Table 2. Selected canonical signaling pathways affected at 7 days and 6 months after LVAD implant.
| Ingenuity Canonical Pathways |
7 days post LVAD
|
6 months post LVAD
|
Comparison | ||
|---|---|---|---|---|---|
| p | Genes | p | Genes | Genes that change direction | |
| Interferon Signaling | 0.0010 | IFIT3, IFIT1, RELA, JAK1, IFI35, STAT1, IFNAR1, IRF1 | 0.0500 | BAX, IFNAR1, PSMB8, TYK2 | |
| Activation of IRF by Cytosolic Pattern Recognition Receptors | 0.0135 | IFIH1, RELA, RIPK1, LTA, DDX58, SIKE1, STAT1, IFIT2, IFNAR1 | 0.0363 | MAP2K4, TRAF3, PPIB, MAPK9, IKBKE, IRF3, ATF2, TANK, IRF7, IKBKG, RIPK1, IKBKAP, PIN1, NFKBIB, TNF, IFNAR1 | RIPK1 |
| CTLA4 Signaling in Cytotoxic T Lymphocytes | 0.0001 | CD247, AP2B1, HLA-DOA, PPP2R5D, CD4, AP1S2, PPP2R5B, HLA-DQA1, HLA-DRB1, AP2S1, PPP2CB, PIK3C3, HLA-DRA, CLTCL1, PIK3R6, PPP2R5C | 0.0010 | FYN, CD3E, PIK3R1, CD4, CLTB, PIK3R5, TRAT1, HLA-DRB1, PPP2R3B, LCK, PIK3C3, PIK3CG, HLA-DRA, ATM, AKT2, PTPN6, AP1M1, CLTC, CD3D, PPP2R1A, PTPN11, CLTA, PPP2R2B, ZAP70, FCER1G, AP1G1, LCP2 | HLA-DRB1, HLA-DRA |
| NF-KB Activation by Viruses | 0.0389 | RAF1, RELA, CCR5, RIPK1, CD4, PIK3C3, PIK3R6, ITGAV, ITGAL | 0.0015 | SIGIRR, AZI2, TRAF3, TGFBR1, PIK3R1, UBE2N, TLR8, PIK3R5, TNFAIP3, HRAS, KRAS, TANK, TGFBR2, IKBKG, LCK, TLR10, MAP3K7, PIK3C3, PIK3CG, CSNK2A1, TDP2, NFKBIB, CASP8, ATM, MAP3K14, AKT2, RRAS, RELB, MALT1, TAB 3, TLR2, TLR4, RIPK1, BCL10, ZAP70, FCER1G, MAP3K8, TIRAP, TNF, MAP3K3, CARD11, IRAK4, PRKCB | RIPK1, PIK3C3 |
| Antigen Presentation Pathway | 0.0003 | HLA-DOA, PDIA3, HLA-DRB3, HLA-DRA, HLA-DQA1, HLA-DRB1, CD74, HLA-DPB1, HLA-DPA1 | 0.0102 | HLA-DRB4, HLA-A, PDIA3, HLA-DRB3, HLA-DRA, HLA-B, HLA-DRB1, PSMB8, CD74, HLA-F, HLA-DPB1, PSMB6 | HLA-DRB3, HLA-DRA, HLA-DRB1, CD74, HLA-DPB1 |
| OX40 Signaling Pathway/T-Cell Survival | 0.0009 | CD247, BCL2L1, RELA, HLA-DOA, CD4, HLA-DRB3, HLA-DRA, HLA-DQA1, HLA-DRB1, HLA-DPB1, HLA-DPA1 | 0.0045 | MAP2K4, TNFSF4, TRAF3 , TNFRSF4, CD3E, HLA-A, CD4, HLA-DRB1, MAPK9 , CD3D, HLA-DRB4, HLA-DRB3, HLA-DRA, HLA-B, FCER1G, HLA-F, NFKBIB, HLA-DPB1 | CD4, HLA-DRB3, HLA- DRB1, HLA-DPB1 |
| T Helper Cell Differentiation | 0.0263 | STAT4, CD40LG, HLA-DOA, HLA-DRA, HLA-DQA1, HLA-DRB1, STAT1, TBX21, GATA3 | 0.1432 | IL6ST, IL2RG, TGFBR1, IL12RB1, IL6R, HLA-DRB1, STAT3, TBX21, TGFBR2, ICOS, TGFB1, HLA-DRA, FCER1G, IL2RA, TNF | TBX21 HLA-DRA |
| Ingenuity Canonical Pathways | 7 days post LVAD | 6 months post LVAD | Comparison | ||
| p | Genes | p | Genes | Genes that change direction | |
| Allograft Rejection Signaling | 0.0062 | PRF1, CD40LG, HLA-DOA, HLA-DRB3, HLA-DRA, HLA-DQA1, HLA-DRB1, HLA-DPB1, HLA-DPA1 | 0.0525 | HLA-A,HLA-DRB1, IGHG1, PRF1, IGHG3, HLA-DRB4, HLA-DRB3, HLA-DRA, FCER1G, HLA-B, IGHG4, HLA-F, HLA-DPB1, TNF , GZMB | PRF1, HLA-DRB3, HLA-DRA, HLA-DRB1 HLA-DPB1 |
| Glutathione Redox Reactions I or II | 0.0093 | MGST1, GPX1, GPX4, PRDX6 | 0.0275 | GSR, GLRX | |
| IL-15 Signaling | 0.0135 | BCL2L1, RAF1, RELA, STAT5A, JAK1, PIK3C3, PIK3R6, MAPK13, IL2RB | 0.0178 | RAF1, IL2RG, AKT2, RRAS, PIK3R1, TYK2, PIK3R5, HRAS, KRAS, STAT3, RAC3, LCK, MAPK14, PIK3C3, PIK3CG, STAT5B, ATM | RAF1 |
| 14-3-3-mediated Signaling | 0.0224 | RAF1 , YWHAG, PDIA3, YWHAB, TUBB2A , MAP3K5, TUBB, TUBA1B, YWHAQ, PIK3C3, PIK3R6, SNCA, AKT1S1 | 0.0008 | MAP2K4, TSC1, RAF1, BAD, PDIA3, PIK3R1, PIK3R5, HRAS, KRAS, MAP3K5, PLCH2, TUBB4A , PIK3CG, PIK3C3, PLCL1, PDCD6IP, PLCD4, ATM, TUBB1 , AKT2, RRAS, TUBB4B, TUBG1 , MAPK9, VIM, BAX, PLCL2, CBL, TUBA3C/TUBA3D, CDKN1B, TNF, PRKCB | RAF1 |
| Cytotoxic T Lymphocyte-mediated Apoptosis of Target Cells | 0.0054 | CD247, PRF1, HLA-DOA, HLA-DRB3, HLA-DRA, HLA-DQA1, HLA-DRB1, HLA-DPB1, HLA-DPA1 | 0.0039 | CASP3 , CD3E, CYCS, HLA-A, APAF1 , HLA-DRB1, CD3D, PRF1, HLA-DRB4, HLA-DRB3, HLA-DRA, FCER1G, HLA-B, CASP8 , HLA-F, HLA-DPB1, GZMB | HLA-DRB3, HLA-DRA, HLA-DRB1, HLA-DPB1 |
| RAN Signaling | 0.0003 | KPNB1, KPNA3, CSE1L, RANBP2, RAN, IPO5 | 0.0363 | KPNA3, KPNA4, CSE1L, RANGAP1, RAN, RANBP1 | CSE1L |
| VEGF Signaling | 0.0437 | EIF1AY, VEGFA, BCL2L1, RAF1, PIK3C3, PIK3R6, VEGFB, EIF2B3, ELAVL1, PGF | 0.0045 | MAP2K4, TNFSF4, TRAF3 , TNFRSF4, CD3E, HLA-A, CD4, HLA-DRB1, MAPK9 , CD3D, HLA-DRB4, HLA-DRB3, HLA-DRA, HLA-B, FCER1G, HLA-F, NFKBIB, HLA-DPB1 | |
| Cardiac Hypertrophy Signaling | - | - | 0.0035 | MAP2K4, RAF1, TGFBR1, MAP3K11 , PIK3R1, HRAS , KRAS, PLCH2 , TGFBR2, MAP3K10 , GNB4, RHOG, GNA15, TGFB1 , PIK3CG, GNA13, PLCL1, ATM, MAP3K2, MAP3K14, RRAS , IL6R, PLCL2, CACNA1A , ATF2, MYL12A , RHOQ, EIF2B5, FNBP1, EIF2B4, PDIA3, RHOT2 , PIK3R5, MAP3K5, EIF2B2 , MTOR, MAP3K7, PIK3C3 , SOS1, PLCD4, MAP3K6 , MAPKAPK3, MEF2A, GNAQ, MAPK9, ROCK1, MAPK14, PRKAR2B, MAP3K8, MAP3K3, ADCY7, PRKAR1A | |
Differentially expressed transcripts with an FDR <0.10 at each time point were analyzed with Ingenuity Pathways Analysis (IPA). The fraction of genes in the dataset involved in known signaling pathways is determined and a p-value is calculated to estimate the likelihood the finding is due to chance alone. The transcripts within each pathway are shown with Bold = down, italic = up.