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Table 10 Summary of IPA analyses of RNAs obtained from δ-tocotrienol treatment of hepatitis C patients

From: δ-Tocotrienol feeding modulates gene expression of EIF2, mTOR, protein ubiquitination through multiple-signaling pathways in chronic hepatitis C patients

#

Subjects

P-Value ovrlap

Overlap

#

Subjects

P-Value ovrlap

# Molecules

I

Top Canonical Pathways

  

VII

Cardiotoxicity

  

1

EIF2 Signaling

1.28E-37

30.3 % 67/221

31

Cardiac Infarction

3.62E-01 - 5.40E-04

23

2

Regulation of eIF4 and p70S6K Signaling

5.38 E-140

21.0 % 33/157

32

Caediac Necrosis/Cell Death

1.65E-01 - 2.56E-03

23

3

mTOR Signaling

1.28 E-13

18.4 % 37/102

33

Cardiac Dycfunction

4.31E-01 - 2.63E-03

11

4

B Cell Receptor Signaling

8.35 E-08

14.2 % 27/190

34

Cardiac Fibrosis

1.77E-01 - 5.68E-03

14

5

Signaling

1.72E-06

16.2 % 18/111

35

Cardiac Transformation

1.10E-02 - 1.10E-02

2

II

Top Upstream Regulators

 

Predicted Activation

VIII

Hepatotoxicity

  

6

ST 1926

5.62E-20

Activated

36

Liver Proliferation

2.15E-01 - 5.85E-05

26

7

Sirolimus

2.32E-18

Activated

37

Liver Necrosis/Cell Death

6.13E-01 - 6.59E-05

29

8

CD 437

1.45E-17

Activated

38

Liver Damage

4.69E-01 - 1.81E-04

35

9

RICTOR

1.64E-17

Activated

39

Liver Inflamma/Hepatitistion

4.52E-01 - 5.02E-04

36

10

MYCN

3.22E-15

Inhibited

40

Liver Cirrhosis

4.19E-02 - 1.65E-03

21

III

Diseases and Disorder

 

# Molecules

IX

Nephrotoxicity

  

11

Infectious Diseases

1.14E-04 - 1.29E-24

244

41

Renal Necrosis/Cell Death

3.32E-01 - 7.15E-05

46

12

Immunological Disease

7.41E-05 - 2.37E-23

372

42

Renal Inflammation

3.74E-01 - 1.69E-03

33

13

Cancer

1.25E-04 - 4.75E-22

839

43

Renal Nephritis

3.70E-01 - 1.69E-03

33

14

Organismal Injury and Abnormalities

1.36E-04 - 4.75E-21

865

44

Renal Damage

5.15E01 - 3.12E-03

21

15

Tumor Morphology

1.19E-04 - 4.75E-21

82

45

Glomerular Injury

1.00E-00 - 1.47E-02

22

IV

Molecular and Cellular Functions

 

# Molecules

X

Top Regulator Effect Networks

Disease & Functions

Consistency Score

16

Cellular Development

1.24E-04 - 1.29E-24

222

46

Ap1,CAMP,F2RL1,IL17A,IL1RN,KITLG,mir10,NRG1,SELP (+2 >)

Activationof antigen presenting cells (+11 >)

40.848

17

Cellular Growth and Proliferation

1.24E-04 - 1.29E-24

206

47

AP1,CAMP,EIF2AK2,F2RL1,IL17A,IL1RN, KITLG (+2 >)

Activationof phagocytes (+9 >)

36.338

18

Cell Death and Survival

1.36E -04 - 3.94E-21

371

48

26s Proteasome,ANGPT2,AP1,BCL2,CAMP,CEBPA,F2RL (+6 >)

Activationof antigen presenting cells (+10 >)

32.199

19

Cell-To-Cell Signalingand Interaction

1.34EE-18-04 - 7.04

183

49

26s Proteasome,CAMP,CSF1,IL17A,JUN,LDL (+5 >)F2RL (+6 >)

Activationof antigen presenting cells (+7 >)

30.414

20

Cellular Function and Maintenance

1.02E-04 - 2.10E-16

232

50

AP1,CAMP,CCL5,EIF2AK2,F2RL1,FGF10,IL17A,IL1RN (+5 >)

Accumulation of leukocytes (+19 >)

30.375

V

Physiological System Development and Function

 

# Molecules

XI

Top Networks (Associated Network Functions)

 

Score

21

Hematological System Development and Function

1.34E-04 -1.29E-24

255

51

Developmentall Disorder, Hereditary Disorder, Metabolic Diseases

46

22

Lymphoid Tissue Structure and Development

1.33E-04 -1.29E-24

194

52

Cancer, Cell Death and Survival, Organismal Injury and Abnormalities

44

23

Tissue Morphology

1.19E-04 - 2.45E-19

184

53

Post-Translational Midification, Cell Cycle, Cellular Development

44

24

Immune Cell Trafficking

1.34E-04 - 7.04E-18

160

54

Cancer, Hematological Disease, Immunological Disease

 

41

25

Hematopoiesis

1.02E004 - 6.87E-14

130

55

Protein Synthesis, RNA Post-Transcriptional Modification, Gene Expression

39

VI

Top Tox Functions (Clinical Chemistry and Hematology)

 

# Molecules

XII

Top Toxicology Lists

p-value

Overlap

26

Increased Levels of Albumin

2.38E-01 - 1.24E-02

4

56

Renal Necrosis/Cell Death

1.58E-05

8.60 % 46/538

27

Increased Levels of Alkaline Phosphatase

2.12E-01 - 4,42E-02

6

57

Liver Prolification

1.80E-05

11.0 % 26/236

28

Decreased Levels of Hematocrit

5.71E-02 - 5.71E-02

2

58

Liver Necrosis/ Cell Death

8.35E-05

9.6 % 29/303

29

Increased Levels of Hematocrit

6.20E-02 - 6,20E-02

8

59

Mechanism of Gene regulation by Peroxisome

2.74E-04

13.7 % 13/95

30

Increased Levels of Potassium

5.36E-01 - 8.64E-02

2

60

Increases Liver Damage

7.40E-04

11.4 % 15/132

A

Gene Expression Fold Change (Up-regulated)

Expression Value

 

B

Gene Expression Fold Change (Down-regulated)

Expression Value

 

1

SNORD15A

581.151

 

1

HMGN1P3

-381.06

 

2

SNORA32

390.353

 

2

SNHG25

-350.0555

 

3

SNORA56

185.194

 

3

SNORA67

-148.69

 

4

SNORA9

124.698

 

4

RPL17-C18orf32

-67.253

 

5

SNORS3B

102.91

 

5

ISY1-RAB43

-51.147

 

6

SNORA3A

93.09

 

6

ARHGEF18

-41.381

 

7

HIST1H2AD

20.784

 

7

KLRC4-KLRK1/KLK1

-20.578

 

8

SNORD3D

17.157

 

8

HIST1H3J

-19.795

 

9

LINC00305

4.853

 

9

MTHFS

-18.71

 

10

HHIPL2

4.844

 

10

SNORA16A

-18.285