1 Legend to supplemental Figure 1 MMP-9 and MMP-2 activity in plasma from HD, BPH and PCa patients. Panel A. Zymograms showing gelatinolytic activity in representative plasma. Note the increased intensity of the MMP-9 but not the MMP-2 lower band representative of the active enzyme. Samples were loaded onto 8% polyacrylamide gels co-polymerized with 1 mg/ml gelatin. After electrophoresis, gels were washed three times in 2.5% Triton X-100 at room temperature and incubated overnight at 37° C in 50 mM Tris– HCl, pH 7.5, 200 mM NaCl, 5 mM CaCl 2 and 0.02% Brij-35. Gels were stained with 0.5% Coomassie blue (w/v) in 25% methanol (v/v) and 10% acetic acid (v/v), and de-stained in the same solution without Coomassie blue. The supernatant of WM983A melanoma cells, activated or not with p-aminophenylmercuric acetate, was used as a reference standard for human pro-MMP-9, pro-MMP-2 and their activated forms. Plasma samples from HD were used as an internal standard. Panel B. MMP-9 activity quantified by densitometry and expressed as arbitrary units. Box plot shows median and 25 th and 75 th percentiles (whiskers = minimum and maximum values).
Transcript
1
Legend to supplemental Figure 1
MMP-9 and MMP-2 activity in plasma from HD, BPH and PCa patients.
Panel A. Zymograms showing gelatinolytic activity in representative plasma. Note the
increased intensity of the MMP-9 but not the MMP-2 lower band representative of the
active enzyme. Samples were loaded onto 8% polyacrylamide gels co-polymerized with 1
mg/ml gelatin. After electrophoresis, gels were washed three times in 2.5% Triton X-100
at room temperature and incubated overnight at 37° C in 50 mM Tris– HCl, pH 7.5, 200
mM NaCl, 5 mM CaCl2 and 0.02% Brij-35. Gels were stained with 0.5% Coomassie
blue (w/v) in 25% methanol (v/v) and 10% acetic acid (v/v), and de-stained in the same
solution without Coomassie blue. The supernatant of WM983A melanoma cells,
activated or not with p-aminophenylmercuric acetate, was used as a reference standard
for human pro-MMP-9, pro-MMP-2 and their activated forms. Plasma samples from HD
were used as an internal standard.
Panel B. MMP-9 activity quantified by densitometry and expressed as arbitrary units.
Box plot shows median and 25th
and 75th
percentiles (whiskers = minimum and maximum
values).
2
HD BPH CaP0
2
4
6
8
1010
20
30
P<0.001
MM
P-9
acti
vit
y(a
rbitra
ry u
nits)
P<0.001
P>0.05
B
BPH
PCa
PCa
PCa
PCa
HD
BPH
BPH
Pro-MMP-9►MMP-9►
Pro-MMP-2 ►
MMP-2 ►
A
HD BPH CaP0
2
4
6
8
1010
20
30
P<0.001
MM
P-9
acti
vit
y(a
rbitra
ry u
nits)
P<0.001
P>0.05
B
BPH
PCa
PCa
PCa
PCa
HD
BPH
BPH
Pro-MMP-9►MMP-9►
Pro-MMP-2 ►
MMP-2 ►
BPH
PCa
PCa
PCa
PCa
HD
BPH
BPH
Pro-MMP-9►MMP-9►
Pro-MMP-2 ►
MMP-2 ►
A
Supplemental Figure 1
HD BPH PCa
Su
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lem
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tary
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10
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12
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FA
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6
Bre
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Ca
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53
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1
Ca
lciu
m_
sig
na
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ath
wa
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KE
GG
17
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7A
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Ms)_
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22
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58
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11
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13
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NA
2IF
NA
4
Co
mp
lem
en
t_a
nd
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de
s_
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GG
65
KA
2M
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B2
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C1
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10
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1
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Da
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Pa
thw
ay
10
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KR
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TM
AT
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BR
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1B
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2C
CN
HC
DK
7C
HE
K2
CIB
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IDE
AC
IDE
BC
KN
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RY
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DB
1D
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MC
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2E
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C3
ER
CC
4E
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EX
O1
FA
NC
GF
EN
1G
22
P1
GA
DD
45
AG
AD
D4
5G
GM
LG
TF
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1
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M_
extr
ace
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r1
56
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DIP
OQ
AG
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EL
XA
ME
LY
BC
AN
BG
NC
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CO
L1
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11
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1A
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12
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3A
1C
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14
A1
CO
L1
5A
1C
OL
16
A1
CO
L1
7A
1C
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18
A1
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9A
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1A
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1A
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20
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22
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24
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5A
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OL
27
A1
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L2
A1
CO
L3
A1
CO
L4
A1
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EC
M_
inh
ibito
rs&
oth
er_
en
zym
es
82
SA
GT
AP
PC
hG
nC
HP
FC
HS
T1
CH
ST
10
CH
ST
11
CH
ST
12
CH
ST
13
CH
ST
2C
HS
T3
CH
ST
4C
HS
T5
CH
ST
6C
HS
T7
CH
ST
8C
HS
T9
CH
SY
1C
SG
lcA
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SS
3G
AL
NA
CT
-H
AB
P2
HA
BP
4H
AS
1H
AS
2H
AS
3H
YA
L1
HY
AL
2H
YA
L3
HY
AL
4H
YA
LP
1
EC
M_
me
mb
ran
e_
ce
ll-ce
ll_a
dh
esio
n1
38
SA
LC
AM
CD
H1
CD
H1
0C
DH
11
CD
H1
2C
DH
13
CD
H1
5C
DH
16
CD
H1
7C
DH
18
CD
H1
9C
DH
2C
DH
20
CD
H2
2C
DH
23
CD
H2
4C
DH
26
CD
H3
CD
H4
CD
H5
CD
H6
CD
H7
CD
H8
CD
H9
CE
AC
AM
1C
EA
CA
M1
9CE
AC
AM
21C
EA
CA
M3
CE
AC
AM
4C
EA
CA
M5
CE
AC
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6
EC
M_
me
mb
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ce
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61
SA
DR
M1
CD
16
4C
D2
09
CD
30
0A
CD
36
CD
44
CD
47
CD
6C
D9
CIB
1C
IB2
CIB
3C
IB4
HM
MR
ITF
G1
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ITF
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ITG
A1
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GA
11
ITG
A2
ITG
A2
BIT
GA
3IT
GA
4IT
GA
5IT
GA
6IT
GA
7IT
GA
8IT
GA
9IT
GA
DIT
GA
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GA
L
EC
M_
pro
tea
se
s2
04
SA
CE
AC
E2
AD
AM
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DA
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2A
DA
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5A
DA
M1
7A
DA
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DA
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9A
DA
M2
AD
AM
20
AD
AM
21
AD
AM
22
AD
AM
23
AD
AM
24
AD
AM
25
AD
AM
26
AD
AM
28
AD
AM
29
AD
AM
30
AD
AM
32
AD
AM
33
AD
AM
3A
AD
AM
3B
AD
AM
4A
DA
M5
AD
AM
6A
DA
M7
AD
AM
8A
DA
M9
EC
M-r
ece
pto
r_in
tera
ctio
n_
KE
GG
85
KA
GR
INC
D3
6C
D4
4C
D4
7C
HA
DC
OL
11
A1
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L1
1A
2C
OL
1A
1C
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1A
2C
OL
2A
1C
OL
3A
1C
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4A
1C
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4A
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4A
4C
OL
4A
6C
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5A
1C
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5A
2C
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5A
3C
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6A
1C
OL
6A
2C
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6A
3D
AG
1F
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FN
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1F
ND
C3
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ND
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FN
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5G
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GP
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P6
GP
9
EG
F_
PD
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alin
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Pa
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ay
96
SA
CT
R2
AC
TR
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KT
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2A
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3A
RA
F1
AR
HA
AT
F1
AT
F2
BA
DB
CL
2B
RA
FC
AS
P3
CA
SP
9C
CN
D1
CH
UK
CO
L1
A1
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EB
1C
SN
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CS
NK
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DU
SP
1D
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EG
FE
GF
RE
GR
1E
IF4
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LK
1E
NP
P2
FN
1F
OS
FO
XO
3A
En
do
the
lial_
Ce
ll_B
iolo
gy
12
1S
AB
CF
1A
CE
AC
E2
AD
AM
17
AG
TA
GT
R1
AG
TR
2A
LO
X5
AN
GP
T1
AN
GP
T2
AN
GP
TL
3A
NX
A5
AZ
U1
BA
XB
CL
2B
CL
2A
1B
CL
2L
1B
CL
6B
LR
1C
3C
4A
CA
SP
1C
AS
P1
0C
AS
P3
CA
SP
6C
CL
2C
CL
20
CC
L5
CD
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CE
BP
BC
FL
AR
Fo
ca
l_a
dh
esio
n_
KE
GG
19
3K
AC
TB
AC
TC
1A
CT
G1
AC
TN
1A
CT
N2
AC
TN
3A
CT
N4
AK
T1
AK
T2
AK
T3
AR
HG
AP
5B
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BC
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1B
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AP
N2
CA
V1
CA
V2
CA
V3
CC
ND
1C
CN
D2
CC
ND
3C
DC
42
CH
AD
CO
L1
1A
1C
OL
11
A2
CO
L1
A1
CO
L1
A2
Fo
late
_b
iosyn
the
sis
_K
EG
G3
7K
AL
PI
AL
PL
AL
PP
AL
PP
L2
AS
CC
3A
SC
C3
L1
AT
P1
3A
2D
DX
18
DD
X2
3D
DX
41
DD
X4
7D
DX
50
DD
X5
2D
DX
54
DD
X5
6D
HF
RE
P4
00
ER
CC
2E
RC
C3
FB
XO
18
FP
GS
GC
H1
GG
HIF
IH1
LG
P2
MO
V1
0L
1N
UD
T5
NU
DT
8P
TS
QD
PR
RA
D5
4B
G_
Pro
tein
-Co
up
led
_R
ece
pto
r9
6S
AD
OR
A1
AD
OR
A2
AA
DO
RA
2B
AD
OR
A3
AG
TR
1A
GT
R2
AG
TR
L1
AV
PR
1A
AV
PR
1B
AV
PR
2B
DK
RB
1B
DK
RB
2C
3A
R1
CA
CN
A1
DC
AL
CR
LC
AS
RC
CK
AR
CC
KB
RC
EL
SR
1C
NR
1C
NR
2C
RH
R1
CR
HR
2E
BI2
ED
G1
ED
G2
ED
G3
ED
G4
ED
G6
ED
G7
ED
G8
G_
Pro
tein
-Co
up
led
_R
ece
pto
r_II
97
SA
DR
A1
AA
DR
A1
BA
DR
A2
AA
DR
A2
BA
DR
A2
CA
DR
B2
AD
RB
3A
RR
B2
BL
R1
CC
R1
CC
R2
CC
R3
CC
R4
CC
R5
CC
R6
CC
R7
CC
R8
CC
R9
CC
RL
1C
HR
M1
CH
RM
2C
HR
M3
CH
RM
4C
HR
M5
CM
KL
R1
CX
3C
R1
CX
CR
3C
XC
R4
CX
CR
6C
YS
LT
R1
DR
D1
Ga
p_
jun
ctio
n_
KE
GG
95
KA
DC
Y1
AD
CY
2A
DC
Y3
AD
CY
4A
DC
Y5
AD
CY
6A
DC
Y7
AD
CY
8A
DC
Y9
AD
RB
1C
DC
2C
SN
K1
A1
CS
NK
1A
1L
CS
NK
1D
CS
NK
1E
CS
NK
1G
2C
SN
K1
G3
CX
36
DR
D1
DR
D2
ED
G2
EG
FE
GF
RG
JA
1G
NA
I1G
NA
I2G
NA
I3G
NA
QG
NA
SG
RB
2G
RM
1
Ge
ne
s_
co
nstitu
tin
g_
the
_P
I3_
kin
ase
_p
red
icto
r1
32
Po
tti e
t a
l.A
KR
7A
3A
NK
RD
32
AT
AD
2B
AR
D1
BR
D2
C1
0o
rf1
17
C1
3o
rf8
C2
1o
rf4
5C
6o
rf1
50
CA
SP
8A
P2
CC
NE
1C
CN
E2
CD
C2
5A
CD
C4
5L
CD
C6
CD
C7
CD
CA
5C
DC
A7
CD
T1
CH
EK
1C
SE
1L
CS
PG
5D
CL
RE
1B
DD
X1
0D
IPA
DN
MT
1E
ED
EG
R1
EX
OS
C6
FE
N1
FIG
NL
1
Ge
no
me
_S
tab
ility
_D
NA
_R
ep
air
11
3S
AN
KR
D1
7A
PE
X1
AP
EX
2A
TM
AT
RA
TX
N3
BR
CA
1B
RC
A2
BR
IP1
CC
NH
CD
K7
CE
TN
2C
IB1
CK
N1
DD
B1
DD
B2
DK
C1
DM
C1
ER
CC
1E
RC
C2
ER
CC
3E
RC
C4
ER
CC
5E
RC
C6
EX
O1
FE
N1
FL
J1
08
58
G2
2P
1G
TF
2H
1G
TF
2H
2G
TF
2H
3
G-P
rote
in_
Co
up
led
_R
ece
pto
rs_
Sig
na
ling
99
SA
DR
B2
AG
TR
1A
GT
R2
AN
GP
TL
4A
RR
B1
AR
RB
2B
CL
2B
CL
2L
1C
AL
CR
CA
SR
CC
ND
1C
CN
E1
CC
NE
2C
DK
N1
BC
FL
AR
CM
KL
R1
CO
L1
A1
CS
F3
CT
GF
CY
P1
9D
RD
1D
RD
2D
RD
5D
US
P1
4E
DG
1E
DG
2E
DG
3E
DG
4E
DG
5E
DG
7E
GR
1
G-P
rote
ins_
&_
Sig
na
ling
_M
ole
cu
les
96
SA
DC
Y1
AD
CY
3A
DC
Y4
AD
CY
5A
DC
Y6
AD
CY
7A
DC
Y9
AK
T1
AR
HA
AR
HG
EF
1B
RA
FB
TK
CD
C4
2C
HU
KC
RE
B1
DT
RE
GF
RE
PA
CG
NA
12
GN
A1
3G
NA
15
GN
AI2
GN
AI3
GN
AL
GN
AO
1G
NA
S1
GN
AT
1G
NA
T2
GN
AZ
GN
B3
GN
B4
Gro
wth
_F
acto
r8
4S
AM
HA
RT
S-1
BD
NF
BM
P1
BM
P1
0B
MP
2B
MP
3B
MP
4B
MP
5B
MP
6B
MP
7B
MP
8B
CE
CR
1C
LC
CS
F1
CS
F2
CS
F3
CS
PG
5C
XC
L1
DK
K1
EC
GF
1E
RE
GF
GF
1F
GF
11
FG
F1
3F
GF
14
FG
F1
7F
GF
19
FG
F2
FG
F2
2F
GF
23
He
dg
eh
og
_sig
na
ling
_p
ath
wa
y_
KE
GG
55
KB
MP
2B
MP
4B
MP
5B
MP
6B
MP
7B
MP
8A
BT
RC
CS
NK
1A
1C
SN
K1
A1
LC
SN
K1
DC
SN
K1
EC
SN
K1
G2
CS
NK
1G
3D
HH
FB
XW
11
GA
S1
GL
I1G
LI2
GL
I3G
SK
3B
HH
IPIH
HL
RP
2P
RK
AC
AP
RK
AC
BP
RK
AC
GP
RK
XP
RK
YP
TC
H1
PT
CH
2R
AB
23
Hyp
oxia
_S
ign
alin
g_
Pa
thw
ay
48
SA
DD
1A
DM
AG
PA
T2
AG
TP
BP
1A
NG
PT
L4
AR
D1
AR
NT
2A
ZU
1B
AX
BC
L2
BH
LH
B2
BIR
C5
CA
1C
A1
2C
A9
CA
MK
2G
CA
SP
1C
AT
CD
C4
2C
HG
AC
OL
1A
1C
RE
BB
PC
ST
BC
TG
FC
YG
BD
AP
K3
DC
TN
2D
NA
JB
1D
R1
EC
E1
EE
F1
A1
IL1
8_
pa
thw
ay
6m
sig
db
IL1
8IL
12
BIL
2C
AS
P1
IFN
GIL
12
A
IL3
_P
ath
wa
y1
5m
sig
db
RA
F1
CS
F2
RB
ST
AT
5A
JA
K2
SO
S1
GR
B2
HR
AS
ST
AT
5B
IL3
MA
PK
3IL
3R
AP
TP
N6
MA
P2
K1
FO
SS
HC
1
IL6
PA
TH
WA
Y2
3m
sig
db
RA
F1
CE
BP
BP
TP
N1
1S
RF
JA
K2
SO
S1
GR
B2
HR
AS
JU
NM
AP
K3
JA
K1
IL6
ST
IL6
RJA
K3
CS
NK
2A
1M
AP
2K
1F
OS
SH
C1
IL6
EL
K1
ST
AT
3IL
6P
AT
HW
Ana
IL7
PA
TH
WA
Y1
8m
sig
db
EP
30
0S
TA
T5
AB
CL
2S
TA
T5
BL
CK
IL2
RG
JA
K1
JA
K3
PIK
3C
AP
IK3
R1
IL7
RP
TK
2B
IL7
NM
IF
YN
CR
EB
BP
IL7
PA
TH
WAn
a
Infla
mm
ato
ry_
Cyto
kin
es_
&_
Re
ce
pto
rs9
3S
AB
CF
1B
CL
6B
LR
1C
3C
4A
C5
CC
L1
CC
L1
1C
CL
13
CC
L1
5C
CL
16
CC
L1
7C
CL
18
CC
L1
9C
CL
2C
CL
20
CC
L2
1C
CL
23
CC
L2
4C
CL
25
CC
L2
6C
CL
3C
CL
4C
CL
5C
CL
7C
CL
8C
CR
1C
CR
2C
CR
3C
CR
4C
CR
5
Ino
sito
l_p
ho
sp
ha
te_
me
tab
olis
m_
KE
GG
51
KC
9o
rf9
5D
YR
K4
EIF
2A
K3
FN
3K
IMP
A1
IMP
A2
INP
P1
INP
P4
AIN
PP
4B
INP
P5
AIN
PP
5B
INP
P5
EIN
PP
L1
IPM
KIS
YN
A1
ITG
B1
BP
3IT
PK
AIT
PK
BM
INP
P1
MIO
XO
CR
LP
IB5
PA
PIK
3C
3P
IK3
CA
PIK
3C
BP
IK3
CD
PIK
3C
GP
IK4
CA
PIK
4C
BP
IP5
K1
AP
IP5
K1
B
Insu
lin_
Sig
na
ling
_P
ath
wa
y1
71
SA
CA
CA
AC
AC
BA
CO
X1
AD
RB
3A
EB
P1
AH
SG
AK
T1
AK
T2
AK
T3
AN
GA
RA
F1
BA
DB
CL
2L
1B
RA
FC
AL
M1
CA
LM
2C
AL
M3
CA
LM
L3
CA
LM
L6
CA
P1
CB
LC
BL
BC
BL
CC
EB
PA
CE
BP
BC
EB
PD
CR
KC
RK
LC
SN
2D
FD
OK
1
Inte
rfe
ron
84
SA
DA
RC
NT
FR
CR
LF
2C
SF
2R
AC
SF
3R
CX
CL
10
EB
I3F
3F
ND
C6
G1
P2
G1
P3
IFI1
6IF
I27
IFI3
0IF
I35
IFI4
4IF
I44
LIF
IH1
IFIT
1IF
IT1
LIF
IT2
IFIT
3IF
ITM
1IF
ITM
2IF
NA
1IF
NA
14
IFN
A2
IFN
A2
1IF
NA
4IF
NA
5IF
NA
6
Inte
rfe
ron
_a
,b_
Re
sp
on
se
96
SA
DA
RA
RL
5A
TF
5B
2M
BA
G3
BS
T2
C1
orf
29
C6
orf
85
CA
SP
1C
AV
1C
BF
BC
DK
N1
BC
NP
CO
L1
6A
1C
XC
L1
0D
AD
1D
IAB
LO
DN
AJB
2F
LJ4
22
80
G1
P3
GB
P1
GB
P2
GC
H1
GIP
2H
19
HL
A-A
HL
A-B
HO
XB
2H
SP
A6
IFI1
6IF
I27
Inte
rle
ukin
s_
an
d_
Re
ce
pto
rs7
1S
IL1
0R
BIL
11
IL1
1R
AIL
12
AF
IL1
IL1
0IL
10
RA
IL1
2B
IL1
2R
B1
IL1
2R
B2
IL1
3IL
13
RA
1IL
13
RA
2IL
14
IL1
5IL
15
RA
IL1
6IL
17
IL1
7B
IL1
7C
IL1
7E
IL1
7F
IL1
7R
IL1
8IL
18
BP
IL1
8R
1IL
18
RA
PIL
19
IL1
AIL
1B
IL-1
H1
Inva
siv
en
ess_
Ge
ne
_S
ign
atu
re1
89
Liu
et
al.
CL
TC
LD
HA
DN
AJB
1P
GK
1C
IRB
PS
SR
1C
OP
B2
PL
P2
RA
D2
3B
PS
MA
5S
H3
BG
RL
EM
P1
SN
UR
FS
NR
PN
ICM
TC
10
OR
F7
LT
FD
PF
2JT
V1
MG
PG
NP
DA
1K
LF
10
NS
FM
AP
K1
4S
TK
39
RN
F8
HS
2S
T1
CN
OT
4S
TC
2S
TA
MS
RP
54
JA
K_
ST
AT
_S
ign
alin
g_
Pa
thw
ay
17
9S
A2
MA
KT
1A
KT
2A
KT
3A
PS
BC
L2
L1
CB
LC
BL
BC
BL
CC
CN
D1
CC
ND
2C
CN
D3
CD
KN
1A
CE
BP
BC
ISH
CL
CF
1C
NT
FC
NT
FR
CR
EB
BP
CR
KC
RK
LC
RL
F2
CR
PC
SF
1R
CS
F2
CS
F2
RA
CS
F2
RB
CS
F3
CS
F3
RC
SN
2C
TF
1
MA
P_
Kin
ase
_S
ign
alin
g_
Pa
thw
ay
97
SA
OP
2A
RA
F1
AT
F2
BR
AF
CC
NA
1C
CN
A2
CC
NB
1C
CN
B2
CC
ND
1C
CN
D2
CC
ND
3C
CN
E1
CC
NE
2C
DC
42
CD
K2
CD
K4
CD
K6
CD
KN
1A
CD
KN
1B
CD
KN
1C
CD
KN
2A
CD
KN
2B
CD
KN
2C
CH
UK
CO
L1
A1
CR
EB
1C
RE
BB
PD
LK
1D
US
P1
E2
F1
EG
FR
Me
tab
olis
m_
of_
xe
no
bio
tics_
by_
cyto
ch
rom
e_
P4
50
_K
EG
G5
9K
AD
H1
CA
DH
4A
DH
5A
DH
6A
DH
7A
DH
FE
1A
KR
1C
2A
KR
1C
3A
KR
1C
4A
LD
H1
A3
AL
DH
3A
1A
LD
H3
B1
AL
DH
3B
2C
YP
1A
1C
YP
1A
2C
YP
1B
1C
YP
2B
6C
YP
2C
18
CY
P2
C1
9C
YP
2C
8C
YP
2C
9C
YP
2E
1C
YP
2F
1C
YP
2S
1C
YP
3A
4C
YP
3A
43
CY
P3
A5
CY
P3
A7
DH
DH
EP
HX
1G
ST
A1
Me
tal_
Tra
nsp
ort
_a
nd
_H
om
eo
sta
sis
94
SA
BC
B1
0A
BC
B7
AC
O1
AL
AS
1A
TO
X1
AT
P7
AA
TP
7B
B2
MC
AL
RC
AT
CC
SC
D1
63
CP
CY
BR
D1
DIO
1D
NA
JA
1E
GR
1F
EC
HF
MO
3F
OS
FR
DA
FT
H1
FT
LG
AS
1G
PX
1G
PX
2G
PX
3G
PX
4G
SR
GS
SG
ST
A1
Me
tallo
pro
tea
se
s3
4p
rese
nt_
stu
dy
MM
P1
MM
P1
0M
MP
11
MM
P1
2M
MP
13
MM
P1
4M
MP
15
MM
P1
6M
MP
17
MM
P1
9M
MP
19
///
LM
MP
2M
MP
20
MM
P2
1M
MP
23
B /
//M
MP
24
MM
P2
5M
MP
26
MM
P2
7M
MP
28
MM
P3
MM
P7
MM
P8
MM
P9
MP
P1
MP
P2
MP
P3
MP
P4
MP
P5
MP
P6
MP
P7
Me
tasta
sis
_a
de
no
ca
rc_
dn
34
msig
db
CP
N1
HR
44
KC
NA
B1
RO
RB
PG
K1
AS
PA
ST
AC
RU
NX
1R
OR
1M
YL
2P
CD
H1
1X
MY
LK
CN
N1
PB
X2
RN
AS
E1
MA
OB
AC
AD
SB
PL
P1
CH
RN
A5
NR
4A
1N
CA
PH
ZN
F1
48
P2
RX
1IN
PP
5E
PT
NN
R2
F2
JM
JD
1C
FX
NP
DE
6A
PR
KG
2R
AB
30
Me
tasta
sis
_a
de
no
ca
rc_
up
14
msig
db
PR
MT
1C
OL
1A
1F
BL
N2
MA
D2
L1
PS
EN
2S
TR
A1
3F
AS
NC
OL
1A
2S
NR
PF
CO
X7
BG
PI
DH
PS
P4
HB
EL
F4
mT
OR
_sig
na
ling
_p
ath
wa
y_
KE
GG
49
KA
KT
1A
KT
2A
KT
3B
RA
FC
AB
39
DD
IT4
EIF
4B
EIF
4E
EIF
4E
2E
IF4
EB
P1
FIG
FF
RA
P1
GB
LH
IF1
AIG
F1
INS
KIA
A1
30
3L
YK
5M
AP
K1
MA
PK
3P
DP
K1
PG
FP
IK3
CA
PIK
3C
BP
IK3
CD
PIK
3C
GP
IK3
R1
PIK
3R
2P
IK3
R3
PIK
3R
5P
RK
AA
1
Na
tura
l_kill
er_
ce
ll_m
ed
iate
d_
cyto
toxic
ity_
KE
GG
11
8K
BID
CA
SP
3C
D2
44
CD
24
7C
D4
8C
HP
CS
F2
FA
SF
AS
LG
FC
ER
1G
FC
GR
3A
FY
NG
RB
2G
ZM
BH
CS
TH
LA
-AH
LA
-BH
LA
-CH
LA
-EH
LA
-GH
RA
SIC
AM
1IC
AM
2IF
NA
1IF
NA
10
IFN
A1
3IF
NA
14
IFN
A1
6IF
NA
17
IFN
A2
IFN
A2
1
Ne
uro
scie
nce
_Io
n_
Ch
an
ne
ls_
&_
Tra
nsp
ort
ers
10
4S
AC
CN
1A
CC
N2
AC
CN
3A
PO
EA
TP
1A
1A
TP
1B
1A
TP
2A
1A
TP
2B
1A
TP
2B
4A
TP
4A
AT
P5
BA
TP
6V
0A
2A
TP
6V
0D
1A
TP
6V
1A
AT
P6
V1
B2
AT
P7
AA
TP
7B
CA
CN
A1
BC
AC
NA
1C
CA
CN
A1
HC
AC
NA
1S
CA
CN
B1
CA
CN
B2
CA
CN
B3
CA
CN
B4
CA
CN
G2
CE
TP
CF
TR
CL
CA
1C
LC
N1
CL
CN
2
Ne
uro
tra
nsm
itte
r_R
ece
pto
rs_
an
d_
Re
gu
lato
rs1
07
SA
BA
TA
CH
EA
NX
A9
BA
IAP
3B
RS
3B
ZR
PC
AP
ON
CC
KA
RC
CK
BR
CH
AT
CH
RM
1C
HR
M2
CH
RM
3C
HR
NA
1C
HR
NA
2C
HR
NA
3C
HR
NA
4C
HR
NA
5C
HR
NA
6C
HR
NA
7C
HR
NB
1C
HR
NB
2C
HR
NB
4C
HR
ND
CH
RN
EC
HR
NG
CO
LQ
CO
MT
DR
D1
DR
D2
DR
D3
NF
kB
_S
ign
alin
g_
Pa
thw
ay
11
3S
AG
TA
KT
1A
PO
L3
AT
F1
AT
F2
BC
L1
0B
CL
3B
FB
IRC
2C
3C
AR
D1
0C
AR
D1
1C
AR
D1
4C
AR
D4
CA
SP
1C
AS
P8
CC
L2
CF
LA
RC
HU
KC
SF
2C
SF
3C
TL
2C
XX
C5
EC
M1
ED
AR
AD
DE
DG
2E
GR
1E
LK
1F
2R
FA
DD
FO
S
Nitric_
Oxid
e1
73
SA
BC
C1
AD
MA
GT
R1
AK
T1
AL
AS
2A
LO
X1
2A
PO
EA
RG
2A
TO
X1
BC
L2
BN
IP3
CA
MK
1C
AT
CC
L2
CC
L3
CC
L5
CC
NA
1C
CS
CD
KN
1A
CF
TR
CO
L1
A1
CO
L2
A1
CO
L3
A1
CS
F1
CX
CL
2C
YB
AC
YG
BC
YP
19
CY
P2
D6
CY
P3
A4
DD
AH
2
Nitro
ge
n_
me
tab
olis
m_
KE
GG
24
KA
MT
AS
NS
CA
1C
A1
1C
A1
2C
A1
3C
A1
4C
A2
CA
3C
A4
CA
5A
CA
5B
CA
6C
A7
CA
8C
A9
CP
S1
CT
HG
LS
GL
S2
GL
UD
1G
LU
D2
GL
UL
HA
L
No
tch
_S
ign
alin
g_
Pa
thw
ay
13
0S
AD
AM
10
AD
AM
17
AE
SA
PH
1A
AP
H-1
AA
XIN
1C
BL
CC
ND
1C
CN
E1
CD
44
CD
C1
6C
DK
N1
AC
DK
N1
BC
FL
AR
CH
UK
CIR
CR
EB
BP
CT
BP
1C
TB
P2
CT
NN
B1
DL
L1
DL
L3
DL
L4
DT
X1
DT
X2
DT
X3
DT
X3
LD
TX
4D
VL
1D
VL
2D
VL
3
Nu
cle
ar_
Re
ce
pto
rs_
an
d_
Co
reg
ula
tors
11
4S
AH
RA
RA
RN
TB
RD
8C
1D
CA
RM
1C
OP
S2
CR
EB
BP
CR
SP
2C
RS
P6
DD
X5
DM
AP
1E
RF
ES
R1
ES
R2
ES
RR
AE
SR
RB
ES
RR
GH
DA
C1
HD
AC
2H
DA
C3
HD
AC
4H
DA
C5
HD
AC
6H
DA
C7
AH
MG
A1
HN
F4
AH
NF
4G
HT
AT
IPIT
GB
3B
PM
ED
12
Oxid
ative
_p
ho
sp
ho
ryla
tio
n_
KE
GG
11
5K
AT
P1
2A
AT
P4
AA
TP
4B
AT
P5
A1
AT
P5
BA
TP
5C
1A
TP
5D
AT
P5
EA
TP
5F
1A
TP
5G
1A
TP
5G
2A
TP
5G
3A
TP
5H
AT
P5
IA
TP
5J
AT
P5
J2
AT
P5
LA
TP
5O
AT
P6
AP
1A
TP
6V
0A
1A
TP
6V
0A
2A
TP
6V
0A
4A
TP
6V
0B
AT
P6
V0
CA
TP
6V
0D
1A
TP
6V
0D
2A
TP
6V
0E
AT
P6
V1
AA
TP
6V
1B
1A
TP
6V
1B
2A
TP
6V
1C
1
Oxid
ative
_S
tre
ss_
an
d_
An
tio
xid
an
t_D
efe
nse
84
SA
LB
AL
OX
12
AN
GP
TL
7A
OX
1A
PO
EA
TO
X1
BN
IP3
CA
TC
CL
5C
CS
CS
DE
1C
YB
AC
YG
BD
GK
KD
HC
R2
4D
UO
X1
DU
OX
2D
US
P1
EP
HX
2E
PX
FO
XM
1G
LR
X2
GP
R1
56
GP
X1
GP
X2
GP
X3
GP
X4
GP
X5
GP
X6
GP
X7
GS
R
p5
3_
Sig
na
ling
_P
ath
wa
y1
13
SA
AT
FA
PA
F1
AT
MA
TR
BA
G1
BA
I1B
AK
1B
AP
1B
AX
BC
L2
BC
L2
A1
BID
BIR
C5
BN
IP3
BR
CA
1B
RC
A2
BT
G2
CA
SP
2C
AS
P9
CC
NE
2C
CN
G2
CC
NH
CD
C2
CD
C2
5A
CD
C2
5C
CD
K4
CD
K7
CD
KN
1A
CD
KN
2A
CH
EK
1C
HE
K2
Pa
sse
rin
i_P
rolif
era
tio
n6
5m
sig
db
TG
FB
2C
BF
A2
T2
PD
GF
RA
BA
P1
TS
HR
TS
PA
N5
ED
N1
TO
B1
IGF
BP
7F
SC
N1
TIM
P1
TU
SC
2C
LK
1E
TS
1B
CL
2E
GF
NU
DC
CU
L1
PR
KC
AH
OX
C1
0T
NF
SF
4A
RH
GE
F1
TN
FS
F1
1V
HL
TA
CS
TD
2C
DK
N2
AA
DA
MT
S8
NF
2IL
10
FG
FR
1O
PL
AM
P3
Ph
osp
ha
tase
s1
05
pre
se
nt_
stu
dy
RP
S2
7A
PT
PR
AP
TP
RB
PT
PR
CP
TP
RD
PT
PR
EP
TP
RF
PT
PR
GP
TP
RH
PT
PR
JP
TP
RK
PT
PR
MP
TP
RN
PT
PR
N2
PT
PR
OP
TP
RQ
PT
PR
RP
TP
RS
PT
PR
TP
TP
RU
PT
PR
VP
TP
RZ
1P
TP
N1
PT
PN
2P
TP
N3
PT
PN
4P
TP
N5
PT
PN
6P
TP
N7
PT
PN
9P
TP
N1
1
PI3
K-A
KT
_S
ign
alin
g_
Pa
thw
ay
11
3S
AD
AR
AIC
DA
AK
T1
AK
T2
AK
T3
AP
CA
PP
LA
SA
H1
AX
IN1
BA
DB
TK
CA
SP
9C
CN
D1
CD
14
CD
C4
2C
DK
N1
BC
HU
KC
SN
K2
A1
CT
MP
CT
NN
B1
CU
TL
1E
IF2
AK
2E
IF3
S1
0E
IF4
A1
EIF
4B
EIF
4E
EIF
4E
BP
1E
IF4
G1
EL
K1
FA
SL
GF
KB
P1
A
PP
AR
_sig
na
ling
_p
ath
wa
y_
KE
GG
67
KA
CA
A1
AC
AD
LA
CA
DM
AC
OX
1A
CO
X2
AC
OX
3A
CS
L1
AC
SL
3A
CS
L4
AC
SL
5A
CS
L6
AD
IPO
QA
NG
PT
L4
AP
OA
1A
PO
A2
AP
OA
4A
PO
C3
AQ
P7
CD
36
CP
T1
AC
PT
1B
CP
T1
CC
PT
2C
YP
27
A1
CY
P4
A1
1C
YP
7A
1C
YP
8B
1D
BI
FA
BP
1F
AB
P2
FA
BP
3
Pro
life
ratio
n_
Sig
na
ture
51
Wh
itfie
ld e
t a
l.B
IRC
5A
UR
KB
CD
C6
CK
S2
TR
IPC
HE
K1
PT
TG
1D
NM
T1
NA
SP
UN
GC
DC
7F
EN
1M
CM
3M
CM
4M
CM
5M
CM
6O
RC
1L
PC
NA
PR
IM1
RF
C1
RR
M1
RR
M2
TO
P2
AM
AD
2L
1C
EN
PE
BU
B1
CT
PS
DH
FR
TY
MS
CC
NA
2C
CN
B1
Pro
tea
so
me
_K
EG
G3
1K
PS
MA
1P
SM
A2
PS
MA
3P
SM
A4
PS
MA
5P
SM
A6
PS
MA
7P
SM
B1
PS
MB
2P
SM
B3
PS
MB
4P
SM
B5
PS
MB
6P
SM
B7
PS
MC
1P
SM
C2
PS
MC
3P
SM
C4
PS
MC
5P
SM
C6
PS
MD
1P
SM
D1
1P
SM
D1
2P
SM
D1
3P
SM
D1
4P
SM
D2
PS
MD
3P
SM
D4
PS
MD
6P
SM
D7
PS
MD
8
Re
cu
rre
nce
_S
co
re1
6E
SR
2P
GR
BC
L2
SC
UB
E2
MK
I67
MY
BL
2B
IRC
5C
CN
B1
AU
RK
AE
RB
B2
GR
B7
MM
P1
1C
TS
L2
GS
TM
1B
AG
1C
D6
8
Re
gu
latio
n_
of_
actin
_cyto
ske
leto
n_
KE
GG
20
1K
AB
I2A
CT
BA
CT
C1
AC
TG
1A
CT
N1
AC
TN
2A
CT
N3
AC
TN
4A
PC
AP
C2
AR
HG
EF
1A
RH
GE
F1
2A
RH
GE
F4
AR
HG
EF
6A
RH
GE
F7
AR
PC
1A
AR
PC
1B
AR
PC
2A
RP
C3
AR
PC
4A
RP
C5
AR
PC
5L
BA
IAP
2B
CA
R1
BD
KR
B2
BR
AF
CD
14
CD
C4
2C
FL
1C
FL
2C
HR
M1
Re
gu
latio
n_
of_
au
top
ha
gy_
KE
GG
28
KA
TG
12
AT
G3
AT
G5
AT
G7
BE
CN
1G
AB
AR
AP
GA
BA
RA
PLI
FN
A1
IFN
A1
0IF
NA
13
IFN
A1
4IF
NA
16
IFN
A1
7IF
NA
2IF
NA
21
IFN
A4
IFN
A5
IFN
A6
IFN
A7
IFN
A8
IFN
GIN
SP
IK3
C3
PIK
3R
4P
RK
AA
1P
RK
AA
2U
LK
1U
LK
2
Rib
ofla
vin
_m
eta
bo
lism
_K
EG
G1
6K
AC
P1
AC
P2
AC
P5
AC
P6
AC
PP
AC
PT
EN
PP
1E
NP
P2
EN
PP
3F
LA
D1
MT
MR
1M
TM
R2
MT
MR
6P
HP
T1
RF
KT
YR
Rib
oso
me
_K
EG
G8
6K
C1
5o
rf1
5F
AU
LO
C4
41
90
7M
RP
L1
3R
PL
10
RP
L1
0A
RP
L1
0L
RP
L1
1R
PL
12
RP
L1
3R
PL
13
AR
PL
14
RP
L1
5R
PL
17
RP
L1
8R
PL
18
AR
PL
19
RP
L2
1R
PL
22
RP
L2
3R
PL
23
AR
PL
24
RP
L2
6R
PL
26
L1
RP
L2
7R
PL
27
AR
PL
28
RP
L2
9R
PL
3R
PL
30
RP
L3
1
Ro
tte
rda
m_
sig
na
ture
68
Ja
nse
n e
t a
l.P
PP
1C
CA
BL
IM1
PS
MC
2C
BX
3 /
// L
OCA
RH
GD
IBZ
FP
36
L2
SM
C4
PA
RP
4P
LK
1Y
IF1
AT
NF
SF
10
SL
C3
5A
1F
KB
P2
DU
SP
4C
11
orf
9C
11
orf
51
EE
F1
A2
MY
H2
CN
KS
R1
FE
N1
NE
UR
LC
CN
E2
GA
S2
IL1
8M
MP
23
B /
//H
IST
1H
4H
CA
PN
2T
NF
SF
13
//H
DG
FR
P3
CD
44
CE
P5
7
Sh
ep
ard
_ce
ll_p
rolif
era
tio
n2
32
msig
db
CK
S1
BC
DK
6C
BF
A2
T2
TC
F8
CT
NN
BIP
1C
6o
rf1
08
ISG
20
RE
GL
PD
AP
2C
DK
9P
IM2
VT
I1B
GP
C4
BU
B3
CH
RM
1M
NT
CT
F1
CR
IP1
DD
5A
DR
A1
BR
PS
4X
PD
AP
1Z
NF
18
7E
RF
CD
C2
7T
AC
ST
D2
EV
I5C
HR
M4
ER
GD
TY
MK
SY
K
Sh
ep
ard
_n
eg
_re
g_
of_
ce
ll_p
rolif
era
tio
n1
16
msig
db
DL
EC
1T
P5
3I1
1C
CL
23
CD
33
RA
RR
ES
3S
SH
3B
P1
AT
P8
A2
SS
TR
5IG
FB
P7
CH
EK
1C
DC
6M
NT
MU
C1
2IL
1B
TIE
GA
PR
INC
OL
18
A1
AD
AM
TS
8C
NO
T8
MX
D4
CT
BP
2E
MP
3C
TB
P1
SS
TR
4T
M4
SF
4H
GS
HB
P1
7O
SM
CD
KN
2D
PM
P2
2W
AR
S
Sig
na
l_T
ran
sd
uctio
n_
in_
Ca
nce
r9
8S
AT
F2
BC
L2
BC
L2
A1
BC
L2
L1
BIR
C1
BIR
C2
BIR
C3
BM
P4
BR
CA
1C
CN
D1
cd
k4
CD
KN
1A
CD
KN
1B
CD
KN
1C
CD
KN
2A
CD
KN
2B
CD
KN
2C
CD
KN
2D
CO
L1
A1
CS
N2
CT
SD
CX
CL
9D
US
P1
ED
N1
EG
FR
EG
R1
EN
1E
NP
P2
EP
OF
N1
FO
LH
1
Sig
na
l_T
ran
sd
uctio
n_
Pa
thw
ay_
Fin
de
r1
14
SA
2M
AT
F2
BA
XB
CL
2B
CL
2A
1B
CL
2L
1B
IRC
1B
IRC
2B
IRC
3B
IRC
5B
MP
2B
MP
4B
RC
A1
CC
L2
CC
L2
0C
CN
D1
CD
5C
DK
2cd
k4
CD
KN
1A
CD
KN
1B
CD
KN
1C
CD
KN
2A
CD
KN
2B
CD
KN
2C
CD
KN
2D
CD
X1
CE
BP
BC
SF
2C
SN
2C
TS
D
Sp
hin
go
lipid
_m
eta
bo
lism
_K
EG
G3
7K
AR
SA
AR
SD
AR
SE
AS
AH
1B
4G
AL
T6
CE
RK
DE
GS
1D
EG
S2
EN
PP
7F
VT
1G
AL
3S
T1
GA
LC
GB
AG
LA
GL
B1
LC
TM
GC
26
96
3N
EU
1N
EU
2N
EU
3N
EU
4P
HC
AP
PA
P2
AP
PA
P2
BP
PA
P2
CS
GP
L1
SG
PP
1S
GP
P2
SM
PD
1S
MP
D2
SM
PD
3
Str
ess_
&_
To
xic
ity_
Pa
thw
ay_
Fin
de
r9
6S
AN
XA
5A
TM
BA
XB
CL
2L
1B
CL
2L
2C
AS
P1
CA
SP
10
CA
SP
8C
CL
21
CC
L4
CC
ND
1C
CN
G1
CH
EK
2C
RY
AB
CS
F2
CX
CL
10
CY
P1
A1
CY
P1
B1
CY
P2
E1
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Str
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Da
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96
SA
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11
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11
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NA
JA
1D
NA
JA
2
T_
ce
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pto
r_sig
na
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wa
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KE
GG
92
KA
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CL
10
CA
RD
11
CB
LC
BL
BC
BL
CC
D2
47
CD
28
CD
3D
CD
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CD
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CD
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D4
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GC
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AC
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DC
42
CD
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CD
33
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12
TG
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16
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AA
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10
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25
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36
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15
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CD
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69
CD
80
CD
86
CE
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BC
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46
39
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44
Tig
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GG
11
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42
CD
K4
CG
NC
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10
CL
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11
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DN
14
CL
DN
15
CL
DN
16
CL
DN
17
CL
DN
18
CL
DN
19
CL
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2C
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TN
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NF
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FR
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9T
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SF
10
TN
FS
F1
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18
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FS
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TN
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FS
F8
TN
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To
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KE
GG
90
KA
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10
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14
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17
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8
To
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73
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10
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36
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59
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44
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40
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na
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61
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61
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16
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21
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18
CL
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19
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CN
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10
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23
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69
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19
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20
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22
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23
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3
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24
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25
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5
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26
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27
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3
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Co
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10
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10
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12
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12
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13
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15
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17
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19
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20
Co
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65
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13
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RE
11
AM
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56
SC
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5A
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5A
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6A
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6A
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EC
M_
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82
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RP
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RP
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2
EC
M_
me
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ran
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38
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55
30
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40
26
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39
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15
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17
EC
M_
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61
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10
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96
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12
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14
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19
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68
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GR
M3
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M4
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M5
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M6
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M7
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97
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31
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74
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Ge
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32
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40
77
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45
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27
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12
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11
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19
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11
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Sig
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99
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HM
74
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16
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96
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10
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12
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10
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HB
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FIG
F1
IGF
2IL
10
IL1
1IL
12
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18
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AIL
1B
IL2
IL3
IL4
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AIN
HB
AIN
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55
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36
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16
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3A
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T7
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7B
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8B
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2
Hyp
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48
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30
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43
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pa
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Infla
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CL
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CL
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L9
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4E
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ER
GIF
NA
2IF
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IL1
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10
RA
IL1
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BIL
11
IL1
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AIL
12
AIL
12
B
Ino
sito
l_p
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sp
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tab
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m_
KE
GG
51
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_P
ath
wa
y1
71
SD
OK
2D
OK
3D
OK
4D
OK
5D
OK
6D
US
P1
4E
IF2
B1
EIF
4E
EIF
4E
2E
IF4
EB
P1
EL
K1
ER
CC
1E
XO
C7
FA
SN
FB
P1
FB
P2
FL
OT
1F
LO
T2
FO
SF
OX
O1
AF
RA
P1
FR
S2
FR
S3
G6
PC
G6
PD
GA
B1
GC
GG
CK
GP
D1
GP
D2
GR
B1
0
Inte
rfe
ron
84
SIF
NA
8IF
NA
R1
IFN
AR
2IF
NB
1IF
NE
1IF
NG
IFN
GR
1IF
NG
R2
IFN
KIF
NW
1IF
RD
1IF
RD
2IL
10
RA
IL1
0R
BIL
11
RA
IL1
2B
IL1
3R
A1
IL1
5IL
20
RA
IL2
1R
IL2
2R
A2
IL2
8A
IL2
8R
AIL
29
IL2
RB
IL2
RG
IL3
1R
AIL
3R
AIL
4R
IL5
RA
IL6
Inte
rfe
ron
_a
,b_
Re
sp
on
se
96
SIF
I30
IFI3
5IF
I44
IFIT
1IF
IT2
IFIT
4IF
IT5
IFIT
M1
IFIT
M2
IFN
A1
IFN
AR
1IF
NA
R2
IFN
B1
IFN
GIF
NW
1IF
RD
1IF
RD
2IL
2R
BIR
F1
IRF
2IR
F3
IRF
5IR
F7
ISG
20
ISG
F3
GIT
IH2
JA
K1
KIA
A1
26
8K
LK
3L
AM
P1
MA
L
Inte
rle
ukin
s_
an
d_
Re
ce
pto
rs7
1S
IL1
HY
1IL
1R
2IL
1R
AP
IL1
RA
PL
1IL
1R
AP
L2
IL1
RL
1IL
1R
L2
IL1
RN
IL2
IL2
0IL
20
RA
IL2
1IL
21
RIL
22
IL2
2R
IL2
2R
A2
IL2
3A
IL2
4IL
26
IL2
RA
IL2
RB
IL2
RG
IL3
IL3
RA
IL4
IL4
RIL
5IL
5R
AIL
6IL
6R
IL6
ST
Inva
siv
en
ess_
Ge
ne
_S
ign
atu
re1
89
Liu
et
al.
BC
L2
EL
P4
RN
F3
1IS
GF
3G
WF
DC
2M
AP
TC
EB
PD
KL
HL
20
MM
P7
TH
EM
2M
LF
1P
EB
P1
ZB
TB
20
AT
XN
3S
CG
NK
DE
LR
3M
ET
TL
7A
EC
OP
ND
EL
1P
RS
S1
6F
LN
BV
IL2
AT
ICG
OL
GA
8A
RE
EP
5P
AK
2C
1O
RF
63
SW
AP
70
EIF
4E
2P
LA
AC
XC
L2
JA
K_
ST
AT
_S
ign
alin
g_
Pa
thw
ay
17
9S
CX
CL
9E
GF
RE
P3
00
EP
OE
PO
RF
2F
2R
FC
ER
1A
FC
ER
2F
CG
R1
AG
1P
2G
1P
3G
AT
A3
GB
P1
GH
RG
RB
2H
MG
A1
IFN
A1
IFN
A1
0IF
NA
13
IFN
A1
4IF
NA
16
IFN
A1
7IF
NA
2IF
NA
21
IFN
A4
IFN
A5
IFN
A6
IFN
A7
IFN
A8
IFN
AR
1
MA
P_
Kin
ase
_S
ign
alin
g_
Pa
thw
ay
97
SE
GR
1E
LK
1E
LK
4E
NP
P2
ET
S1
ET
S2
FO
SG
RB
2H
RA
SH
SP
A5
HS
PB
1JN
KK
1)
JU
NK
RA
S2
KS
RM
AD
H4
MA
P2
K1
MA
P2
K1
IP1M
AP
2K
2M
AP
2K
3M
AP
2K
4M
AP
2K
5M
AP
2K
6M
AP
2K
7M
AP
3K
1M
AP
3K
11
MA
P3
K1
4M
AP
3K
2M
AP
3K
3M
AP
3K
4M
AP
3K
5
Me
tab
olis
m_
of_
xe
no
bio
tics_
by_
cyto
ch
rom
e_
P4
50
_K
EG
G5
9K
GS
TA
2G
ST
A3
GS
TA
4G
ST
A5
GS
TK
1G
ST
M1
GS
TM
2G
ST
M3
GS
TM
4G
ST
M5
GS
TO
1G
ST
O2
GS
TP
1G
ST
T1
GS
TT
2G
ST
Z1
MG
ST
1M
GS
T2
MG
ST
3U
GT
1A
6U
GT
2A
1U
GT
2B
10
UG
T2
B1
1U
GT
2B
15
UG
T2
B1
7U
GT
2B
28
UG
T2
B4
UG
T2
B7
Me
tal_
Tra
nsp
ort
_a
nd
_H
om
eo
sta
sis
94
SH
AM
PH
DH
EP
HH
FE
HIF
1A
HM
OX
1H
MO
X2
HP
HP
XH
SP
A1
AH
SP
A5
HS
PA
9B
HS
PB
1H
SP
D1
HS
PH
1IR
EB
2JU
NL
OX
LT
FM
FI2
MP
OM
T2
AM
T3
MT
F1
MY
CN
OS
1P
MP
22
PO
PD
C2
PO
RP
RD
X4
SE
LM
Me
tallo
pro
tea
se
s3
4re
se
nt_
stu
dM
PP
E1
MP
PE
D1
MP
PE
D2
Me
tasta
sis
_a
de
no
ca
rc_
dn
34
msig
db
RB
M5
AB
LIM
1D
LG
3
Me
tasta
sis
_a
de
no
ca
rc_
up
14
msig
db
mT
OR
_sig
na
ling
_p
ath
wa
y_
KE
GG
49
KP
RK
AA
2R
HE
BR
ICT
OR
RP
S6
RP
S6
KA
1R
PS
6K
A2
RP
S6
KA
3R
PS
6K
A6
RP
S6
KB
1R
PS
6K
B2
ST
K1
1T
SC
1T
SC
2U
LK
1U
LK
2V
EG
FV
EG
FB
VE
GF
C
Na
tura
l_kill
er_
ce
ll_m
ed
iate
d_
cyto
toxic
ity_
KE
GG
11
8K
IFN
A4
IFN
A5
IFN
A6
IFN
A7
IFN
A8
IFN
AR
1IF
NA
R2
IFN
B1
IFN
GIF
NG
R1
IFN
GR
2IT
GA
LIT
GB
2K
IR2
DL
1K
IR3
DL
1K
LR
C1
KL
RC
2K
LR
C3
KL
RD
1K
RA
SL
AT
LC
KL
CP
2M
AP
2K
1M
AP
2K
2M
AP
K1
MA
PK
3M
ICA
MIC
BN
CR
1N
CR
2
Ne
uro
scie
nce
_Io
n_
Ch
an
ne
ls_
&_
Tra
nsp
ort
ers
10
4S
CL
CN
3C
LC
N4
CL
CN
5C
LC
N6
CL
CN
7C
LIC
1C
LIC
2K
CN
A1
KC
NA
2K
CN
A3
KC
NA
4K
CN
A5
KC
NB
1K
CN
B2
KC
NC
1K
CN
C4
KC
ND
1K
CN
D2
KC
NE
1K
CN
F1
KC
NG
1K
CN
H1
KC
NH
2K
CN
J1
KC
NJ1
1K
CN
J3
KC
NJ4
KC
NJ5
KC
NJ6
KC
NM
B1
KC
NN
1
Ne
uro
tra
nsm
itte
r_R
ece
pto
rs_
an
d_
Re
gu
lato
rs1
07
SG
AB
RA
1G
AB
RA
2G
AB
RA
3G
AB
RB
1G
AB
RB
2G
AB
RD
GA
BR
EG
AB
RG
1G
AB
RG
2G
AB
RP
GA
BR
QG
AB
RR
2G
AD
1G
AD
2G
AL
R1
GA
LR
2G
AL
R3
GC
H1
GC
HF
RG
LR
A1
GL
RA
2G
LR
A3
GP
R1
0G
PR
10
3G
PR
14
7G
PR
24
GP
R7
3G
PR
73
L1
GP
R7
4G
PR
83
GR
IA1
NF
kB
_S
ign
alin
g_
Pa
thw
ay
11
3S
GJA
1G
PR
89
HM
OX
1H
NL
FH
TR
2B
ICA
M1
IFN
A1
IFN
B1
IFN
GIK
BK
BIK
BK
EIK
BK
GIL
10
IL1
AIL
1B
IL1
R1
IL6
IL8
IRA
K1
IRA
K2
JU
NL
ITA
FL
TA
LT
BR
MA
LT
1M
AP
2K
3M
AP
2K
4M
AP
2K
6M
AP
3K
1M
AP
3K
14
MA
P3
K3
Nitric_
Oxid
e1
73
SD
DIT
3D
LG
4D
NC
L1
DU
OX
1D
UO
X2
DU
SP
1E
DN
1E
DN
RB
EG
FR
EG
R1
EP
OE
PX
FL
J3
71
74
FL
T1
FM
R1
FN
1F
OX
M1
FT
LG
AD
D4
5A
GA
DD
45
BG
CH
1G
CH
FR
GC
LC
GC
LM
GL
AG
LR
X2
GP
R1
56
GP
X1
GP
X2
GP
X3
GP
X4
Nitro
ge
n_
me
tab
olis
m_
KE
GG
24
K
No
tch
_S
ign
alin
g_
Pa
thw
ay
13
0S
EP
30
0F
IGF
FO
SF
OS
L1
FZ
D1
FZ
D1
0F
ZD
2F
ZD
3F
ZD
4F
ZD
6F
ZD
7F
ZD
8F
ZD
9G
BP
2G
CN
5L
2G
LI1
GL
I2G
LI3
GS
K3
BH
DA
C1
HD
AC
2H
ES
1H
ES
5H
ES
6H
EY
1H
EY
2H
EY
LH
OX
B4
HR
IFN
GIL
17
B
Nu
cle
ar_
Re
ce
pto
rs_
an
d_
Co
reg
ula
tors
11
4S
ME
D4
ML
R2
MT
A1
MY
ST
4N
CO
A1
NC
OA
2N
CO
A3
NC
OA
4N
CO
A6
NC
OA
6IP
NC
OR
1N
CO
R2
NF
KB
2N
ON
ON
OT
CH
2N
PM
1N
R0
B1
NR
0B
2N
R1
D1
NR
1D
2N
R1
H2
NR
1H
3N
R1
H4
NR
1I2
NR
1I3
NR
2C
1N
R2
C2
NR
2E
1N
R2
E3
NR
2F
1N
R2
F2
Oxid
ative
_p
ho
sp
ho
ryla
tio
n_
KE
GG
11
5K
AT
P6
V1
C2
AT
P6
V1
DA
TP
6V
1E
1A
TP
6V
1E
2A
TP
6V
1F
AT
P6
V1
G1
AT
P6
V1
G2
AT
P6
V1
G3
AT
P6
V1
HC
OX
10
CO
X1
1C
OX
15
CO
X1
7C
OX
4I1
CO
X4
I2C
OX
5A
CO
X5
BC
OX
6A
1C
OX
6A
2C
OX
6B
1C
OX
6B
2C
OX
6C
CO
X7
A1
CO
X7
A2
CO
X7
A2
LC
OX
7B
CO
X7
B2
CO
X7
CC
OX
8A
CY
C1
ND
UF
A1
Oxid
ative
_S
tre
ss_
an
d_
An
tio
xid
an
t_D
efe
nse
84
SG
SS
GS
TZ
1G
TF
2I
KR
T1
LP
OM
BL
2M
GS
T3
MP
OM
PV
17
MS
RA
MT
3M
TL
5N
CF
1N
CF
2N
ME
5N
OS
2A
NO
X5
NU
DT
1O
XR
1O
XS
R1
PD
LIM
1P
IP3
-EP
NK
PP
RD
X1
PR
DX
2P
RD
X3
PR
DX
4P
RD
X5
PR
DX
6P
RE
X1
PR
G3
p5
3_
Sig
na
ling
_P
ath
wa
y1
13
SC
IAO
1C
OP
EB
CR
AD
DC
YR
61
DA
PK
1D
AX
XE
2F
1E
2F
3E
I24
ES
R1
FA
DD
FA
F1
FO
XO
3A
FR
AP
1G
AD
D4
5A
GA
KG
AS
1G
ML
GT
SE
1H
DA
C1
HK
2IF
NB
1IG
F1
RIL
6JU
NK
RA
S2
LR
DD
MC
L1
MD
M2
MD
M4
MS
H2
Pa
sse
rin
i_P
rolif
era
tio
n6
5m
sig
db
IL8
RB
US
P8
SP
OC
K1
CU
L4
AIL
1A
FG
F2
CD
C2
5C
CX
CL
10
MA
PR
E1
FL
T1
UB
E2
V2
PM
P2
2P
RK
RA
MA
D1
L1
CD
KN
2C
CD
KN
1B
PL
GIL
12
RB
1C
DK
N1
CH
BE
GF
PC
NA
KL
F4
VE
GF
CN
UL
LT
GF
AP
BE
F1
PG
FP
TK
2B
EM
P1
E4
F1
CD
KN
1A
Ph
osp
ha
tase
s1
05
rese
nt_
stu
dP
TP
N1
2P
TP
N1
3P
TP
N1
4P
TP
N1
8P
TP
N2
0B
PT
PN
21
PT
PN
22
PT
PN
23
DU
SP
1D
US
P2
DU
SP
4D
US
P5
DU
SP
6D
US
P7
DU
SP
8D
US
P9
DU
SP
10
DU
SP
16
ST
YX
L1
DU
SP
3D
US
P1
1D
US
P1
2D
US
P1
3D
US
P1
4D
US
P1
5D
US
P1
8D
US
P1
9D
US
P2
1D
US
P2
2D
US
P2
3D
US
P2
6
PI3
K-A
KT
_S
ign
alin
g_
Pa
thw
ay
11
3S
FO
SF
OX
O1
AF
OX
O3
AF
RA
P1
FZ
D1
GH
RG
JA
1G
NB
1G
RB
10
GR
B2
GS
K3
BH
RA
SH
SP
B1
HS
PC
AH
SP
CB
IGF
1IG
F1
RIL
KIN
PP
5D
INP
PL
1IR
AK
1IR
S1
ITG
B1
JU
NL
BP
LE
F1
LY
96
MA
P2
K1
MA
PK
1M
AP
K1
4M
AP
K3
PP
AR
_sig
na
ling
_p
ath
wa
y_
KE
GG
67
KF
AB
P4
FA
BP
5F
AB
P6
FA
BP
7F
AD
S2
GK
GK
2H
MG
CS
1H
SD
17
B4
ILK
LP
LM
E1
MM
P1
NR
1H
3O
LR
1P
CK
1P
CK
2P
DP
K1
PL
INP
LT
PP
PA
RA
PP
AR
DP
PA
RG
RX
RA
RX
RB
RX
RG
SC
DS
CP
2S
LC
27
A1
SL
C2
7A
2S
LC
27
A4
Pro
life
ratio
n_
Sig
na
ture
51
Wh
itfie
ld e
t a
CC
NE
1C
CN
FC
DC
20
DD
X1
1E
2F
3M
KI6
7P
KM
YT
1P
LK
1T
IMP
1C
DC
25
CC
EN
PF
MA
PK
13
EX
OS
C9
MY
BT
P5
3C
DH
3E
GF
RE
RB
B2
CC
NE
2K
RT
5
Pro
tea
so
me
_K
EG
G3
1K
Re
cu
rre
nce
_S
co
re1
6
Re
gu
latio
n_
of_
actin
_cyto
ske
leto
n_
KE
GG
20
1K
CH
RM
2C
HR
M3
CH
RM
4C
HR
M5
CR
KC
RK
LC
SK
CY
FIP
1C
YF
IP2
DIA
PH
1D
IAP
H2
DIA
PH
3D
OC
K1
EG
FE
GF
RF
2F
2R
FG
D1
FG
D3
FG
F1
FG
F1
0F
GF
11
FG
F1
2F
GF
13
FG
F1
4F
GF
16
FG
F1
7F
GF
18
FG
F1
9F
GF
2F
GF
20
Re
gu
latio
n_
of_
au
top
ha
gy_
KE
GG
28
K
Rib
ofla
vin
_m
eta
bo
lism
_K
EG
G1
6K
Rib
oso
me
_K
EG
G8
6K
RP
L3
2R
PL
34
RP
L3
5R
PL
35
AR
PL
36
RP
L3
6A
RP
L3
6A
LR
PL
37
RP
L3
7A
RP
L3
8R
PL
39
RP
L4
RP
L4
1R
PL
5R
PL
6R
PL
7R
PL
7A
RP
L8
RP
L9
RP
LP
0R
PL
P1
RP
S1
0R
PS
11
RP
S1
2R
PS
13
RP
S1
4R
PS
15
RP
S1
5A
RP
S1
6R
PS
17
RP
S1
8
Ro
tte
rda
m_
sig
na
ture
68
Ja
nse
n e
t a
lO
RC
3L
SA
T1
GT
SE
1T
AC
C2
KP
NA
2 /
// L
AP
2A
2M
AP
4B
ICD
1F
LJ2
54
76
EIF
4E
BP
3 /E
TV
2L
ST
1F
UT
3M
AG
CO
L2
A1
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53
87
9GO
LP
H2
SU
PT
16
HR
FX
DC
2Z
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HC
8U
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AT
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66
CL
N8
PO
LQ
NC
AP
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74
8G
AB
RQ
GF
OD
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14
Sh
ep
ard
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rolif
era
tio
n2
32
msig
db
CY
R6
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OS
MR
MS
4A
1E
MP
3C
HR
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US
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INS
L4
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RG
TC
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PD
CD
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IPE
MP
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KS
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Y
Sh
ep
ard
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eg
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g_
of_
ce
ll_p
rolif
era
tio
n1
16
msig
db
AD
RA
1A
BT
G1
CD
KN
1B
IL8
CD
KN
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AP
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1C
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10
CG
RE
F1
LD
OC
1G
NR
H1
PT
HL
HIL
6P
PM
1D
QS
CN
6D
LG
5P
RK
RB
TG
2S
10
0A
11
BA
P1
FR
KB
TG
33
97
83
TO
B1
GM
LF
AB
P7
TG
FB
1I1
CD
KN
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ST
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ET
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I1Z
RA
NB
1
Sig
na
l_T
ran
sd
uctio
n_
in_
Ca
nce
r9
8S
FO
SF
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FO
XA
2G
AD
D4
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AH
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HM
OX
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PA
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HS
PB
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CA
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IGF
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TA
MC
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NF
KB
1N
FK
BIA
NO
S2
A
Sig
na
l_T
ran
sd
uctio
n_
Pa
thw
ay_
Fin
de
r1
14
SC
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L1
2C
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GF
RE
GR
1E
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SN
FL
J1
25
41
FN
1F
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FO
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EB
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PC
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IGF
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4IK
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BIL
1A
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IL2
RA
IL4
IL4
RIL
8
Sp
hin
go
lipid
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eta
bo
lism
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EG
G3
7K
SP
HK
1S
PT
LC
1S
PT
LC
2T
ME
M2
3U
GC
GU
GT
8
Str
ess_
&_
To
xic
ity_
Pa
thw
ay_
Fin
de
r9
6S
FM
O1
FM
O5
GA
DD
45
AG
AD
D4
5B
GD
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1G
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GS
TM
3H
MO
X1
HM
OX
2H
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AH
SP
A1
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PA
4H
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HS
PA
6H
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HS
PA
9B
HS
PB
1H
SP
CA
HS
PC
BH
SP
D1
HS
PE
1H
SP
H1
IGF
BP
6IL
18
IL1
AIL
1B
IL6
LT
A
Str
ess_
Re
sp
on
se
_to
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ellu
lar_
Da
ma
ge
96
SD
NA
JA
3D
NA
JA
4D
NA
JB
1D
NA
JB
11
DN
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2D
NA
JB
4D
NA
JB
5D
NA
JB
6D
NA
JB
9D
NA
JC
4D
NA
JC
5D
NA
JC
6D
NA
JC
7D
NA
JC
8D
NA
JC
9D
NA
JD
1E
PH
X2
FM
O1
FM
O4
FM
O5
GP
X1
GP
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GR
P5
8G
SR
GS
TM
3G
ST
O1
GS
TP
1G
ST
T1
HM
OX
1H
MO
X2
HO
P
T_
ce
ll_re
ce
pto
r_sig
na
ling
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ath
wa
y_
KE
GG
92
KIK
BK
GIL
10
IL2
IL4
IL5
ITK
JU
NK
RA
SL
AT
LC
KL
CP
2M
AL
T1
MA
P3
K1
4M
AP
3K
8N
CK
1N
CK
2N
FA
T5
NF
AT
C1
NF
AT
C2
NF
AT
C3
NF
AT
C4
NF
KB
1N
FK
B2
NF
KB
IAN
FK
BIB
NF
KB
IEN
RA
SP
AK
1P
AK
2P
AK
3P
AK
4
T-c
ell_
an
d_
B-c
ell_
Activa
tio
n6
6S
CS
F2
CX
3C
L1
CX
CR
3C
XC
R4
GA
LN
AC
4SG
LM
NH
DA
C4
HD
AC
5H
DA
C7
AH
DA
C9
HL
A-D
RA
ICO
SL
IFN
A2
IFN
B1
IFN
GIF
NG
R1
IFN
GR
2IF
NK
IGB
P1
IL1
0IL
11
IL1
2A
IL1
2B
IL1
2R
B1
IL1
2R
B2
IL1
3IL
18
IL1
8R
1IL
2IL
21
RIL
27
TG
F-b
eta
_sig
na
ling
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ath
wa
y1
16
SC
OL
1A
1C
OL
1A
2C
OL
3A
1C
OM
PC
RE
BB
PC
ST
3C
UL
1D
CN
DL
X2
E2
F4
E2
F5
EN
GE
P3
00
EV
I1F
KB
P1
BF
OS
FS
TG
DF
1G
DF
10
GD
F1
1G
DF
15
GD
F2
GD
F3
GD
F5
GD
F6
GD
F7
GD
F8
GD
F9
GR
EM
1G
SC
HIP
K2
Th
1-T
h2
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36
2S
HA
VC
R2
ICO
SIF
NG
IGS
F6
IL1
0IL
12
BIL
12
RB
2IL
13
IL1
3R
A1
IL1
3R
A2
IL1
5IL
17
FIL
18
IL1
8B
PIL
18
R1
IL1
R1
IL1
R2
IL2
IL2
7IL
2R
AIL
4IL
4R
IL5
IL6
IL6
RIL
7IL
9IN
HA
INH
BA
IRF
1IR
F4
Tig
ht_
jun
ctio
n_
KE
GG
11
4K
CL
DN
8C
LD
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CR
B3
CS
DA
CS
NK
2A
1C
SN
K2
A2
CS
NK
2B
CT
NN
A1
CT
NN
A2
CT
NN
A3
CT
NN
B1
CT
TN
EP
B4
1E
PB
41
L1
EP
B4
1L
2E
PB
41
L3
EX
OC
3E
XO
C4
F1
1R
FK
SG
30
GN
AI1
GN
AI2
GN
AI3
HC
LS
1H
RA
SIN
AD
LJA
M2
JA
M3
KR
AS
LL
GL
1L
LG
L2
TN
F_
L&
R2
8S
To
ll-lik
e_
rece
pto
r_sig
na
ling
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ath
wa
y_
KE
GG
90
KIF
NA
R1
IFN
AR
2IF
NB
1IK
BK
BIK
BK
EIK
BK
GIL
12
AIL
12
BIL
1B
IL6
IL8
IRA
K1
IRA
K4
IRF
3JU
NL
BP
LY
96
MA
P2
K3
MA
P2
K4
MA
P2
K6
MA
P3
K7
MA
P3
K7
IP1M
AP
3K
7IP
2MA
PK
10
MA
PK
11
MA
PK
12
MA
PK
13
MA
PK
14
MA
PK
8M
AP
K9
MY
D8
8
To
xic
olo
gy_
&_
Dru
g_
Re
sis
tan
ce
73
SC
CL
21
CC
L3
CC
L4
CC
NC
CC
ND
1C
CN
E1
CC
NG
1C
CT
2C
CT
3C
CT
4C
CT
5C
CT
7C
CT
8C
DK
2C
DK
4C
DK
N1
AC
DK
N1
BC
DK
N2
AC
DK
N2
DC
ES
1C
HE
K2
CH
ST
1C
HS
T1
0C
HS
T2
CH
ST
3C
HS
T4
CH
ST
5C
HS
T6
CH
ST
7C
HS
T8
CL
U
TS
P1
_p
ath
wa
y7
S
Tu
mo
r_M
eta
sta
sis
59
SB
AI1
GN
RH
2M
ET
AP
2R
B1
FG
FR
4IL
8R
BM
DM
2M
YB
FL
T4
CD
K4
ITG
A7
PC
OL
N3
ET
V4
S1
00
A4
CX
CL
12
HP
SE
GN
RH
1G
ZM
AN
ME
4N
F2
CX
CR
4M
MP
13
AP
CN
R4
A3
CS
T7
MM
P1
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TA
TIP
2C
TN
NA
1
Tu
mo
r_N
ecro
sis
_F
acto
r7
0S
MA
P3
K7
MA
PK
8N
FK
B1
NF
KB
IAN
GF
RP
AK
1P
AK
2P
AR
P1
PG
LY
RP
1P
RK
DC
RB
1S
PT
AN
1T
AN
KT
NF
TN
FA
IP3
TN
FR
SF
10
TN
FR
SF
10
TN
FR
SF
10
TN
FR
SF
10
TN
FR
SF
11
TN
FR
SF
11
TN
FR
SF
12
TN
FR
SF
13
TN
FR
SF
13
TN
FR
SF
14
TN
FR
SF
17
TN
FR
SF
18
TN
FR
SF
19
TN
FR
SF
19
TN
FR
SF
1A
TN
FR
SF
1B
Tu
mo
r_S
up
pre
sso
r2
6m
sig
db
Tyro
sin
e_
me
tab
olis
m_
KE
GG
55
KL
CM
T2
MA
OA
MA
OB
ME
TT
L2
BM
ET
TL
6M
IFM
YS
T3
MY
ST
4N
AT
5P
NM
TP
NP
LA
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PR
MT
2P
RM
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PR
MT
5P
RM
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PR
MT
7P
RM
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SH
3G
LB
1T
AT
TH
TP
OT
YR
TY
RP
1
Un
de
rhill
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rolif
era
tio
n1
9n
de
rhill
et
al.
VE
GF
_sig
na
ling
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ath
wa
y_
KE
GG
69
KP
IK3
CD
PIK
3C
GP
IK3
R1
PIK
3R
2P
IK3
R3
PIK
3R
5P
LA
2G
10
PL
A2
G1
2A
PL
A2
G1
2B
PL
A2
G1
BP
LA
2G
2A
PL
A2
G2
DP
LA
2G
2E
PL
A2
G2
FP
LA
2G
3P
LA
2G
4A
PL
A2
G5
PL
A2
G6
PL
CG
1P
LC
G2
PP
P3
CA
PP
P3
CB
PP
P3
CC
PP
P3
R1
PR
KC
AP
RK
CB
1P
RK
CG
PT
K2
PX
NR
AC
1R
AC
2
vV
_7
0g
en
e_
Sig
na
ture
61
an
't V
ee
r e
t aL
GP
2L
OC
64
30
08M
CM
6M
EL
KM
MP
9M
S4
A7
MT
DH
NM
UN
US
AP
1O
RC
6L
OX
CT
1P
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APE
CI
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1P
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C2
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C1
QS
CN
6L
1R
AB
6A
RF
C4
RP
5-8
60
F1
RT
N4
RL
1R
UN
DC
1S
CU
BE
2S
LC
2A
14
ST
K3
2B
TG
FB
3T
SP
YL
5U
CH
L5
WIS
P1
ZN
F5
33
Wn
t_S
ign
alin
g_
Pa
thw
ay
17
5S
CT
NN
BIP
1C
UL
1C
XX
C4
DA
AM
1D
AA
M2
DIX
DC
1D
KK
1D
KK
2D
KK
3D
KK
4D
VL
1D
VL
2D
VL
3E
P3
00
FB
XW
11
FB
XW
2F
GF
4F
OS
L1
FO
XN
1F
RA
T1
FR
AT
2F
RZ
BF
SH
BF
ZD
1F
ZD
10
FZ
D2
FZ
D3
FZ
D4
FZ
D5
FZ
D6
FZ
D7
NO
TE:
Num
ber
ofge
nes
pres
ent
inea
chge
nese
tsan
dso
urce
are
indi
cate
d(m
sigd
b=M
olec
ular
Sign
atur
esD
atab
ase
http
://w
ww
.bro
ad.m
it.ed
u/gs
ea/m
sigd
b/in
dex.
jsp,
K=K
EGG
,S=w
ww
.supe
rarr
ay.c
om,
Rose
nwal
det
al.
Can
cerC
ell.
2003
Feb;
3(2)
:185
-97,
Potti
etal
.N
atM
ed.
2006
Nov
;12(
11):1
294-
300,
Whi
tfiel
d et
al.
Mol
Bio
l Cel
l. 20
02 Ju
n;13
(6):1
977-
2000
, Pai
k et
al.
N E
ngl J
Med
. 200
4 D
ec 3
0;35
1(27
):281
7-26
, K
lijn
et a
l. J
Clin
O
ncol
. 200
6 A
pr 1
0;24
(11)
:166
5-71
, Sh
epar
d et
al.
Pro
c N
atl A
cad
Sci U
S A
. 200
5 Se
p 13
;102
(37)
:131
94-9
, U
nder
hill
et a
l. B
lood
. 200
3 M
ay 1
5;10
1(10
):401
3-21
, van
't Ve
er e
t al.
Nat
ure.
200
2 Ja
n 31
;415
(687
1):5
30-6
.
Pa
ge
3
GE
NE
SE
TS
N
. G
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urc
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pb
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R1
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WA
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AS
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S1
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dro
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n_
Sig
na
ling
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nd
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rosta
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nce
r9
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PA
P2
BP
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NR
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AR
NF
14
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20
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1
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ne
sis
11
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MP
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PP
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PR
1N
RP
1N
RP
2N
UD
T6
PD
GF
AP
DG
FB
PE
CA
M1
PF
4P
GF
PL
AU
PL
GP
LX
DC
1P
RO
K2
PT
EN
PT
GS
1P
TG
S2
PT
NR
NA
SE
4S
ER
PIN
F1
SH
2D
2A
SP
HK
1S
TA
B1
ST
AB
2T
EK
An
tig
en
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roce
ssin
g_
an
d_
pre
se
nta
tio
n_
KE
GG
73
NF
YA
KN
FY
BN
FY
CP
DIA
3P
SM
E1
PS
ME
2R
FX
5R
FX
AP
TA
P1
TA
P2
TA
PB
P
Ap
op
tosis
16
3C
HP
SC
HU
KC
IDE
AC
IDE
BC
RA
DD
CS
F2
RB
CY
CS
DA
PK
1D
AP
K2
DF
FA
DF
FB
EN
DO
GF
AD
DF
AS
FA
SL
GG
AD
D4
5A
GD
NF
HR
KIG
F1
RIK
BK
BIK
BK
GIL
1A
IL1
BIL
1R
1IL
1R
AP
IL3
IL3
RA
IRA
K1
IRA
K2
IRA
K4
LT
A
Bre
ast_
Ca
nce
r_E
str
og
en
_S
ign
alin
g1
01
HS
PB
1m
sig
db
HM
GB
1S
CG
B2
A1
MU
C1
TN
FA
IP2
VE
GF
TF
F1
MK
I67
CD
KN
2A
TN
FR
SF
6T
IEA
ZG
P1
ES
R1
EG
FR
ES
R2
JU
NR
PL
13
AS
10
0A
2K
LF
5B
PA
G1
SE
RP
INA
3N
GF
BK
RT
HB
6K
ITS
ER
PIN
B5
PG
RA
RG
AP
DT
HB
S1
CD
H1
TH
BS
4
Ca
lciu
m_
sig
na
ling
_p
ath
wa
y_
KE
GG
17
1E
RB
B2
KE
RB
B3
ER
BB
4F
2R
GN
A1
4G
NA
LG
NA
QG
NA
SG
RIN
1G
RIN
2A
GR
IN2
CG
RIN
2D
GR
M1
GR
M5
GR
PR
HR
H1
HR
H2
HT
R2
AH
TR
2B
HT
R2
CH
TR
4H
TR
5A
HT
R6
HT
R7
ITP
KA
ITP
KB
ITP
R1
ITP
R2
ITP
R3
LH
CG
RM
LC
K
Ce
ll_a
dh
esio
n_
mo
lecu
les_
(CA
Ms)_
KE
GG
12
5H
LA
-DR
AK
HL
A-D
RB
1H
LA
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B4
HL
A-E
HL
A-F
HL
A-G
ICA
M1
ICA
M2
ICA
M3
ICO
SIC
OS
LG
IGS
F4
IGS
F4
BIT
GA
4IT
GA
6IT
GA
8IT
GA
9IT
GA
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GA
MIT
GA
VIT
GB
1IT
GB
2IT
GB
7IT
GB
8JA
M2
JA
M3
L1
CA
MM
AD
CA
M1
MA
GM
PZ
MP
ZL
1
Ce
ll_C
ycle
89
CD
C7
SS
KP
1A
MC
M6
CD
K5
RA
P1B
CL
2C
DC
34
CD
K6
GT
SE
1C
CN
T1
MA
D1
L1
CD
KN
2B
CD
K5
R2
OR
C6
LC
UL
2C
DK
8B
UB
1C
CN
HE
2F
1T
FD
P1
DD
X1
1C
CN
G2
AT
RO
RC
2L
CU
L1
CD
C2
5C
AN
AP
C5
RB
1
Ce
ll_P
rolif
era
tio
n7
2B
UB
1B
Ro
se
nw
ald
et
al.
BU
B1
EV
I5B
UB
3P
CN
AIL
6M
NA
T1
MT
CP
1K
HD
RB
S1
TF
DP
1
Ch
em
okin
e_
Lig
an
d_
Re
ce
pto
r1
69
CC
L8
S
CC
L9
/10
C
CR
1C
CR
10
CC
R2
CC
R3
CC
R4
CC
R5
CC
R6
CC
R7
CC
R8
CC
R9
CC
RL
1C
CR
L2
CK
LF
CK
LF
SF
1C
KL
FS
F2
CK
LF
SF
3C
KL
FS
F4
CK
LF
SF
5C
KL
FS
F6
CK
LF
SF
7C
KL
FS
F8
CM
KL
R1
CM
KO
R1
CS
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3C
L1
CX
3C
L1
C
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CR
1C
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L1
C
XC
L1
0
Co
lore
cta
l_ca
nce
r_K
EG
G7
8R
AC
1K
RA
C2
RA
C3
RA
F1
RA
LG
DS
SM
AD
2S
MA
D3
SO
S1
SO
S2
TC
F7
TG
FB
1T
GF
B2
TG
FB
3T
GF
BR
1T
GF
BR
2T
P5
3
Co
mm
on
_C
yto
kin
e1
08
IL2
1S
IL2
2IL
24
IL2
6IL
3IL
4IL
5IL
6IL
7IL
8IL
9IN
HA
INH
BA
INH
BB
LA
SS
1L
EF
TY
2L
TA
LT
BN
OD
AL
PD
GF
AP
DG
FB
PT
NS
LU
RP
1S
PP
1T
GF
AT
GF
B1
TG
FB
2T
GF
B3
TH
PO
TN
FT
NF
RS
F1
1
Co
mp
lem
en
t_a
nd
_co
ag
ula
tio
n_
ca
sca
de
s_
KE
GG
65
TF
PI
KT
HB
DV
WF
DN
A_
Da
ma
ge
_S
ign
alin
g_
Pa
thw
ay
10
7P
CN
AS
PD
CD
8P
MS
1P
MS
2P
MS
2L
4P
MS
2L
9P
NK
PP
PP
1R
15
AP
RK
DC
RA
D1
RA
D1
7R
AD
18
RA
D2
1R
AD
23
AR
AD
23
BR
AD
50
RA
D5
1R
AD
51
CR
AD
51
L1
RA
D5
1L
3R
AD
52
RA
D5
4L
RA
D9
AR
BB
P8
RE
V1
LR
PA
1R
PA
3S
EM
A4
AS
ES
N1
SM
C1
L1
SU
MO
1
EC
M_
extr
ace
llula
r1
56
EC
M1
SE
FE
MP
1E
FE
MP
2E
LN
EM
ILIN
1E
MIL
IN2
ES
AM
FA
NK
1F
BL
N1
FB
LN
2F
BL
N5
FB
N1
FB
N2
FB
N3
FC
N1
FC
N2
FC
N3
FL
RT
1F
LR
T2
FL
RT
3F
N1
FS
D1
HA
PL
N1
HA
PL
N2
HA
PL
N3
HA
PL
N4
HS
PG
2IB
SP
IMP
G1
IMP
G2
LA
MA
1
EC
M_
inh
ibito
rs&
oth
er_
en
zym
es
82
SE
RP
ING
1S
SE
RP
INH
1S
ER
PIN
I1S
ER
PIN
I2S
PA
M1
SP
G2
0S
PG
21
SP
G3
AS
PG
7T
GM
1T
GM
2T
GM
3T
GM
4T
GM
5T
GM
6T
GM
7T
IMP
1T
IMP
2T
IMP
3T
IMP
4
EC
M_
me
mb
ran
e_
ce
ll-ce
ll_a
dh
esio
n1
38
PC
DH
18
SP
CD
H1
9P
CD
H2
0P
CD
H2
1P
CD
H7
PC
DH
8P
CD
H9
PC
DH
A1
PC
DH
A1
0P
CD
HA
11
PC
DH
A1
2P
CD
HA
13
PC
DH
A2
PC
DH
A3
PC
DH
A4
PC
DH
A5
PC
DH
A6
PC
DH
A7
PC
DH
A8
PC
DH
A9
PC
DH
AC
1P
CD
HA
C2
PC
DH
B1
PC
DH
B1
0P
CD
HB
11
PC
DH
B1
2P
CD
HB
13
PC
DH
B1
4P
CD
HB
15
PC
DH
B1
6P
CD
HB
17
EC
M_
me
mb
ran
e_
ce
ll-m
atr
ix_
ad
he
sio
n1
61
PIG
QS
PL
XD
C1
PL
XD
C2
PL
XN
A1
PL
XN
A2
PL
XN
A3
PL
XN
A4
AP
LX
NA
4B
PL
XN
B1
PL
XN
B2
PL
XN
B3
PL
XN
C1
PL
XN
D1
PU
NC
SD
C2
SD
C4
SE
MA
3A
SE
MA
3B
SE
MA
3C
SE
MA
3D
SE
MA
3E
SE
MA
3F
SE
MA
3G
SE
MA
4A
SE
MA
4B
SE
MA
4C
SE
MA
4D
SE
MA
4F
SE
MA
4G
SE
MA
5A
SE
MA
5B
EC
M_
pro
tea
se
s2
04
CP
MS
CP
N1
CP
N2
CP
XM
CP
XM
2C
TS
BC
TS
CC
TS
DC
TS
EC
TS
FC
TS
GC
TS
HC
TS
KC
TS
LC
TS
L2
CT
SL
L3
CT
SO
CT
SS
CT
SW
CT
SZ
DA
B1
DK
FZ
P5
86
DP
P1
0D
PP
4D
PP
6D
PP
9E
LA
1E
LA
2E
LA
2A
EL
A2
BE
LA
3A
EC
M-r
ece
pto
r_in
tera
ctio
n_
KE
GG
85
LA
MC
1K
LA
MC
2L
AM
C3
LO
C1
31
87
3RE
LN
SD
C1
SD
C2
SD
C3
SD
C4
SP
P1
SV
2A
SV
2B
SV
2C
TH
BS
1T
HB
S2
TH
BS
3T
HB
S4
TN
CT
NN
TN
RT
NX
BV
TN
VW
F
EG
F_
PD
GF
_S
ign
alin
g_
Pa
thw
ay
96
MM
P7
SN
FA
TC
3N
FK
B1
NR
AS
PD
GF
AP
DG
FB
PD
GF
RA
PD
GF
RB
PD
PK
1P
IK3
CA
PIK
3C
BP
IK3
R1
PIK
3R
2P
LC
G1
PL
CG
2P
PP
2C
AP
RK
CA
PT
EN
PT
PN
11
RA
F1
RA
P1
AR
AS
A1
RP
S6
KA
5R
PS
6K
B1
RP
S6
KB
2S
FN
SH
C1
SR
CS
TA
T1
ST
AT
3S
TA
T5
A
En
do
the
lial_
Ce
ll_B
iolo
gy
12
1IL
1B
SIL
3IL
6IL
7IL
8IT
GA
5IT
GA
VIT
GB
1IT
GB
3K
DR
KIT
KL
K3
LT
B4
RM
AS
1M
MP
1M
MP
14
MM
P2
MM
P9
NO
S2
AN
OS
3N
PP
BN
PR
1O
CL
NP
DG
FR
AP
DG
FR
BP
EC
AM
1P
F4
PG
FP
LA
TP
LA
UP
LG
Fo
ca
l_a
dh
esio
n_
KE
GG
19
3G
RB
2K
GR
LF
1G
SK
3B
HG
FH
RA
SIB
SP
IGF
1IG
F1
RIL
KIT
GA
10
ITG
A1
1IT
GA
2IT
GA
2B
ITG
A3
ITG
A4
ITG
A5
ITG
A6
ITG
A7
ITG
A8
ITG
A9
ITG
AV
ITG
B1
ITG
B3
ITG
B4
ITG
B5
ITG
B6
ITG
B7
ITG
B8
JU
NK
DR
LA
MA
1
Fo
late
_b
iosyn
the
sis
_K
EG
G3
7K
G_
Pro
tein
-Co
up
led
_R
ece
pto
r9
6M
C2
RS
MC
3R
MC
4R
MC
5R
MT
NR
1A
MT
NR
1B
OP
RD
1O
PR
K1
OP
RL
1O
PR
M1
OX
TP
2R
X4
P2
RY
1P
2R
Y1
1P
2R
Y1
2P
2R
Y2
P2
RY
4P
2R
Y6
PT
GD
RP
TG
ER
2P
TG
ER
3P
TG
ER
4P
TG
FR
PT
HR
2R
GR
SS
TR
1S
ST
R2
SS
TR
3S
ST
R4
SS
TR
5T
RH
R
G_
Pro
tein
-Co
up
led
_R
ece
pto
r_II
97
MA
P3
K5
SM
AP
K1
0M
KN
K2
MM
DN
MU
2R
NP
Y1
RN
TN
1N
TS
R2
PT
K2
BR
AI3
RA
MP
1R
AM
P2
RA
MP
3R
GS
10
RG
S1
1R
GS
12
RG
S1
3R
GS
16
RG
S2
RG
S2
0R
GS
3R
GS
4R
GS
7R
GS
9S
RE
B3
TA
S2
R1
TA
S2
R1
3T
AS
2R
14
TA
S2
R7
TA
S2
R8
TA
S2
R9
Ga
p_
jun
ctio
n_
KE
GG
95
PD
GF
RB
KP
LC
B1
PL
CB
2P
LC
B3
PL
CB
4P
RK
AC
AP
RK
AC
BP
RK
AC
GP
RK
CA
PR
KC
B1
PR
KC
GP
RK
G1
PR
KG
2P
RK
XP
RK
YR
AF
1S
OS
1S
OS
2S
RC
TJP
1T
UB
A1
TU
BA
2T
UB
A3
TU
BA
4T
UB
A8
TU
BB
TU
BB
1T
UB
B2
BT
UB
B2
CT
UB
B3
TU
BB
4
Ge
ne
s_
co
nstitu
tin
g_
the
_P
I3_
kin
ase
_p
red
icto
r1
32
LM
NB
2P
ott
i e
t a
l.M
AC
30
MA
D2
L1
MC
M1
0M
CM
2M
CM
3M
CM
4M
CM
5M
CM
6M
CM
7M
GC
10
99
3M
GC
13
09
6M
GC
20
41
9M
GC
23
28
0M
GC
35
52
1M
GC
45
04
MG
C4
69
2M
SH
2M
SH
6M
TH
FD
1M
YB
NA
SP
NO
L5
AP
CN
AP
DX
PP
EX
5P
fs2
PO
LA
2P
OL
D1
PO
LD
3P
OL
R1
B
Ge
no
me
_S
tab
ility
_D
NA
_R
ep
air
11
3P
MS
2L
9S
PN
KP
PO
LD
3P
OL
LP
RK
DC
RA
D1
8R
AD
21
RA
D2
3A
RA
D2
3B
RA
D5
0R
AD
51
RA
D5
1C
RA
D5
1L
1R
AD
51
L3
RA
D5
2R
AD
54
BR
AD
54
LR
FC
1R
PA
1R
PA
3S
LK
SM
UG
1T
DG
TE
P1
TE
RF
1T
ER
F2
TE
RF
2IP
TE
RT
TIN
F2
TN
KS
TN
KS
1B
P1
G-P
rote
in_
Co
up
led
_R
ece
pto
rs_
Sig
na
ling
99
MM
P9
SM
YC
NO
S2
AN
PP
AN
PY
OP
RD
1O
PR
K1
PD
PK
1P
IK3
CG
PO
LY
DO
MP
RIC
28
5P
RK
CA
PR
LP
TG
DR
PT
GE
R1
PT
GS
2R
GS
2R
HO
SC
YA
2S
CY
A4
SE
RP
INE
1S
SI-
1S
SI-
3T
NF
TS
HR
UC
P1
VC
AM
1V
EG
FY
WH
AZ
ßA
GT
R2
ßA
KT
1
G-P
rote
ins_
&_
Sig
na
ling
_M
ole
cu
les
96
PIK
3C
BS
PL
CB
1P
LC
B2
PL
CB
4P
LD
1P
LD
2P
LD
3P
RK
AC
AP
RK
AC
BP
RK
AR
1A
PR
KA
R1
BP
RK
AR
2B
PR
KC
AP
RK
CB
1P
RK
CE
PR
KC
GP
RK
CM
PT
K2
PT
K2
BP
XN
PY
GB
PY
GL
PY
GM
RA
F1
RA
P1
AR
AS
A1
RD
XR
OC
K1
SH
C1
SO
S1
SR
C
Gro
wth
_F
acto
r8
4M
DK
SN
DP
NG
FB
NO
DA
LN
RG
1N
RG
2N
RG
3N
RT
NN
TF
3O
KL
38
PD
GF
CP
GF
PS
PN
PT
NS
LC
O1
A2
SP
P1
TD
GF
1T
GF
B1
TH
PO
TN
NT
1V
EG
FV
EG
FC
He
dg
eh
og
_sig
na
ling
_p
ath
wa
y_
KE
GG
55
K
Hyp
oxia
_S
ign
alin
g_
Pa
thw
ay
48
S
IL1
8_
pa
thw
ay
6m
sig
db
IL3
_P
ath
wa
y1
5m
sig
db
IL6
PA
TH
WA
Y2
3m
sig
db
IL7
PA
TH
WA
Y1
8m
sig
db
Infla
mm
ato
ry_
Cyto
kin
es_
&_
Re
ce
pto
rs9
3IL
12
RB
1S
IL1
2R
B2
IL1
3IL
13
RA
1IL
13
RA
2IL
15
IL1
5R
AIL
16
IL1
7IL
17
CIL
17
RIL
18
IL1
8R
1IL
1A
IL1
BIL
1R
1IL
1R
2IL
1R
NIL
2IL
20
IL2
1IL
22
IL2
RA
IL2
RB
IL2
RG
IL3
IL4
IL5
IL5
RA
IL6
IL6
R
Ino
sito
l_p
ho
sp
ha
te_
me
tab
olis
m_
KE
GG
51
K
Insu
lin_
Sig
na
ling
_P
ath
wa
y1
71
GR
B2
SG
SK
3A
GS
K3
BG
YS
1G
YS
2H
K2
HR
AS
IGF
1R
IGF
2IG
FB
P1
IKB
KB
INP
P5
DIN
SIN
SL
3IN
SR
IRS
1IR
S2
IRS
4K
IAA
13
03
KR
AS
LIP
EM
AP
2K
1M
AP
2K
2M
AP
K1
MA
PK
10
MA
PK
3M
AP
K8
MA
PK
9M
KN
K1
MK
NK
2N
RA
S
Inte
rfe
ron
84
IL6
RS
IL7
RIL
9R
IRF
1IR
F2
IRF
2B
P1
IRF
2B
P2
IRF
3IR
F4
IRF
5IR
F6
IRF
7IR
F8
IRG
ML
EP
RM
PL
MX
1O
AS
1P
SM
E1
PY
HIN
1S
P1
10
TT
N
Inte
rfe
ron
_a
,b_
Re
sp
on
se
96
MA
P2
K1
SM
ET
MN
TM
X1
MX
2M
YC
MY
D8
8N
MI
NR
G1
OA
S1
OA
S2
OA
SL
PL
A2
G1
BP
ML
PR
KC
ZP
RK
RA
PR
KR
IP1
PS
ME
2P
TT
G1
RC
BT
B1
SA
MS
N1
SH
2D
1A
SL
C1
A2
SO
CS
1S
OC
S3
ST
AT
1S
TA
T2
TA
P1
TN
FS
F1
0T
NF
SF
7T
RIM
22
Inte
rle
ukin
s_
an
d_
Re
ce
pto
rs7
1IL
7S
IL7
RIL
8IL
8R
AIL
8R
BIL
9IL
9R
ßF
IL1
ßIL
1R
1
Inva
siv
en
ess_
Ge
ne
_S
ign
atu
re1
89
GA
BA
RA
PL
Liu
et
al.
GA
BA
RA
PLH
SP
A2
AR
PC
5C
SN
K2
A1
PR
EP
LA
TP
13
A3
TU
BB
C1
OR
F1
21
CD
59
DN
AJC
13
PD
E8
AW
EE
1A
IM1
DC
UN
1D
4S
KIV
2L
2C
5O
RF
21
CE
P3
50
CA
SP
8C
G0
18
GA
PD
HS
FP
QE
RB
B4
LA
RS
NA
T1
0D
HR
S4
FA
M5
3C
NO
L8
BD
H2
C1
6O
RF
33
C1
7O
RF
71
JA
K_
ST
AT
_S
ign
alin
g_
Pa
thw
ay
17
9IF
NA
R2
SIF
NB
1IF
NE
1IF
NG
IFN
GR
1IF
NG
R2
IFN
KIF
NW
1IG
HG
3IL
10
IL1
0R
AIL
10
RB
IL1
1IL
11
RA
IL1
2A
IL1
2B
IL1
2R
B1
IL1
2R
B2
IL1
3IL
13
RA
1IL
13
RA
2IL
15
IL1
5R
AIL
19
IL2
IL2
0IL
20
RA
IL2
1IL
21
RIL
22
IL2
2R
A1
MA
P_
Kin
ase
_S
ign
alin
g_
Pa
thw
ay
97
MA
P3
K7
SM
AP
4K
1M
AP
4K
3M
AP
K1
MA
PK
1)
MA
PK
10
MA
PK
11
MA
PK
12
MA
PK
13
MA
PK
14
MA
PK
3M
AP
K6
MA
PK
7M
AP
K8
MA
PK
8IP
2M
AP
K9
MA
PK
AP
K2M
AP
KA
PK
3MA
XM
EF
2C
MK
NK
1M
OS
MS
T1
MY
CN
FA
TC
4N
RA
SP
AK
1P
AK
3R
AC
1R
AC
2R
AF
1
Me
tab
olis
m_
of_
xe
no
bio
tics_
by_
cyto
ch
rom
e_
P4
50
_K
EG
G5
9K
Me
tal_
Tra
nsp
ort
_a
nd
_H
om
eo
sta
sis
94
SE
PN
1S
SE
PP
1S
EP
W1
SF
XN
2S
LC
11
A1
SL
C1
1A
2S
LC
30
A1
SL
C3
0A
3S
LC
30
A4
SL
C3
0A
5S
LC
30
A6
SL
C3
0A
8S
LC
31
A1
SL
C3
1A
2S
LC
39
A1
SL
C3
9A
2S
LC
39
A3
SL
C3
9A
4S
LC
39
A6
SL
C3
9A
7S
LC
40
A1
SO
D1
SO
D2
SP
S2
TF
TF
R2
TF
RC
UB
ET
HT
LR
4T
XN
RD
1T
XN
RD
2
Me
tallo
pro
tea
se
s3
4p
rese
nt_
stu
dy
Me
tasta
sis
_a
de
no
ca
rc_
dn
34
msig
db
Me
tasta
sis
_a
de
no
ca
rc_
up
14
msig
db
mT
OR
_sig
na
ling
_p
ath
wa
y_
KE
GG
49
K
Na
tura
l_kill
er_
ce
ll_m
ed
iate
d_
cyto
toxic
ity_
KE
GG
11
8N
CR
3K
NF
AT
5N
FA
TC
1N
FA
TC
2N
FA
TC
3N
FA
TC
4N
RA
SP
AK
1P
IK3
CA
PIK
3C
BP
IK3
CD
PIK
3C
GP
IK3
R1
PIK
3R
2P
IK3
R3
PIK
3R
5P
LC
G1
PL
CG
2P
PP
3C
AP
PP
3C
BP
PP
3C
CP
PP
3R
1P
RF
1P
RK
CA
PR
KC
B1
PR
KC
GP
TK
2B
PT
PN
11
PT
PN
6R
AC
1R
AC
2
Ne
uro
scie
nce
_Io
n_
Ch
an
ne
ls_
&_
Tra
nsp
ort
ers
10
4K
CN
N2
SK
CN
N3
KC
NN
4K
CN
Q1
KC
NQ
2K
CN
Q3
KC
NQ
4K
CN
S1
KC
NS
2K
CN
S3
LB
PP
LT
PS
CA
MP
2S
CN
1A
SC
N1
BS
CN
2A
2S
CN
2B
SC
N3
AS
CN
4A
SC
N5
AS
CN
7A
SC
N8
AS
CN
9A
SC
P2
SL
C1
5A
2S
LC
18
A1
SL
C1
8A
2S
LC
18
A3
SL
C1
A1
SL
C1
A2
SL
C1
A3
Ne
uro
tra
nsm
itte
r_R
ece
pto
rs_
an
d_
Re
gu
lato
rs1
07
GR
IN1
SG
RP
RH
CR
TR
2H
RH
3H
TR
1B
HT
R2
AH
TR
3A
HT
R3
BIC
A1
KC
NM
A1
KC
NM
B4
MA
OA
NM
BR
NM
UR
1N
MU
R2
NP
Y1
RN
PY
2R
PH
OX
2A
PP
YR
1P
RIM
A1
RA
B1
4R
AB
3A
RIM
S1
SL
C1
A3
SL
C5
A7
SL
C6
A1
SL
C6
A3
SL
C6
A4
SL
C6
A5
SL
C6
A8
SL
C6
A9
NF
kB
_S
ign
alin
g_
Pa
thw
ay
11
3M
AP
3K
7S
MA
P3
K7
IP1M
AP
3K
7IP
2MA
PK
14
MA
PK
3M
AP
K8
MY
D8
8N
AL
P1
2N
FK
B1
NF
KB
2N
FK
BIA
PL
K2
PP
M1
AP
PP
5C
RA
F1
RE
LR
EL
AR
EL
BR
FP
2R
HO
AR
HO
CR
IPK
1R
IPK
2S
LC
20
A1
ST
AT
1T
BK
1T
ICA
M2
TL
R1
TL
R1
0T
LR
2T
LR
3
Nitric_
Oxid
e1
73
GP
X5
SG
PX
6G
RIN
2D
GS
SH
BG
1H
LA
-DR
AH
MO
X1
HP
RT
1H
RM
T1
L1
HR
MT
1L
2H
SP
A4
HS
PC
AH
SP
CB
ICA
M1
IGF
BP
1IL
10
IL1
BIL
2IL
4IL
6IL
8IL
KIN
SJU
NJU
NB
KR
T1
LA
MC
1L
OC
49
38
69L
PO
MA
DC
AM
1M
BL
2
Nitro
ge
n_
me
tab
olis
m_
KE
GG
24
K
No
tch
_S
ign
alin
g_
Pa
thw
ay
13
0IL
2R
AS
IVL
JA
G1
JA
G2
KR
T1
KR
T1
0K
RT
14
KR
T5
LF
NG
LM
O2
LO
RL
RP
5M
AM
L1
MA
ML
2M
AM
L3
MA
P1
BM
AP
2K
7M
AP
KA
PK
3ME
CT
1M
FN
GM
GC
61
59
8M
MP
7M
YC
L1
NC
OR
2N
CS
TN
NE
UR
LN
FK
B1
NF
KB
2N
OT
CH
1N
OT
CH
2N
OT
CH
2N
L
Nu
cle
ar_
Re
ce
pto
rs_
an
d_
Co
reg
ula
tors
11
4N
R2
F6
SN
R3
C1
NR
3C
2N
R4
A1
NR
4A
2N
R4
A3
NR
5A
1N
R5
A2
NR
6A
1N
RIP
1P
CA
FP
GR
PG
RM
C2
PP
AR
AP
PA
RB
PP
PA
RD
PP
AR
GP
PA
RG
C1
APP
AR
GC
1BP
RIC
28
5P
SM
C3
PS
MC
5P
TG
ER
3R
AR
AR
AR
BR
AR
GR
BM
14
RB
PS
UH
RE
BB
PR
IPK
3R
NF
14
Oxid
ative
_p
ho
sp
ho
ryla
tio
n_
KE
GG
11
5N
DU
FA
10
KN
DU
FA
11
ND
UF
A1
2N
DU
FA
13
ND
UF
A2
ND
UF
A3
ND
UF
A4
ND
UF
A4
L2
ND
UF
A5
ND
UF
A6
ND
UF
A7
ND
UF
A8
ND
UF
A9
ND
UF
AB
1N
DU
FB
1N
DU
FB
10
ND
UF
B1
1N
DU
FB
2N
DU
FB
3N
DU
FB
4N
DU
FB
5N
DU
FB
6N
DU
FB
7N
DU
FB
8N
DU
FB
9N
DU
FC
1N
DU
FC
2N
DU
FS
1N
DU
FS
2N
DU
FS
3N
DU
FS
4
Oxid
ative
_S
tre
ss_
an
d_
An
tio
xid
an
t_D
efe
nse
84
PR
NP
SP
TG
S1
PT
GS
2P
XD
NP
XD
NL
RN
F7
SC
AR
A3
SE
LS
SE
PP
1S
FT
PD
SG
K2
SIR
T2
SO
D1
SO
D2
SO
D3
SR
XN
1S
TK
25
TP
OT
TN
TX
ND
C2
TX
NR
D1
TX
NR
D2
p5
3_
Sig
na
ling
_P
ath
wa
y1
13
MY
CS
MY
OD
1N
DR
G1
NF
1N
FK
B1
P5
3A
IP1
PC
AF
PC
BP
4P
HB
PL
AG
L1
PL
K1
PM
LP
MP
22
PP
M1
DP
PP
1R
13
BP
PP
1R
9B
PR
KC
AP
RK
CQ
PT
EN
PT
TG
1P
YC
AR
DR
AI
RB
1R
EL
AR
PR
MS
CG
B3
A1
SE
SN
1S
ES
N2
SE
SN
3S
FN
SH
C1
Pa
sse
rin
i_P
rolif
era
tio
n6
5IL
6m
sig
db
PP
M1
DF
LT
3
Ph
osp
ha
tase
s1
05
DU
PD
1p
rese
nt_
stu
dy
EP
M2
AR
NG
TT
ST
YX
SS
H1
SS
H2
SS
H3
PT
P4
A1
PT
P4
A2
PT
P4
A3
CD
C1
4A
CD
C1
4B
CD
KN
3P
TP
DC
1P
TE
NT
PT
E2
TP
TE
TN
S1
TE
NC
1M
TM
1M
TM
R1
MT
MR
2M
TM
R4
SB
F1
MT
MR
6M
TM
R8
MT
MR
9S
BF
2A
CP
1C
DC
25
AC
DC
25
B
PI3
K-A
KT
_S
ign
alin
g_
Pa
thw
ay
11
3M
AP
K8
SM
AP
K8
IP1
MK
NK
1M
LL
T7
MT
CP
1M
YD
88
NF
KB
1N
FK
BIA
PA
BP
C1
PA
K1
PD
GF
RA
PD
K1
PD
K2
PD
PK
1P
IK3
CA
PIK
3C
BP
IK3
CG
PIK
3R
1P
IK3
R2
PIK
3R
3P
R4
8P
RK
AR
1B
PR
KC
AP
RK
CB
1P
RK
CZ
PT
EN
PT
K2
PT
PN
11
RA
C1
RA
F1
RA
SA
1
PP
AR
_sig
na
ling
_p
ath
wa
y_
KE
GG
67
SL
C2
7A
5K
SL
C2
7A
6S
OR
BS
1U
BC
UC
P1
Pro
life
ratio
n_
Sig
na
ture
51
Wh
itfie
ld e
t a
l.
Pro
tea
so
me
_K
EG
G3
1K
Re
cu
rre
nce
_S
co
re1
6
Re
gu
latio
n_
of_
actin
_cyto
ske
leto
n_
KE
GG
20
1F
GF
21
KF
GF
22
FG
F2
3F
GF
3F
GF
4F
GF
5F
GF
6F
GF
7F
GF
8F
GF
9F
GF
R1
FG
FR
2F
GF
R3
FG
FR
4F
KS
G3
0F
N1
GIT
1G
NA
12
GN
A1
3G
NG
12
GR
LF
1G
SN
HR
AS
INS
IQG
AP
1IQ
GA
P2
IQG
AP
3IT
GA
10
ITG
A1
1IT
GA
2IT
GA
2B
Re
gu
latio
n_
of_
au
top
ha
gy_
KE
GG
28
K
Rib
ofla
vin
_m
eta
bo
lism
_K
EG
G1
6K
Rib
oso
me
_K
EG
G8
6R
PS
19
KR
PS
2R
PS
20
RP
S2
1R
PS
23
RP
S2
4R
PS
25
RP
S2
6R
PS
27
RP
S2
7A
RP
S2
7L
RP
S2
8R
PS
29
RP
S3
RP
S3
AR
PS
4X
RP
S4
Y1
RP
S5
RP
S6
RP
S7
RP
S8
RP
S9
RP
SA
UB
A5
2
Ro
tte
rda
m_
sig
na
ture
68
OR
12
D2
Ja
nse
n e
t a
l.R
PL
23
AP
7P
HF
11
///
RT
ME
M8
NE
FL
AC
AC
B
Sh
ep
ard
_ce
ll_p
rolif
era
tio
n2
32
PT
CH
msig
db
FS
CN
1E
NP
EP
RB
BP
7IR
F2
CD
K7
PR
KC
AS
TA
T6
AR
HG
EF
1B
UB
1B
EP
S8
MK
I67
KR
T1
6P
RK
CM
CD
C1
4A
BS
69
EG
FR
TF
DP
1L
RP
AP
1IG
FB
P4
CU
L5
TP
X2
FT
H1
IL1
AL
AT
S1
CD
K3
EP
HB
4C
SF
1C
SE
1L
KIF
2C
PR
L
Sh
ep
ard
_n
eg
_re
g_
of_
ce
ll_p
rolif
era
tio
n1
16
BC
L2
msig
db
CU
L1
UM
OD
IGF
BP
6M
DM
2V
HL
ML
LT
7B
AI1
SS
TR
1N
F1
CD
KN
2A
AIF
1R
AR
RE
S1
ITM
1F
AB
P3
NF
2C
DK
N2
BC
GR
RF
1P
OU
1F
1S
ST
R3
SS
TO
PR
M1
ND
NF
AB
P6
CU
L5
TN
FR
SF
8P
AW
RIL
1A
CU
L4
AC
UL
2T
OB
2
Sig
na
l_T
ran
sd
uctio
n_
in_
Ca
nce
r9
8p
21
Cip
1S
PE
CA
M1
PG
RP
IG3
PP
AR
GP
TC
HP
TC
H2
PT
GS
2S
LC
2A
1T
FT
FR
CT
ME
PA
IT
NF
TN
FA
IP3
TN
FR
SF
10
TN
FR
SF
6T
NF
SF
10
TP
53
TR
AF
1V
CA
M1
VE
GF
WIG
1W
ISP
1W
NT
1W
NT
2W
SB
1Z
NF
14
7A
2M
AB
CB
1A
DR
A1
BA
KT
1
Sig
na
l_T
ran
sd
uctio
n_
Pa
thw
ay_
Fin
de
r1
14
IRF
1S
JU
NJU
NB
KL
K2
KL
K3
LE
F1
LE
PL
TA
MD
M2
MM
P1
0M
MP
-7M
YC
NA
B2
NF
KB
1N
FK
BIA
NO
S2
AN
RIP
1O
DC
1P
EC
AM
1P
GR
PP
AR
GP
RK
CA
PR
KC
B1
PR
KC
EP
TC
HP
TC
H2
PT
GS
2R
BB
P8
RB
P1
RB
P2
SE
LE
Sp
hin
go
lipid
_m
eta
bo
lism
_K
EG
G3
7K
Str
ess_
&_
To
xic
ity_
Pa
thw
ay_
Fin
de
r9
6M
DM
2S
MIF
MT
2A
NF
KB
1N
FK
BIA
NO
S2
AP
CN
AP
OR
PR
DX
1P
RD
X2
PT
GS
1P
TG
S2
RA
D2
3A
RA
D5
0S
ER
PIN
E1
SO
D1
SO
D2
TN
FT
NF
RS
F1
AT
NF
SF
10
TN
FS
F6
TP
53
TR
AD
DU
GT
1A
10
UN
GX
RC
C1
XR
CC
2X
RC
C4
XR
CC
5C
AT
CC
L3
Str
ess_
Re
sp
on
se
_to
_C
ellu
lar_
Da
ma
ge
96
HS
F1
SH
SP
A1
2A
HS
PA
2H
SP
A4
HS
PA
5H
SP
A6
HS
PA
8H
SP
A9
BH
SP
B1
HS
PB
2H
SP
B3
HS
PC
AH
SP
CB
HS
PD
1H
SP
E1
HS
PH
1H
YO
U1
MA
OA
MA
OB
MG
ST
1N
AT
2N
NM
TN
UD
T1
PO
N3
PP
IDS
ER
PIN
H1
SO
D1
SO
D2
ST
13
TC
P1
TP
MT
T_
ce
ll_re
ce
pto
r_sig
na
ling
_p
ath
wa
y_
KE
GG
92
PA
K6
KP
AK
7P
DC
D1
PD
K1
PIK
3C
AP
IK3
CB
PIK
3C
DP
IK3
CG
PIK
3R
1P
IK3
R2
PIK
3R
3P
IK3
R5
PL
CG
1P
PP
3C
AP
PP
3C
BP
PP
3C
CP
PP
3R
1P
RK
CQ
PT
PN
6P
TP
RC
RA
SG
RP
1R
HO
AS
OS
1S
OS
2T
EC
TN
FV
AV
1V
AV
2V
AV
3Z
AP
70
T-c
ell_
an
d_
B-c
ell_
Activa
tio
n6
6IL
2R
AS
IL3
IL3
1R
AIL
4
TG
F-b
eta
_sig
na
ling
_p
ath
wa
y1
16
ID1
SID
2ID
3ID
4IF
NG
IGF
1IG
FB
P3
IL6
INH
BA
INH
BB
INH
BC
INH
BE
LE
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KE
GG
90
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To
xic
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&_
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g_
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73
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11
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2
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Tu
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59
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FR
SF
25
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FR
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NF
RS
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FS
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NF
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15
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Tu
mo
r_S
up
pre
sso
r2
6m
sig
db
Tyro
sin
e_
me
tab
olis
m_
KE
GG
55
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Un
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rhill
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era
tio
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GG
69
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17
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16
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Ca
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na
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wa
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KE
GG
17
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Re
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69
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CL
11
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13
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18
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KE
GG
65
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Da
ma
ge
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alin
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Pa
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53
TP
73
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82
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me
mb
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18
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PC
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61
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10
TS
PA
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13
TS
PA
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15
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17
TS
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31
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33
EC
M_
pro
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50
84
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11
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13
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15
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KL
K6
KL
K7
KL
K8
KL
K9
EC
M-r
ece
pto
r_in
tera
ctio
n_
KE
GG
85
K
EG
F_
PD
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ign
alin
g_
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96
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53
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12
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10
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FR
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10
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11
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Fo
ca
l_a
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n_
KE
GG
19
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LA
MA
4L
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LA
MB
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LA
MB
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13
18
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10
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Fo
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sis
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97
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Ge
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32
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51
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16
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Ge
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11
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Sig
na
ling
99
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na
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96
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Gro
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dg
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na
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55
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alin
g_
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thw
ay
48
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pa
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ay
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sig
db
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sig
db
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kin
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&_
Re
ce
pto
rs9
3S
Ino
sito
l_p
ho
sp
ha
te_
me
tab
olis
m_
KE
GG
51
K
Insu
lin_
Sig
na
ling
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ath
wa
y1
71
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CK
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CK
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KP
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PK
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PP
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D
Inte
rfe
ron
84
S
Inte
rfe
ron
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et
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37
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52
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16
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95
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39
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87
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17
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29
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97
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94
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49
K
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ce
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ity_
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11
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RA
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SH
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SH
C3
SH
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FR
SF
10
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FR
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10
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FR
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10
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FR
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10
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Ne
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ne
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Tra
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10
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25
A4
SL
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5A
5S
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29
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A1
SL
C2
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1S
LC
33
A1
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C3
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11
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C6
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2
Ne
uro
tra
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d_
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gu
lato
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07
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PA
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kB
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alin
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11
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TL
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RS
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10
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A
Nitric_
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GF
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LA
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Nitro
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n_
me
tab
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m_
KE
GG
24
K
No
tch
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ign
alin
g_
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13
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TC
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NO
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UP
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H
Nu
cle
ar_
Re
ce
pto
rs_
an
d_
Co
reg
ula
tors
11
4S
RO
RA
RO
RB
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RC
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RA
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RG
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3S
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RA
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TH
RA
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TH
RA
P4
TH
RA
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TH
RA
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RB
TIF
1T
RE
RF
1T
RIP
4V
DR
Oxid
ative
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sp
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tio
n_
KE
GG
11
5K
ND
UF
S5
ND
UF
S6
ND
UF
S7
ND
UF
S8
ND
UF
V1
ND
UF
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PP
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PP
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HC
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HD
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Oxid
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ss_
an
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tio
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84
S
p5
3_
Sig
na
ling
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ath
wa
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13
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MA
RC
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ST
AT
1T
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LT
NF
TN
FR
SF
10
TN
FS
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TP
53
TP
53
BP
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TR
AF
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sig
db
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tase
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pre
se
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10
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MR
11
MT
MR
12
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01
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5
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alin
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11
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PT
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SL
WN
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HZ
FY
VE
21
PP
AR
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na
ling
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ath
wa
y_
KE
GG
67
K
Pro
life
ratio
n_
Sig
na
ture
51
Wh
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t a
l.
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tea
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me
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cu
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6
Re
gu
latio
n_
of_
actin
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ske
leto
n_
KE
GG
20
1K
ITG
A3
ITG
A4
ITG
A5
ITG
A6
ITG
A7
ITG
A8
ITG
A9
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B2
ITG
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B7
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LIM
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CK
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SM
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SM
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GG
28
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m_
sig
na
ture
68
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nse
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t a
l.
Sh
ep
ard
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rolif
era
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n2
32
msig
db
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RP
INF
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PR
G4
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C2
L2
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NA
IL3
FE
ST
NF
RS
F9
AK
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NC
DK
4K
NS
L7
TH
PO
UN
Q4
29
CD
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3C
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1
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16
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RS
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ING
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ES
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TS
1C
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AN
CK
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F
Sig
na
l_T
ran
sd
uctio
n_
in_
Ca
nce
r9
8S
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XB
MP
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2H
SF
1IC
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1
Sig
na
l_T
ran
sd
uctio
n_
Pa
thw
ay_
Fin
de
r1
14
SS
EL
PL
GT
AN
KT
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7T
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TT
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CT
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PA
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10
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ess_
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xic
ity_
Pa
thw
ay_
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AJA
1
Str
ess_
Re
sp
on
se
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lar_
Da
ma
ge
96
ST
RA
1U
GT
1A
10
XD
H
T_
ce
ll_re
ce
pto
r_sig
na
ling
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ath
wa
y_
KE
GG
92
K
T-c
ell_
an
d_
B-c
ell_
Activa
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6S
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F-b
eta
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na
ling
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ath
wa
y1
16
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MA
D1
SM
AD
2S
MA
D3
SM
AD
5S
MA
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SM
AD
7S
MA
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SM
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F1
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UR
F2
SP
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FD
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FB
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GF
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FB
3T
GF
BR
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GF
BR
2T
HB
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TH
BS
2T
HB
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TH
BS
4T
NF
ZF
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E1
6Z
FY
VE
9
Th
1-T
h2
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36
2S
Tig
ht_
jun
ctio
n_
KE
GG
11
4K
PR
KC
EP
RK
CG
PR
KC
HP
RK
CI
PR
KC
QP
RK
CZ
PT
EN
RA
B1
3R
AB
3B
RH
OA
RR
AS
RR
AS
2S
PT
AN
1S
RC
SY
MP
KT
JA
P1
TJP
1T
JP
2V
AP
AY
ES
1Z
AK
TN
F_
L&
R2
8S
To
ll-lik
e_
rece
pto
r_sig
na
ling
_p
ath
wa
y_
KE
GG
90
K
To
xic
olo
gy_
&_
Dru
g_
Re
sis
tan
ce
73
S
TS
P1
_p
ath
wa
y7
S
Tu
mo
r_M
eta
sta
sis
59
S
Tu
mo
r_N
ecro
sis
_F
acto
r7
0S
Tu
mo
r_S
up
pre
sso
r2
6m
sig
db
Tyro
sin
e_
me
tab
olis
m_
KE
GG
55
K
Un
de
rhill
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rolif
era
tio
n1
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nd
erh
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t a
l.
VE
GF
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na
ling
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ath
wa
y_
KE
GG
69
K
vV
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en
e_
Sig
na
ture
61
va
n't
Ve
er
et
al.
Wn
t_S
ign
alin
g_
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thw
ay
17
5S
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AR
DP
PP
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AP
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2C
BP
PP
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1A
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PP
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2A
PP
P2
R2
BP
PP
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2C
PP
P3
CA
PP
P3
CB
PP
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CC
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P3
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LE
1P
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KL
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PR
KA
CA
PR
KA
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PR
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CG
PR
KC
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it.ed
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K=K
EGG
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Can
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2003
Feb;
3(2)
:185
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Potti
etal
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atM
ed.2
006
Nov
;12(
11):1
294-
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2002
Jun;
13(6
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Dec
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etal
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Apr
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Proc
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. 200
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200
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tig
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g_
an
d_
pre
se
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n_
KE
GG
73
K
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op
tosis
16
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RE
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RIP
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FT
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RS
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18
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FS
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53
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nce
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alin
g1
01
msig
db
Ca
lciu
m_
sig
na
ling
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ath
wa
y_
KE
GG
17
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LC
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PL
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PP
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CA
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PP
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PR
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PT
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45
HR
YR
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YR
2R
YR
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LC
25
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LC
25
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SL
C8
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Ce
ll_a
dh
esio
n_
mo
lecu
les_
(CA
Ms)_
KE
GG
12
5K
VC
AM
1
Ce
ll_C
ycle
89
S
Ce
ll_P
rolif
era
tio
n7
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nw
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et
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ula
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65
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Da
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10
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56
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82
S
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61
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24
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26
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28
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KE
GG
85
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alin
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96
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12
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19
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97
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95
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99
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51
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71
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14
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49
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KE
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11
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nce
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10
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d_
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S
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alin
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11
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73
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Nitro
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me
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GG
24
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13
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67
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GG
20
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14
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5
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GG
28
K
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vin
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me
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sig
na
ture
68
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ep
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60
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6
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16
msig
db
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na
l_T
ran
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uctio
n_
in_
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nce
r9
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na
l_T
ran
sd
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n_
Pa
thw
ay_
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de
r1
14
S
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hin
go
lipid
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lism
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&_
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xic
ity_
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thw
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de
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6S
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ess_
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sp
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lar_
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ma
ge
96
S
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ce
ll_re
ce
pto
r_sig
na
ling
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ath
wa
y_
KE
GG
92
K
T-c
ell_
an
d_
B-c
ell_
Activa
tio
n6
6S
TG
F-b
eta
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na
ling
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ath
wa
y1
16
S
Th
1-T
h2
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36
2S
Tig
ht_
jun
ctio
n_
KE
GG
11
4K
TN
F_
L&
R2
8S
To
ll-lik
e_
rece
pto
r_sig
na
ling
_p
ath
wa
y_
KE
GG
90
K
To
xic
olo
gy_
&_
Dru
g_
Re
sis
tan
ce
73
S
TS
P1
_p
ath
wa
y7
S
Tu
mo
r_M
eta
sta
sis
59
S
Tu
mo
r_N
ecro
sis
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acto
r7
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mo
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up
pre
sso
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6m
sig
db
Tyro
sin
e_
me
tab
olis
m_
KE
GG
55
K
Un
de
rhill
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rolif
era
tio
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ling
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ath
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GG
69
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vV
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na
ture
61
va
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er
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al.
Wn
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alin
g_
Pa
thw
ay
17
5S
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CK
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2S
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P1
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RP
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RP
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OX
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TT
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1T
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1Y
TC
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TC
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L1
TC
F7
L2
TL
E1
TL
E2
TL
E3
TL
E4
TP
53
VA
NG
L1
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NG
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1
NO
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tsan
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indi
cate
d(m
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ase
http
://w
ww
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ad.m
it.ed
u/gs
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jsp,
K=K
EGG
,S=w
ww
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rarr
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Rose
nwal
det
al.
Can
cerC
ell.
2003
Feb;
3(2)
:185
-97,
Potti
etal
.N
atM
ed.2
006
Nov
;12(
11):1
294-
300,
Whi
tfiel
det
al.
Mol
Bio
lC
ell.
2002
Jun;
13(6
):197
7-20
00,P
aik
etal
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Engl
JM
ed.2
004
Dec
30;3
51(2
7):2
817-
26,K
lijn
etal
.J
Clin
Onc
ol.2
006
Apr
10;2
4(11
):166
5-71
,Sh
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det
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Proc
N
atl A
cad
Sci U
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. 200
5 Se
p 13
;102
(37)
:131
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hill
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. 200
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t al.
Nat
ure.
200
2 Ja
n 31
;415
(687
1):5
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.
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pre
se
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n_
KE
GG
73
K
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op
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16
3S
TP
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TP
73
LT
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DD
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lciu
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17
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85
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96
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12
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19
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95
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96
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55
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48
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51
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71
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89
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17
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97
S
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tal_
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94
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se
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stu
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49
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11
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51
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of_
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n_
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GG
20
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sig
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68
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ran
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nce
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ran
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n_
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14
S
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ma
ge
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S
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ce
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ce
pto
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na
ling
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wa
y_
KE
GG
92
K
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d_
B-c
ell_
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tio
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6S
TG
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eta
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na
ling
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ath
wa
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16
S
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36
2S
Tig
ht_
jun
ctio
n_
KE
GG
11
4K
TN
F_
L&
R2
8S
To
ll-lik
e_
rece
pto
r_sig
na
ling
_p
ath
wa
y_
KE
GG
90
K
To
xic
olo
gy_
&_
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g_
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sis
tan
ce
73
S
TS
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ath
wa
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S
Tu
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sta
sis
59
S
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sig
db
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sin
e_
me
tab
olis
m_
KE
GG
55
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de
rhill
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rolif
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t a
l.
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GF
_sig
na
ling
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ath
wa
y_
KE
GG
69
K
vV
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e_
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na
ture
61
va
n't
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er
et
al.
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t_S
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alin
g_
Pa
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ay
17
5S
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0B
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16
WN
T2
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T2
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NT
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NO
TE:N
umbe
rofg
enes
pres
enti
nea
chge
nese
tsan
dso
urce
are
indi
cate
d(m
sigd
b=M
olec
ular
Sign
atur
esD
atab
ase
http
://w
ww
.bro
ad.m
it.ed
u/gs
ea/m
sigd
b/in
dex.
jsp,
K=K
EGG
,S=w
ww
.supe
rarr
ay.c
om,
Rose
nwal
det
al.
Can
cerC
ell.
2003
Feb;
3(2)
:185
-97,
Potti
etal
.N
atM
ed.2
006
Nov
;12(
11):1
294-
300,
Whi
tfiel
det
al.
Mol
Bio
lC
ell.
2002
Jun;
13(6
):197
7-20
00,P
aik
etal
.N
Engl
JM
ed.2
004
Dec
30;3
51(2
7):2
817-
26,K
lijn
etal
.J
Clin
Onc
ol.2
006
Apr
10;2
4(11
):166
5-71
,Sh
epar
det
al.
Proc
N
atl A
cad
Sci U
S A
. 200
5 Se
p 13
;102
(37)
:131
94-9
, U
nder
hill
et a
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lood
. 200
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ay 1
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1(10
):401
3-21
, van
't Ve
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t al.
Nat
ure.
200
2 Ja
n 31
;415
(687
1):5
30-6
.
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nce
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sis
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3S
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tig
en
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g_
an
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pre
se
nta
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n_
KE
GG
73
K
Ap
op
tosis
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3S
Bre
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nce
r_E
str
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en
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alin
g1
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msig
db
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lciu
m_
sig
na
ling
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ath
wa
y_
KE
GG
17
1K
Ce
ll_a
dh
esio
n_
mo
lecu
les_
(CA
Ms)_
KE
GG
12
5K
Ce
ll_C
ycle
89
S
Ce
ll_P
rolif
era
tio
n7
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ald
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al.
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em
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an
d_
Re
ce
pto
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S
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lore
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l_ca
nce
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EG
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mm
on
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kin
e1
08
S
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mp
lem
en
t_a
nd
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ag
ula
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n_
ca
sca
de
s_
KE
GG
65
K
DN
A_
Da
ma
ge
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ign
alin
g_
Pa
thw
ay
10
7S
EC
M_
extr
ace
llula
r1
56
S
EC
M_
inh
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rs&
oth
er_
en
zym
es
82
S
EC
M_
me
mb
ran
e_
ce
ll-ce
ll_a
dh
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n1
38
S
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me
mb
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ce
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n1
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PP
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SS
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TS
P5
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18
87
UN
Q9
39
1X
PN
PE
P2
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ece
pto
r_in
tera
ctio
n_
KE
GG
85
K
EG
F_
PD
GF
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ign
alin
g_
Pa
thw
ay
96
S
En
do
the
lial_
Ce
ll_B
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gy
12
1S
Fo
ca
l_a
dh
esio
n_
KE
GG
19
3K
VC
LV
EG
FV
EG
FB
VE
GF
CV
TN
VW
FZ
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Fo
late
_b
iosyn
the
sis
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EG
G3
7K
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Pro
tein
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up
led
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ece
pto
r9
6S
G_
Pro
tein
-Co
up
led
_R
ece
pto
r_II
97
S
Ga
p_
jun
ctio
n_
KE
GG
95
K
Ge
ne
s_
co
nstitu
tin
g_
the
_P
I3_
kin
ase
_p
red
icto
r1
32
Po
tti e
t a
l.
Ge
no
me
_S
tab
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ase
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://w
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jsp,
K=K
EGG
,S=w
ww
.supe
rarr
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Rose
nwal
det
al.
Can
cerC
ell.
2003
Feb;
3(2)
:185
-97,
Potti
etal
.N
atM
ed.2
006
Nov
;12(
11):1
294-
300,
Whi
tfiel
det
al.
Mol
Bio
lC
ell.
2002
Jun;
13(6
):197
7-20
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Engl
JM
ed.2
004
Dec
30;3
51(2
7):2
817-
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lijn
etal
.J
Clin
Onc
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006
Apr
10;2
4(11
):166
5-71
,Sh
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det
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Proc
N
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S A
. 200
5 Se
p 13
;102
(37)
:131
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hill
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Nat
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200
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28
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90
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73
S
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m_
KE
GG
55
K
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1
Supplemental Table 2a. Pearson correlation analysis of each MMP and COX-2 with OPN expression profiles.
In the table are reported number of genes present in each geneset extracted from the datasets and source (K=KEGG, S=www.superarray.com, Rosenwald et al.
Cancer Cell. 2003 Feb;3(2):185-97, Potti et al. Nat Med. 2006 Nov;12(11):1294-300, Whitfield et al. Mol Biol Cell. 2002 Jun;13(6):1977-2000, Paik et al. N
Engl J Med. 2004 Dec 30;351(27):2817-26, Klijn et al. J Clin Oncol. 2006 Apr 10;24(11):1665-71, Shepard et al. Proc Natl Acad Sci U S A. 2005 Sep
13;102(37):13194-9, Underhill et al. Blood. 2003 May 15;101(10):4013-21, van't Veer et al. Nature. 2002 Jan 31;415(6871):530-6. Normalized Enrichment
Score (NES), Nominal P Value (NOM), False Discovery Rate (FDR). Statistical threshold: enrichment with either both normalized p value < 0.01 and FDR
<0.25 or at least one of the two parameters below the selected value.
Supplemental Table 3b. List of gene sets significantly enriched (shaded areas) in association to MMP-9 in at least one gene
expression dataset generated by oligo nucleotide microarray platform.
GENESETS POSITIVELY ENRICHED WITH MMP9 IN DATASET:
In the table are reported number of genes present in each geneset extracted from the datasets and source (K=KEGG, S=www.superarray.com, Rosenwald et al.
Cancer Cell. 2003 Feb;3(2):185-97, Potti et al. Nat Med. 2006 Nov;12(11):1294-300, Whitfield et al. Mol Biol Cell. 2002 Jun;13(6):1977-2000, Paik et al. N
Engl J Med. 2004 Dec 30;351(27):2817-26, Klijn et al. J Clin Oncol. 2006 Apr 10;24(11):1665-71, Shepard et al. Proc Natl Acad Sci U S A. 2005 Sep
13;102(37):13194-9, Underhill et al. Blood. 2003 May 15;101(10):4013-21, van't Veer et al. Nature. 2002 Jan 31;415(6871):530-6. Normalized Enrichment
Score (NES), Nominal P Value (NOM), False Discovery Rate (FDR). Statistical threshold: enrichment with either both normalized p value < 0.01 and FDR
<0.25 or at least one of the two parameters below the selected value.
Supplemental Table 4a. List of genes from the CELL_PROLIFERATION gene sets and their association with
