12A, IL12B, IL1A, IL4, IL6, TGFB1, TNF |
cytokine network | 9.89 × 10–9 | 3.84 × 10–7 | CXCL8, IL10, IL12A, IL12B, IL18, IL1A, IL4, IL6, TNF |
Hematopoietic cell lineage | 1.92 × 10–7 | 5.46 × 10–6 | CD14, CD33, CD36, CD44, CR1, HLA-DRA, HLA-DRB1, HLA-DRB5, IL1A, IL1B, IL4, IL6, IL6R, MME, TNF |
Dendritic cells in regulating TH1 and TH2 Development | 3.11 × 10–7 | 8.29 × 10–6 | CD33, IL10, IL12A, IL12B, IL4, TLR2, TLR4, TLR9 |
Ovarian steroidogenesis | 5.88 × 10–6 | 1.09 × 10–4 | ALOX5, CYP19A1, FSHR, IGF1, INS, LDLR, LHCGR, PLA2G4A, PTGS2, STAR |
IL-5 signaling pathway | 9.00 × 10–6 | 1.60 × 10–4 | HLA-DRA, HLA-DRB1, IL1B, IL4, IL6 |
Neurotrophin signaling pathway | 1.08 × 10–5 | 1.77 × 10–4 | BDNF, CAMK2D, GSK3B, IRS1, NGF, NGFR, NTF3, NTRK1, NTRK2, PIK3R1, PSEN1, PSEN2, SOS2, TP53, TP73 |
HIF-1 signaling pathway | 1.12 × 10–5 | 1.77 × 10–4 | CAMK2D, EIF4EBP1, GAPDH, HMOX1, IGF1, IL6, IL6R, INS, NOS3, PIK3R1, RPS6KB2, TF, TLR4, VEGFA |
NOD-like receptor signaling pathway | 1.66 × 10–5 | 2.37 × 10–4 | CARD8, CCL2, CXCL8, IL18, IL1B, IL6, MEFV, NLRP1, NLRP3, TNF |
Mechanism of gene regulation by peroxisome proliferators via PPARα | 1.95 × 10–5 | 2.69 × 10–4 | APOA1, CD36, INS, LPL, PIK3R1, PPARA, PTGS2, RXRA, SP1, TNF |
Th1/Th2 differentiation | 2.54 × 10–5 | 3.19 × 10–4 | HLA-DRA, HLA-DRB1, IL12A, IL12B, IL18, IL4 |
Antigen-dependent B-cell activation | 2.68 × 10–5 | 3.26 × 10–4 | FAS, HLA-DRA, HLA-DRB1, IL10, IL4 |
Oxidative phosphorylation | 3.74 × 10–5 | 4.39 × 10–4 | COX10, COX15, MT-ATP6, MT-ATP8, MT-CO1, MT-CO2, MT-CO3, MT-CYB, MT-ND1, MT-ND2, MT-ND3, MT-ND4, MT-ND4L, MT-ND5, MT-ND6 |
PI3K-Akt signaling pathway | 3.80 × 10–5 | 4.39 × 10–4 | COL11A1, EFNA5, EIF4EBP1, FGF1, GNB3, GSK3B, IGF1, IL4, IL6, IL6R, INS, IRS1, NGF, NGFR, NOS3, PCK1, PIK3R1, PPP2R2B, RELN, RPS6KB2, RXRA, SOS2, TLR2, TLR4, TP53, VEGFA, YWHAQ |
NF-κB signaling pathway | 4.83 × 10–5 | 5.42 × 10–4 | CD14, CXCL8, ICAM1, IL1B, LCK, PARP1, PLAU, PTGS2, TLR4, TNF, TRAF2, UBE2I |
Phagosome | 7.77 × 10–5 | 8.29 × 10–4 | CD14, CD36, CTSS, HLA-A, HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB5, MBL2, MPO, NOS1, OLR1, RAB7A, TAP2, TLR2, TLR4 |
Erythrocyte differentiation pathway | 9.33 × 10–5 | 9.49 × 10–4 | CCL3, IGF1, IL1A, IL6, TGFB1 |
IL-10 anti-inflammatory signaling pathway | 1.82 × 10–4 | 1.69 × 10–3 | HMOX1, IL10, IL1A, IL6, TNF |
Cells and molecules involved in local acute inflammatory response | 1.82 × 10–4 | 1.69 × 10–3 | CXCL8, ICAM1, IL1A, IL6, TNF |
Toll-like receptor signaling pathway | 2.15 × 10–4 | 1.95 × 10–3 | CCL3, CD14, CXCL8, IL12A, IL12B, IL1B, IL6, PIK3R1, TLR2, TLR4, TLR9, TNF |
Free radical induced apoptosis | 2.22 × 10–4 | 1.97 × 10–3 | CXCL8, GPX1, SOD1, TNF |
Intestinal immune network for IgA production | 2.65 × 10–4 | 2.26 × 10–3 | HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB5, IL10, IL4, IL6, TGFB1 |
Selective expression of chemokine receptors during T-cell polarization | 3.35 × 10–4 | 2.68 × 10–3 | CCL3, CCR2, IL12A, IL12B, IL4, TGFB1 |
B lymphocyte cell surface molecules | 3.39 × 10–4 | 2.68 × 10–3 | CR1, HLA-DRA, HLA-DRB1, ICAM1 |
Phosphorylation of MEK1 by cdk5/p35 downregulates the MAP kinase pathway | 3.39 × 10–4 | 2.68 × 10–3 | CDK5, CDK5R1, NGF, NGFR |
Complement and coagulation cascades | 4.61 × 10–4 | 3.58 × 10–3 | A2M, C4A, C4B, CFH, CR1, F13A1, MBL2, PLAU, SERPINA1 |
ABC transporters | 5.87 × 10–4 | 4.32 × 10–3 | ABCA1, ABCA2, ABCA7, ABCC2, ABCG1, ABCG2, TAP2 |
Signal transduction through IL-1R | 6.97 × 10–4 | 5.05 × 10–3 | IL1A, IL1B, IL1RN, IL6, TGFB1, TNF |
mTOR signaling pathway | 8.19 × 10–4 | 5.83 × 10–3 | EIF4EBP1, IGF1, INS, IRS1, PIK3R1, RPS6KB2, TNF, VEGFA |
Adhesion and diapedesis of granulocytes | 9.49 × 10–4 | 6.65 × 10–3 | CXCL8, ICAM1, IL1A, TNF |
TNF signaling pathway | 1.12 × 10–3 | 7.69 × 10–3 | CCL2, FAS, ICAM1, IL1B, IL6, MAGI2, MMP3, PIK3R1, PTGS2, TNF, TRAF2 |
MAPK signaling pathway | 1.13 × 10–3 | 7.69 × 10–3 | BDNF, CD14, FAS, FGF1, IL1A, IL1B, MAPK8IP1, MAPT, MEF2C, NGF, NTF3, NTRK1, NTRK2, PLA2G4A, SOS2, TGFB1, TNF, TP53, TRAF2 |
The IGF-1 receptor and longevity | 1.26 × 10–3 | 8.28 × 10–3 | IGF1, PIK3R1, SOD1, SOD2 |
Glutathione metabolism | 1.45 × 10–3 | 8.95 × 10–3 | GPX1, GSTM1, GSTM3, GSTO1, GSTO2, GSTP1, GSTT1 |
Cytokine–cytokine receptor interaction | 1.48 × 10–3 | 8.95 × 10–3 | CCL2, CCL3, CCR2, CXCL8, FAS, IL10, IL12A, IL12B, IL18, IL1A, IL1B, IL23R, IL4, IL6, IL6R, NGFR, TGFB1, TNF, VEGFA |
Serotonergic synapse | 1.50 × 10–3 | 8.95 × 10–3 | ALOX5, APP, CYP2D6, GNB3, HTR2A, HTR6, KCNJ6, MAOA, PLA2G4A, PTGS2, SLC6A4 |
Antigen processing and presentation | 1.63 × 10–3 | 9.53 × 10–3 | CTSS, HLA-A, HLA-DQB1, HLA-DRA, HLA-DRB1, HLA-DRB5, HSPA5, TAP2, TNF |
Drug metabolism—cytochrome P450 | 1.88 × 10–3 | 1.05 × 10–2 | CYP2D6, GSTM1, GSTM3, GSTO1, GSTO2, GSTP1, GSTT1, MAOA |
Cell cycle: G1/S check point | 2.13 × 10–3 | 1.18 × 10–2 | CDK1, CDKN2A, GSK3B, TGFB1, TP53 |
Fcε RI signaling pathway | 2.26 × 10–3 | 1.23 × 10–2 | FCER1G, GAB2, IL4, INPP5D, PIK3R1, PLA2G4A, SOS2, TNF |
Apoptosis | 2.28 × 10–3 | 1.23 × 10–2 | FAS, IL1A, IL1B, NGF, NTRK1, PIK3R1, TNF, TP53, TRAF2 |
Role of Erk5 in neuronal survival | 2.61 × 10–3 | 1.39 × 10–2 | MEF2A, MEF2C, NTRK1, PIK3R1 |
Bioactive peptide-induced signaling pathway | 2.90 × 10–3 | 1.52 × 10–2 | CAMK2D, CDK5, GNA11, MAPT, MYLK, PTK2B |
Control of skeletal myogenesis by HDAC and calcium/calmodulin-dependent kinase (CaMK) | 2.93 × 10–3 | 1.52 × 10–2 | IGF1, INS, MEF2A, MEF2C, PIK3R1 |
Metabolism of xenobiotics by cytochrome P450 | 3.22 × 10–3 | 1.62 × 10–2 | CYP2D6, GSTM1, GSTM3, GSTO1, GSTO2, GSTP1, GSTT1, HSD11B1 |
Ras-independent pathway in NK cell-mediated cytotoxicity | 3.92 × 10–3 | 1.88 × 10–2 | HLA-A, IL18, PIK3R1, PTK2B |
Dopaminergic synapse | 4.48 × 10–3 | 2.11 × 10–2 | CAMK2D, CLOCK, COMT, DRD4, GNB3, GRIN2B, GSK3B, KCNJ6, MAOA, PPP2R2B, SLC6A3 |
Cholinergic synapse | 4.57 × 10–3 | 2.12 × 10–2 | CAMK2D, CHAT, CHRNA3, CHRNA4, CHRNA7, CHRNB2, GNA11, GNB3, KCNJ6, PIK3R1 |
The co-stimulatory signal during T-cell activation | 4.72 × 10–3 | 2.17 × 10–2 | HLA-DRA, HLA-DRB1, LCK, PIK3R1 |
Adhesion and diapedesis of lymphocytes | 5.03 × 10–3 | 2.28 × 10–2 | CXCL8, ICAM1, IL1A |
Notch signaling pathway | 5.07 × 10–3 | 2.28 × 10–2 | APH1A, APH1B, NCSTN, PSEN1, PSEN2, PSENEN |
Role of ERBB2 in signal transduction and oncology | 5.61 × 10–3 | 2.50 × 10–2 | ESR1, IL6, IL6R, PIK3R1 |
Aminoacyl-tRNA biosynthesis | 6.37 × 10–3 | 2.80 × 10–2 | MT-TG, MT-TH, MT-TL2, MT-TQ, MT-TR, MT-TS2, MT-TT |
Trka receptor signaling pathway | 6.55 × 10–3 | 2.80 × 10–2 | NGF, NTRK1, PIK3R1 |
Rac 1 cell motility signaling pathway | 6.62 × 10–3 | 2.80 × 10–2 | CDK5, CDK5R1, MYLK, PIK3R1 |
CTCF: first multivalent nuclear factor | 6.62 × 10–3 | 2.80 × 10–2 | CDKN2A, PIK3R1, TGFB1, TP53 |
Regulation of PGC-1a | 7.74 × 10–3 | 3.21 × 10–2 | CAMK2D, MEF2A, MEF2C, PPARA |
Calcium signaling pathway | 7.85 × 10–3 | 3.22 × 10–2 | ADRB1, ADRB2, ADRB3, CAMK2D, CHRNA7, GNA11, HTR2A, HTR6, LHCGR, MYLK, NOS1, NOS3, PTK2B |
Lck and Fyn tyrosine kinases in initiation of TCR activation | 8.30 × 10–3 | 3.38 × 10–2 | HLA-DRA, HLA-DRB1, LCK |
Adipocytokine signaling pathway | 8.75 × 10–3 | 3.52 × 10–2 | CD36, IRS1, PCK1, PPARA, RXRA, TNF, TRAF2 |
Ras signaling pathway | 9.43 × 10–3 | 3.76 × 10–2 | EFNA5, EXOC2, FGF1, GAB2, GNB3, GRIN2B, IGF1, INS, NGF, NGFR, PIK3R1, PLA2G3, PLA2G4A, SOS2, VEGFA |
Prolactin signaling pathway | 1.02 × 10–2 | 3.96 × 10–2 | ESR1, ESR2, GSK3B, INS, LHCGR, PIK3R1, SOS2 |
Catecholamine biosynthesis, tyrosine → dopamine → noradrenaline → adrenaline | 1.05 × 10–2 | 3.99 × 10–2 | DBH, PNMT |
Fat digestion and absorption | 1.14 × 10–2 | 4.32 × 10–2 | ABCA1, APOA1, APOA4, CD36, PLA2G3 |
Stress induction of HSP regulation | 1.26 × 10–2 | 4.63 × 10–2 | FAS, IL1A, TNF |
Regulation of hematopoiesis by cytokines | 1.26 × 10–2 | 4.63 × 10–2 | CXCL8, IL4, IL6 |
CTL-mediated immune response against target cells | 1.26 × 10–2 | 4.63 × 10–2 | FAS, HLA-A, ICAM1 |
Osteoclast differentiation | 1.32 × 10–2 | 4.81 × 10–2 | GAB2, IL1A, IL1B, LCK, PIK3R1, PPARG, TGFB1, TNF, TRAF2, TREM2 |