Table 1.
Upstream regulator analysis - using Ingenuity - of the mRNAs that were differentially expressed in GAS-treated mice compared to controls (WATER-GAS vs WATER-PBS) (1) and in GAS-treated mice neonatally exposed to CORT compared to GAS-treated mice (CORT-GAS vs water-GAS) (2).
| Upstream Regulator | WATER-GAS vs WATER-PBS (1) | CORT-GAS vs WATER-GAS (2) | Target genes |
|---|---|---|---|
| Chemicals - endogenous mammalian | |||
| beta-estradiol | −1,97 | 2,47 | (1): Btg2, Cbl, Cshl1, Enpp2, Fos, Inpp5j, Sdc3, Sema3b, Srd5a1, Tnnt3; (2): Adm, Bcat1, Bmp2, Calb1, Ccng1, Cdkn2b, Chgb, Ctps1, Dlg2, Fgf9, Fmo1, Fnbp1, Fzd2, Gab2, Gsk3b, Hsd17b12, Ier2, Insl3, Lhcgr, Lmcd1, Mapt, Mpz, Myh3, Nedd4l, Nkx2–1, Notch3, Pak5, Pdap1, Pitpna, Ptgds, Pttg1, Pxdn, Pycr1, Pygl, Qsox1, Rapgef6, Slc38a2, Smad3, Snap25, Sstr4, Tgfb3, Thrsp, Timp3, Tpo, Trib1, Vav3, Zyx |
| butyric acid | — | 2,16 | Calb1, Ccng1, Col5a2, Gli3, Ly6e, Myh3, Nfatc4, Oas2, Ptgds, Pygl, Serpine1, Timp3, Uqcrq |
| dihydrotestosterone | −1,95 | — | Btg2, Elovl7, Fos, Sdc3, Slc7a7, Srd5a1 |
| dopamine | — | 1,63 | Adra2c, Bcl2l2, Gprc5b, Ncf1, Ppp2r2a, Scn1b, Scn9a |
| L-dopa | — | −4,59 | Adra2c, Ajap1, C1qtnf12, C2cd2l, Cbr3, Cdc42ep2, Csmd3, Cyld, Dgki, Dlg2, Grid2, Kcne5, Klf16, Mpp6, Nedd4l, Per2, Plekha2, Ppp2r2a, Ptprd, Rell1, Reln, Slc38a2, Sorcs2, Wdr17, Zfhx3 |
| oleic acid | — | −2,00 | Ncf1, Npc1l1, Serpine1, Thrsp |
| Complexes | |||
| IgG | — | −2,24 | Adm, Cdkn2b, Csnk2b, Ier2, Serpine1 |
| LH | — | 2,00 | Actn1, Btc, Gprc5b, Insl3, Lhcgr, Snap25, Thbs2, Trib1 |
| IL-2 | — | −1,76 | Bmp2, Card9, Ccng1, Ccr6, Cmklr1, Csf2rb, Csrnp1, Ctps1, Dapk2, Gcnt1, Ly6e, Pus1, Tnfrsf4 |
| Enzymes | |||
| CASZ1 | — | −1,96 | Acan, Myh3, Nefl, Tgfb3 |
| EGLN1 | — | −1,98 | Acan, Adm, Cdkn2b, Tgfb3 |
| TGM2 | — | 1,91 | Acan, Csrnp1, Dapk2, Ifit2, Ly6e, Mpp6, Oas2 |
| Growth Factors | |||
| FGF2 | −1,93 | — | Btg2, Enpp2, Fos, Prkce, Ptma (Includes Others) |
| INHBA | — | −2,34 | Actn1, Bmp2, Calb1, Cdkn2b, Edar, Lhcgr, Nkx2–1, Pcdh9, Serpine1, Vav3 |
| LEP | — | −2,16 | Cps1, Dffa, Gsk3b, Insl3, Ncf1, Per2, Pln, Rfx1, Serpine1, Snap25, Thrsp, Timp3 |
| Kinases | |||
| IKBKB | — | −1,98 | Bmp2, Cdh13, Timp3, Tnfrsf4 |
| Transcription Regulators | |||
| KMT2A | — | 2,00 | Gcnt4, Pigz, Trib1, Zmat4 |
| NKX2–3 | — | −1,61 | Adm, Bmp2, Cd34, Cerk, Cryab, Csrnp1, Ly6e, Srpx2, Tmem158 |
| TP53 | — | 2,11 | Actn1, Apbb2, Ccng1, Col5a2, Col9a1, Cryab, Csmd3, Fmo1, Gsk3b, Hs3st1, Kcng1, Kifc1, Me2, Nab1, Ncf1, Otx1, P2rx4, Ptgds, Ptger1, Pttg1, Serpine1, Sirt6, Tgfb3, Thbs2, Timp3, Tmem151a, Zyx |
| TP63 | — | −1,78 | Adm, Bmp7, Ccng1, Cdkn2b, Kcng1, Notch3, Serpine1, Smad3, Smad4, Tgfb3, Timp3 |
| Transmembrane Receptors | |||
| TREM1 | — | −2,45 | Cdkn2b, Ifit2, Nedd4l, Nme7, Rhou, Tmem158 |
All upstream regulators are listed with a z-score ≤ −1,50 or ≥1,50 or (see Supplementary Methods), indicating that they are inhibited or activated, respectively. The upstream regulators that could be linked to streptococcal/GAS infection, CORT exposure and/or OCD/tic disorders are indicated in bold. For each regulator, the downstream target genes are listed.