Combine Genetic, Molecular, Cellular and Statistical Analysis to

Determine Disease Variations

Bingjie Li

The University of Texas Health Science Center at Houston, TX 77030, USA

Background

• Precision medicine will improve patient managements and emphasize the differences from both host and pathogens for every disease.

• Statistics helps to identify those differences and advance the clinical acknowledgement.

Identify A Single Host Gene Mutation Changes Disease Onset, Severity,

Location and Molecular Abnormalities

• Fas gene mutation (Faslpr and Fas+)

• Systemic lupus erythematosus (SLE)

• Organ: lung, kidney, liver, and joints

• Molecular marker: MMP, IL-11 and CXCR4

C3

(m

g/m

l)

n=3 3 3 3

Faslpr Faslpr Fas+ Fas+ Model

P=0.4984 P=0.1133

Overall P=0.0031

Faslpr P=0.0136 Fas+ P=0.0218

Time (month) 2 4 A Complement Component 3

Uri

ne

Cre

atin

ine

(m

g/d

l)

Time (month) 2 4 C Urine Albumin

P=0.3940 P=0.0153

Overall P=0.0026

n=3 4 4 3

Faslpr Faslpr Fas+ Fas+ Model

Time (month) 2 4 D ACR

P=0.8954 P=0.0135

Time (month) 2 4 B Urine Creatinine

P=0.5299 P=0.2334

Overall P<0.0001

Overall P=0.0036

Faslpr P=0.0001

Faslpr P=0.0395 Faslpr P=0.0279

Fas+ P=0.0043

Fas+ P=0.0307

Fas+ P=0.0309

n=3 4 4 3

Faslpr Faslpr Fas+ Fas+ Model

n=3 4 4 3

Faslpr Faslpr Fas+ Fas+ Model

Alb

um

in (m

g/d

l)

Alb

um

in c

reat

inin

e r

atio

Control Fas+

A C B F D E

Color MMP MMP/X-ray X-ray Color/MMP/X-ray Color/MMP

G I H L J K

Color MMP MMP/X-ray X-ray Color/MMP/X-ray

Faslpr Fas+

Fas+ Faslpr Kid

ne

y-to

-mu

scle

rat

io

P<0.0001

N=4 4

Statistical Analysis Heart/Lung

Liver Spleen

Kidney

Muscle Bone Knee

Blo

od

A

Fas+ Faslpr IL-11

Fas+ Faslpr

P=0.0002

E IL-11 Lung

Lun

g-to

-mu

scle

rat

io

N=5 5

Fas+ Faslpr

P=0.0139

N=5 5

B

Kn

ee

-to

-mu

scle

rat

io

F IL-11 Knee

C

G

Fas+ Faslpr CXCR4

Fas+ Faslpr

P<0.0001

CXCR4 Liver

Live

r-to

-mu

scle

rat

io

N=5 5

IL-11

Fas+

Faslpr

H Kidney weight

D

Kid

ney

we

igh

t (g

)

P<0.0001

Fas+ Faslpr

N=10 8

Fas+ Faslpr

12

.38

12

.23

9.9

7

5.45

10

.12

5.31 7.87 6.67

Kidney size (mm)

MM

P-2

(n

g/m

l)

n=3

Model

Time (month)

A Serum MMP-2

Overall P=0.0072

2 4 3 2 4 3

B Serum MMP-9

Overall P<0.0001

MM

P-9

(n

g/m

l)

Faslpr Fas+

P=0.0274 P=0.0252

P=0.0002

P=0.0488 P=0.0075

P=0.0133

P=0.0123

P=0.0159

P=0.0103

P=0.0119

P=0.0134

Identify Molecular Difference of Pathogen

• Clostridium Difficile (C. Difficile)

• Pseudomembranous colitis

• Disease Rate:

• Initial recurrence rate: 25%

• Secondary recurrence rate: 45%

• Third recurrence rate: 65%

Floor Source 21 1

21 2

21 3

15 4

7 5

21 6

21 7

21 8

21 9

21 10

21 11

21 12

21 13

21 14

21 15

21 16

15 17

7 18

7 19

21 20

15 21

15 22

15 23

15 24

7 25

7 26

7 27

7 28

7 29

7 30

21 31

15 32

15 33

7 34

7 35

7 36

7 37

7 38

7 39

21 40

21 41

21 42

21 43

21 44

21 45

15 46

15 47

15 48

21 49

21 50

7 51

7 52

7 53

7 54

7 55

7 56

15 58

7 60

21 65

21 72

7 68

7 69

7 92

7 93

21 101

21 96

21 97

7 84

21 77

7 70

21 71

21 103

7 82

7 91

21 88

7 106

7 107

7 78

7 80

7 86

15 89

7 109

21 99

21 102

7 108

7 111

7 61

7 67

7 112

7 113

7 104

7 110

21 98

15 57

7 62

7 59

21 100

7 73

21 76

7 63

7 105

7 64

7 94

7 74

21 66

7 83

7 87

7 81

7 85

15 90

7 75

7 79

21 95

7 115

21 116

7 127

21 123

21 124

21 125

21 117

21 118

15 119

21 121

15 120

21 122

21 126

7 128

7 129

7 130

7 131

15 132

15 133

15 134

15 135

15 136

7 137

7 138

7 139

21 140

21 141

21 142

21 144

21 143

21 145

15 146

15 147

15 148

15 149

15 150

15 151

15 152

7 153

7 154

7 155

7 156

21 157

15 158

15 159

15 160

15 161

15 162

15 163

15 164

7 165

7 168

7 169

7 170

21 171

21 172

15 173

15 175

15 177

15 179

15 178

15 181

15 182

15 180

15 183

Floor A/ Floor B/ Floor C/Environment (living & bath room)/Patient (stool)

P Value

0.2236

Floor (Positive/Total)

3 (6/67=9%)

1 (1/39=3%)

2 (1/47=2%)

0.8475

3 (5/67=75%)

1 (2/39=5%)

2 (4/47=9%)

0.3136

3 (1/67=1%)

1 (3/39=8%)

2 (2/47=4%)

Conclusion

• Biostatistics helps identifying the differences from both host and pathogen sides.

• The genetic differences of the host and pathogen could be the contributors that cause treatment failure.

• The combination of genetic, molecular, cellular and statistical analysis will help us to understand the diseases and develop precision medicine.

Acknowledgement

Shoufan Hu, Shi Ke, Hua Chen, Zhi-Dong Jiang, Herbert L. DuPont.

Reference

S. Hu, S. Ke, W. Wang, H. Ran, M. Chen, F. Zhang, X. Qiu, M. Jiang, C. Zou. R. Zhang, L. Cao, Y. Wen, R. Fu and C. Chen. A Single Fas Gene Mutation Changes Lupus Onset, Severity, Location, and Molecular Abnormalities in Mice. Current Molecular Medicine; 2015: (15) 1-6.

Thank you!