Table 2. Ingenuity pathway analysis using genes differentially expressed in hippocampi of alcoholics.
Pathways in Section A are common to genes identified in multiple studies. Section B lists pathways identified only in this study.
| Canonical Pathways | p value | Significant genes in the pathway |
|---|---|---|
| A. Pathways common to multiple studies | ||
| Acute Phase Response Signaling |
1.1E-04 |
SOCS3, TCF4, SERPING1,
TNFRSF1A MAP3K1, VWF, SERPINA3, IL1R1, NR3C1 TRAF6, C1R, AKT1, TF, CFB, MAP2K3, OSMR |
| Aldosterone Signaling in Epithelial Cells |
1.1E-04 |
HSPA1A/HSPA1B, HSPH1, SLC12A2,
DNAJA1 HSPA5, HSPA1L, PLCD1, HSPA8, HSPE1 HSP90AA1, HSPB7, DNAJB6, PLCD4, PRKD1 ATM |
| Axonal Guidance Signaling | 2.1E-02 |
PXN, PAPPA, C9orf3, GNAI1, DPYSL5,
SLIT2 ADAMTS9, TUBA1B, PLCD1, SEMA6D, AKT1 GNB2, ADAM10, RTN4, GNG5, ERBB2 SEMA4B, PLCD4, MYL3, FARP2, PRKD1, ATM |
| Cell Cycle: G1/S
Checkpoint Regulation |
4.9E-02 | HDAC9, CCND3, PAK1IP1, CCND1, ATM |
| CXCR4 Signaling | 2.6E-02 |
PXN, AKT1, RHOB, RHOC, GNB2,
GNAI1 GNG5, MYL3, PRKD1, ATM |
| Cyclins and Cell Cycle Regulation |
4.4E-02 |
CCNA2, HDAC9, CCNA1, CCND3,
CCND1 ATM |
| EIF2 Signaling | 2.8E-05 |
RPL24, RPS2, RPL23A,
RPS17/RPS17L RPLP0, RPL7, RPL10A, RPL35, RPS3A, AKT1 RPL7A, RPL39, RPL19, RPL12, RPS5, RPL29 ATM, RPSA |
| Estrogen-mediated S-phase Entry |
4.1E-02 | CCNA2, CCNA1, CCND1 |
| Glioma Invasiveness Signaling | 3.8E-02 | TIMP4, RHOB, TIMP1, RHOC, ATM |
| HGF Signaling | 4.2E-02 |
PXN, AKT1, MAP3K6, MAP3K1,
CCND1 PRKD1, ATM |
| ILK Signaling | 4.0E-02 |
PXN, CDH1, AKT1, RHOB, TNFRSF1A,
RHOC CREB1, ITGB4, CCND1, MYL3, ATM |
| Inhibition of
Matrix Metalloproteases |
7.9E-03 | TIMP4, TIMP1, THBS2, ADAM10, MMP24 |
| mTOR Signaling | 3.5E-03 |
NAPEPLD, DDIT4, RHOC, RPS2,
PRR5L RPS17/RPS17L, PLD1, AKT1, RPS3A, RHOB RPS5, PRKD1, ATM, RPSA |
| p70S6K Signaling | 4.0E-02 |
PLCD1, IL4R, AKT1, GNAI1, PLCD4,
PLD1 PRKD1, ATM |
| Protein Ubiquitination Pathway | 1.8E-02 |
USP28, MED20, HSPA1A/HSPA1B,
HSPH1 USP19, DNAJA1, HSPA5, HSPA1L, HSPA8 TRAF6, UBE2G1, HSPE1, HSP90AA1, HSPB7 DNAJB6 |
| Reelin Signaling in Neurons | 4.2E-02 |
AKT1, ARHGEF2, PAFAH1B1, VLDLR,
ATM APP |
| RhoGDI Signaling | 2.4E-02 |
CDH1, PPP1R12C, RHOB, RHOC,
GNB2 GNAI1, GNG5, ARHGEF17, ARHGEF2, DLC1 MYL3 |
| Role of Macrophages, Fibroblasts and Endothelial Cells in Rheumatoid Arthritis |
3.8E-02 |
SOCS3, TCF4, IL1RL1, TNFRSF1A,
CEBPD IL1R1, CCND1, PLCD1, TRAF6, AKT1, CREB1 MAP2K3, PLCD4, PRKD1, TCF7L2, ATM |
| Signaling by Rho Family GTPases |
7.6E-03 |
SEPT8, PPP1R12C, RHOC, SEPT7,
GNAI1 ARHGEF17, PLD1, CDH1, RHOB, GNB2 GNG5, ARHGEF2, PARD3, MYL3, ATM |
| TR/RXR Activation | 1.9E-02 |
KLF9, AKT1, NXPH2, ACACA,
THRA TBL1XR1, ATM |
| Type II Diabetes
Mellitus Signaling |
3.4E-02 |
SOCS3, AKT1, TNFRSF1A, MAP3K1,
ACSL5 SLC27A3, PRKD1, ATM |
| B. Additional significant pathways | ||
| Activation of IRF by Cytosolic Pattern Recognition Receptors |
1.5E-02 | DHX58, IFIH1, TRAF6, ZBP1, IKBKAP, IFIT2 |
| Acute Myeloid Leukemia Signaling |
1.2E-02 |
TCF4, AKT1, CCNA1, MAP2K3,
CCND1 TCF7L2, ATM |
| Aryl Hydrocarbon
Receptor Signaling |
1.9E-03 |
TGM2, ALDH4A1, CCNA2, ALDH1L1,
CCNA1 CCND3, HSP90AA1, HSPB7, DHFR, CCND1 PTGES3, ATM |
| ATM Signaling | 4.4E-02 | MDM4, GADD45A, CREB1, BLM, ATM |
| Biotin-carboxyl Carrier
Protein Assembly |
5.9E-03 | ACACB, ACACA |
| Cardiac Hypertrophy Signaling | 1.4E-02 |
MAP3K6, RHOC, MAP3K1, GNAI1,
PLCD1 AKT1, RHOB, CREB1, GNB2, GNG5, MAP2K3 PLCD4, MYL3, ATM |
| Colorectal Cancer
Metastasis Signaling |
4.9E-02 |
TCF4, TNFRSF1A, RHOC, CCND1,
MMP24 CDH1, AKT1, MSH2, RHOB, GNB2, GNG5 TCF7L2, ATM |
| Complement System | 2.0E-02 | C1R, SERPING1, CD59, CFB |
| Endometrial Cancer Signaling | 2.5E-02 | CDH1, AKT1, ERBB2, CCND1, ATM |
| eNOS Signaling | 9.8E-03 |
HSPA8, CCNA2, AKT1,
CCNA1 HSPA1A/HSPA1B, HSP90AA1, HSPA5 NOSTRIN, HSPA1L, ATM |
| GADD45 Signaling | 3.4E-03 | GADD45A, CCND3, CCND1, ATM |
| Germ Cell-Sertoli Cell
Junction Signaling |
4.6E-03 |
PXN, CDH1, AKT1, MAP3K6,
RHOB TNFRSF1A, RHOC, MAP3K1, MTMR2 MAP2K3, TUBA1B, ATM |
| Glucocorticoid Receptor Signaling |
4.7E-03 |
HSPA1A/HSPA1B, MAP3K1, HSPA5,
CD163 NR3C1, TAF13, TSC22D3, PTGES3, HSPA1L HSPA8, TRAF6, AKT1, CREB1, FKBP4 HSP90AA1, FKBP5, ATM |
| HER-2 Signaling in Breast Cancer |
1.1E-02 |
AKT1, ITGB4, ERBB2, PARD3,
CCND1 PRKD1, ATM |
| Hereditary Breast Cancer Signaling |
3.4E-02 |
HDAC9, AKT1, MSH2, GADD45A,
BLM CCND1, FANCL, ATM |
| HIF1α Signaling | 4.8E-02 |
EGLN2, AKT1, EDN1, MAPK4,
HSP90AA1 MMP24, ATM |
| HMGB1 Signaling | 3.0E-02 |
AKT1, RHOB, TNFRSF1A, RHOC,
MAP2K3 IL1R1, ATM |
| Huntington’s Disease Signaling | 5.8E-03 |
HDAC9, HSPA1A/HSPA1B, DNM3,
HSPA5 HSPA1L, ZDHHC17, HSPA8, TGM2, DYNC1I2 AKT1, CREB1, GNB2, GNG5, PRKD1, ATM |
| Hypoxia Signaling in the Cardiovascular System |
1.9E-02 |
AKT1, EDN1, UBE2G1, CREB1,
HSP90AA1 ATM |
| IL-1 Signaling | 3.0E-02 |
TRAF6, MAP3K1, GNB2, GNAI1,
GNG5 MAP2K3, IL1R1 |
| IL-10 Signaling | 2.2E-02 | TRAF6, SOCS3, IL4R, IL1RL1, MAP2K3, IL1R1 |
| IL-6 Signaling | 1.3E-02 |
TRAF6, SOCS3, AKT1, TNFRSF1A,
IL1RL1 HSPB7, MAP2K3, IL1R1, ATM |
| IL-8 Signaling | 3.0E-03 |
NAPEPLD, RHOC, GNAI1, CCND1,
PLD1 TRAF6, CDH1, AKT1, CCND3, RHOB, GNB2 GNG5, PRKD1, ATM |
| LPS/IL-1 Mediated Inhibition of RXR Function |
2.7E-02 |
ALDH4A1, TNFRSF1A, IL1RL1,
MAP3K1 IL1R1, FMO5, TRAF6, ALDH1L1, UST, ACSL5 NR5A2, SLC27A3, HS3ST5 |
| LXR/RXR Activation | 4.2E-02 |
SCD, TF, TNFRSF1A, IL1RL1, MYLIP,
ACACA S100A8, IL1R1 |
| Melanoma Signaling | 4.5E-02 | CDH1, AKT1, CCND1, ATM |
| P2Y Purigenic Receptor Signaling Pathway |
6.0E-03 |
PLCD1, AKT1, CREB1, GNB2, GNAI1,
P2RY12 GNG5, PLCD4, PRKD1, ATM |
| p38 MAPK Signaling | 3.6E-02 |
TRAF6, TNFRSF1A, IL1RL1, DUSP10,
CREB1 HSPB7, MAP2K3, IL1R1 |
| Phospholipase C Signaling | 4.0E-02 |
HDAC9, NAPEPLD, RHOC, ARHGEF17,
PLD1 TGM2, RHOB, CREB1, GNB2, GNG5 ARHGEF2, MYL3, PRKD1 |
| Phospholipases | 3.5E-02 | PLCD1, NAPEPLD, PLA1A, PLCD4, PLD1 |
| Protein Kinase A Signaling | 3.9E-02 |
TCF4, PXN, PTPRD, MAP3K1, GNAI1,
TTN PDE8A, PLCD1, DUSP10, CREB1, GNB2 GNG5, DUSP7, PLCD4, MYL3, PDE6B TCF7L2, PRKD1, DUSP16 |
| Role of BRCA1 in DNA Damage Response |
4.4E-02 | MSH2, GADD45A, BLM, FANCL, ATM |
| Role of NFAT in
Cardiac Hypertrophy |
3.3E-02 |
PLCD1, HDAC9, AKT1, MAP3K1,
GNB2 GNAI1, GNG5, MAP2K3, PLCD4, PRKD1, ATM |
| Role of PKR in Interferon Induction and Antiviral Response |
3.9E-02 | TRAF6, AKT1, TNFRSF1A, MAP2K3 |
| Superpathway of D-myo-inositol
(1,4,5)-trisphosphate Metabolism |
4.1E-02 | INPP1, ITPKC, IMPA2 |
| Thrombin Signaling | 8.9E-03 |
RHOC, GNAI1, PLCD1, AKT1, RHOB,
CREB1 GNB2, GNG5, ARHGEF2, PLCD4, MYL3 PRKD1, ATM |
| Thyroid Cancer Signaling | 3.9E-02 | CDH1, TCF4, CCND1, TCF7L2 |
| Xanthine and Xanthosine Salvage |
3.2E-02 | PNP |
| γ-linolenate Biosynthesis
II (Animals) |
1.6E-02 | ACSL5, CYB5R3, SLC27A3 |