Table 1 Pathways enriched in Alzgset^a

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