Table 4. Upstream regulators predicted to be activated or inhibited in the proteomic dataset.
| Upstream Regulator2 | Predicted Activity (In HFE) | Activation z-score | p-value of overlap |
Target molecules used in predictions: No underline: up-regulated in low FE Underline: up-regulated in high FE (Names of proteins corresponding to abbreviations can be obtained from Tables 1 & 2) |
|---|---|---|---|---|
| INSR | Activated | 2.425 | 4.29E-05 | ACTA1, GAPDH, TP5O, COX4I1, FABP4, MYOM2, NDUFV2, OGDH, UQCRC1, UQCRC2 |
| NFE2L2 | Activated | 2.382 | 1.54E-06 | ACTG1, SOD1, RF1, EIF4G2, GNB2L1, GPX1, IDE, NARS, PPIB, PSMA5, PSMB1, PSMD1, RYR3, |
| IGF1R | Activated | 2.236 | 2.95E-04 | ACTA1, ATP5O, COX4I1, MYOM2, NDUFV2, UQCRC1, UQCRC2 |
| progesterone | +++ | 1.954 | 4.55E-02 | ACTA1, CAV1, IDE, KRT15, RAP1B, RYR3, YWHAG |
| PRKAA2 | +++ | 1.951 | 3.20E-03 | ACTA1, ALB, P4HB,COX4I1, |
| T3 | +++ | 1.914 | 1.15E-03 | ACTA1, ACTC1, ALB, APOA1, COX4I1, CTH, FABP4, PRDX3 |
| PPARA | + | 1.571 | 1.18E-03 | ACTA1, ALDH9A1, APOA1, PBLD, COX4I1, CTH, FABP4, GLUD1, UQCRC1 |
| PPARGC1A | + | 1.531 | 4.37E-05 | ATP5O, COX4I1, FABP4, GPX1, NDUFV2, PRDX3, SOD1 |
| SRF | --- | -1.961 | 1.49E-03 | ACTA1, ACTC1, CKM, LBD3, MYL1, DMD, GLRX3 |
| MAP4K4 | Inhibited | -2.000 | 6.85E-03 | NDUFS8, OGDH, PFKM, UQCRC1 |
| RICTOR | Inhibited | -3.873 | 7.58E-11 | ATP5O, COX4I1, NDUFB8, NDUFS7, NDUFS8, NDUFV2, PPA2, PSMA5, PSMB, PSMD1, PSMD2, RPL12, RPL30, UQCRC1, UQCRC2 |
1 Prediction of activity of upstream regulators (positive or negative) based on activation z scores and p value of overlap (See Materials and Methods). Classification of activities are shown as predicted significantly strong positive or predicted strong negative based on a activation z score of > 2 and <−2, respectively. Qualified classifications of strong, moderate, or weak activation are indicated by +++, ++, +, respectively and qualified classification of strong inhibition is indicated by—.
2 Abbreviations: INSR, insulin receptor; IGF1R, insulin like growth receptor 1; NFE2L2, nuclear factor, erythroid 2-like 2; AMPKα, AMP activated protein kinase (α subunit), progesterone; T3, triiodothyronine; PPARA, peroxisome proliferator-activated receptor; PPARGC1A, peroxisome proliferator-activated receptor gamma coactivator 1-alpha; RICTOR, rapamycin independent companion of target of rapamycin; MAP4K4, mitogen-activated protein kinase kinase kinase kinase 4; SRF, serum response factor.