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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
pp
lem
en
tary
Ta
ble
1.
Lis
t o
f g
en
e s
ets
an
d g
en
es f
or
GS
EA
.
GE
NE
SE
TS
N
. G
en
es
So
urc
eG
en
e S
ym
pb
ol
Ad
he
ren
s_
jun
ctio
n_
_K
EG
G7
5K
AC
P1
AC
TB
AC
TC
1A
CT
G1
AC
TN
1A
CT
N2
AC
TN
3A
CT
N4
AC
VR
1B
AC
VR
1C
BA
IAP
2C
DC
42
CD
H1
CR
EB
BP
CS
NK
2A
1C
SN
K2
A2
CS
NK
2B
CT
NN
A1
CT
NN
A2
CT
NN
A3
CT
NN
B1
CT
NN
D1
EG
FR
EP
30
0E
RB
B2
FA
RP
2F
ER
FG
FR
1F
KS
G3
0F
YN
IGF
1R
An
dro
ge
n_
Sig
na
ling
_a
nd
_P
rosta
te_
Ca
nce
r9
6S
AC
PP
AD
H1
BA
DM
AK
R1
B1
AL
DH
1A
1A
NK
HA
PO
EA
RS
DR
1A
S3
C7
CD
C3
7C
DH
1C
DS
1C
HD
4C
LU
CS
NK
2B
CS
TB
CY
P2
C1
8D
BI
DH
CR
24
DK
FZ
P4
34
EIF
4E
BP
1F
AT
FB
XL
11
FG
F8
FK
BP
5F
KB
P8
FO
LH
1F
OX
J1
GA
GE
B1
GA
GE
C1
An
gio
ge
ne
sis
11
3S
AK
T1
AN
GP
T1
AN
GP
T2
AN
GP
TL
3A
NG
PT
L4
AN
PE
PB
AI1
CC
L1
1C
CL
2C
DH
5C
OL
18
A1
CO
L4
A3
CS
F3
CX
CL
1C
XC
L1
0C
XC
L1
1C
XC
L2
CX
CL
3C
XC
L5
CX
CL
6C
XC
L9
EC
GF
1E
DG
1E
FN
A1
EF
NA
2E
FN
A3
EF
NA
5E
FN
B2
EG
FE
NG
EP
AS
1
An
tig
en
_p
roce
ssin
g_
an
d_
pre
se
nta
tio
n_
KE
GG
73
KB
2M
CA
LR
CA
NX
CD
4C
D7
4C
D8
AC
D8
BC
IIT
AC
RE
B1
CT
SB
CT
SL
CT
SS
HL
A-A
HL
A-B
HL
A-C
HL
A-D
MB
HL
A-D
OA
HL
A-D
OB
HL
A-D
PA
1H
LA
-DP
B1
HL
A-D
QA
1H
LA
-DQ
A2
HL
A-D
QB
1H
LA
-DQ
B2
HL
A-D
RA
HL
A-D
RB
1H
LA
-DR
B4
HL
A-E
HL
A-F
HL
A-G
HS
P9
0A
A1
Ap
op
tosis
16
3S
AB
L1
AK
T1
AK
T2
AK
T3
AP
AF
1A
TM
BA
DB
AG
1B
AG
3B
AG
4B
AK
1B
AX
BC
L1
0B
CL
2B
CL
2A
1B
CL
2L
1B
CL
2L
10
BC
L2
L1
1B
CL
2L
12
BC
L2
L1
3B
CL
2L
2B
CL
AF
1B
FA
RB
IDB
IKB
IRC
1B
IRC
2B
IRC
3B
IRC
4B
IRC
5B
IRC
6
Bre
ast_
Ca
nce
r_E
str
og
en
_S
ign
alin
g1
01
msig
db
SP
RR
1B
PA
PP
AN
ME
1A
TF
2F
3C
TS
DC
LD
N7
TO
P2
AC
TN
NB
1M
AP
2K
7M
T3
ITG
A6
TF
F3
PT
GS
2F
HL
5M
LP
PL
AU
IL6
RC
CN
E1
TP
53
ID2
CC
NE
2IG
FB
P2
GA
TA
3R
AC
2C
D4
4G
SN
ITG
B4
ER
BB
2C
CN
A1
CC
ND
1
Ca
lciu
m_
sig
na
ling
_p
ath
wa
y_
KE
GG
17
1K
AD
CY
1A
DC
Y2
AD
CY
3A
DC
Y4
AD
CY
7A
DC
Y8
AD
CY
9A
DO
RA
2A
AD
OR
A2
BA
DR
A1
AA
DR
A1
BA
DR
A1
DA
DR
B1
AD
RB
2A
DR
B3
AG
TR
1A
TP
2A
1A
TP
2A
2A
TP
2A
3A
TP
2B
1A
TP
2B
2A
TP
2B
3A
TP
2B
4A
VP
R1
AA
VP
R1
BB
DK
RB
2B
ST
1C
AC
NA
1A
CA
CN
A1
BC
AC
NA
1C
CA
CN
A1
D
Ce
ll_a
dh
esio
n_
mo
lecu
les_
(CA
Ms)_
KE
GG
12
5K
AL
CA
MC
D2
CD
22
CD
22
6C
D2
74
CD
27
6C
D2
8C
D3
4C
D4
CD
40
CD
40
LG
CD
58
CD
6C
D8
0C
D8
6C
D8
AC
D8
BC
D9
9C
DH
1C
DH
15
CD
H2
CD
H3
CD
H4
CD
H5
CL
DN
1C
LD
N1
0C
LD
N1
1C
LD
N1
4C
LD
N1
5C
LD
N1
6C
LD
N1
7
Ce
ll_C
ycle
89
SC
KS
1B
SF
NY
WH
AQ
GS
K3
BY
WH
AZ
MK
I67
PT
TG
1R
BX
1R
BB
P8
CK
S2
CC
ND
2G
AD
D4
5A
CH
EK
1C
DC
20
BU
B3
CC
NA
2C
CN
B1
CD
KN
2A
RA
D1
7P
LK
1R
PA
3M
CM
4C
DK
7M
NA
T1
SU
MO
1H
DA
C2
CH
EK
2E
P3
00
MC
M3
CC
NB
2B
UB
1B
Ce
ll_P
rolif
era
tio
n7
2R
ose
nw
ald
et
al.
TG
FA
TA
CS
TD
2T
NF
SF
9K
RT
16
ME
TG
PC
4E
GF
RE
PH
B4
IL1
BM
YC
IL2
RG
PT
HL
HIL
1A
FZ
D3
EM
P2
IL6
RS
FN
ISG
20
PD
GF
AZ
FP
36
L2
EH
FT
NF
RS
F9
MIA
AR
HG
EF
1G
AB
1N
R6
A1
TA
L1
PIM
2M
T3
ND
PN
UD
C
Ch
em
okin
e_
Lig
an
d_
Re
ce
pto
r1
69
S C
CL
15
CC
L3
L1
C
CL
3L
3
CC
R2
CC
R3
CC
R5
CC
R8
CX
CR
2L
OC
72
88
3L
OC
73
04
2B
DN
FC
20
orf
17
5C
5C
CB
P2
CC
L1
CC
L1
C
CL
11
CC
L1
1
CC
L1
2
CC
L1
3C
CL
13
C
CL
14
C
CL
15
CC
L1
5
CC
L1
6C
CL
16
C
CL
17
CC
L1
7
CC
L1
8C
CL
18
C
CL
19
Co
lore
cta
l_ca
nce
r_K
EG
G7
8K
AC
VR
1B
AC
VR
1C
AK
T1
AK
T2
AK
T3
AP
CA
PC
2A
PP
LA
XIN
1A
XIN
2B
AD
BA
XB
CL
2B
IRC
5C
AS
P3
CA
SP
9C
CN
D1
CT
NN
B1
CY
CS
DC
CD
VL
1D
VL
2D
VL
3E
GF
RF
OS
FZ
D1
FZ
D1
0F
ZD
2F
ZD
3F
ZD
4F
ZD
5
Co
mm
on
_C
yto
kin
e1
08
SA
TP
6A
P1
BM
P1
0B
MP
15
BM
P2
BM
P3
BM
P4
BM
P5
BM
P6
BM
P7
BM
P8
BC
SF
1C
SF
2C
SF
3C
YF
IP2
FA
M3
BF
AM
3C
FA
SL
GF
GF
10
FL
T3
LG
GD
F1
0G
DF
11
GD
F1
5G
DF
2G
DF
3G
DF
5G
DF
8G
DF
9IF
NA
13
IFN
A1
4IF
NA
2IF
NA
4
Co
mp
lem
en
t_a
nd
_co
ag
ula
tio
n_
ca
sca
de
s_
KE
GG
65
KA
2M
BD
KR
B2
C1
QA
C1
QB
C1
QC
C1
RC
1S
C2
C3
C3
AR
1C
4B
PA
C4
BP
BC
5C
5A
R1
C6
C7
C8
AC
8B
C8
GC
D4
6C
D5
5C
D5
9C
FB
CF
DC
FH
CF
IC
PB
2C
R1
CR
2F
10
F1
1
DN
A_
Da
ma
ge
_S
ign
alin
g_
Pa
thw
ay
10
7S
AN
KR
D1
7A
TM
AT
RX
BR
CA
1B
TG
2C
CN
HC
DK
7C
HE
K2
CIB
1C
IDE
AC
IDE
BC
KN
1C
RY
1C
RY
2D
DB
1D
DB
2D
DIT
3D
MC
1E
RC
C1
ER
CC
2E
RC
C3
ER
CC
4E
RC
C5
EX
O1
FA
NC
GF
EN
1G
22
P1
GA
DD
45
AG
AD
D4
5G
GM
LG
TF
2H
1
EC
M_
extr
ace
llula
r1
56
SA
DIP
OQ
AG
C1
AM
EL
XA
ME
LY
BC
AN
BG
NC
LU
CO
L1
0A
1C
OL
11
A1
CO
L1
1A
2C
OL
12
A1
CO
L1
3A
1C
OL
14
A1
CO
L1
5A
1C
OL
16
A1
CO
L1
7A
1C
OL
18
A1
CO
L1
9A
1C
OL
1A
1C
OL
1A
2C
OL
20
A1
CO
L2
1A
1C
OL
22
A1
CO
L2
3A
1C
OL
24
A1
CO
L2
5A
1C
OL
27
A1
CO
L2
A1
CO
L3
A1
CO
L4
A1
CO
L4
A2
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
-TC
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
AM
6
EC
M_
me
mb
ran
e_
ce
ll-m
atr
ix_
ad
he
sio
n1
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
ITF
G2
ITF
G3
ITG
A1
0IT
GA
11
ITG
A2
ITG
A2
BIT
GA
3IT
GA
4IT
GA
5IT
GA
6IT
GA
7IT
GA
8IT
GA
9IT
GA
DIT
GA
EIT
GA
L
EC
M_
pro
tea
se
s2
04
SA
CE
AC
E2
AD
AM
1A
DA
M1
0A
DA
M1
1A
DA
M1
2A
DA
M1
5A
DA
M1
7A
DA
M1
8A
DA
M1
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
CO
L1
1A
2C
OL
1A
1C
OL
1A
2C
OL
2A
1C
OL
3A
1C
OL
4A
1C
OL
4A
2C
OL
4A
4C
OL
4A
6C
OL
5A
1C
OL
5A
2C
OL
5A
3C
OL
6A
1C
OL
6A
2C
OL
6A
3D
AG
1F
N1
FN
DC
1F
ND
C3
AF
ND
C4
FN
DC
5G
P1
BA
GP
5G
P6
GP
9
EG
F_
PD
GF
_S
ign
alin
g_
Pa
thw
ay
96
SA
CT
R2
AC
TR
3A
KT
1A
KT
2A
KT
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
CR
EB
1C
SN
K2
A1
CS
NK
2B
DU
SP
1D
US
P6
EG
FE
GF
RE
GR
1E
IF4
EE
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
H5
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
AD
BC
AR
1B
CL
2B
IRC
2B
IRC
3B
IRC
4B
RA
FC
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
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18
FP
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DT
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Pro
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DO
RA
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A3
AG
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G_
Pro
tein
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up
led
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pto
r_II
97
SA
DR
A1
AA
DR
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BA
DR
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AA
DR
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BA
DR
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B2
AD
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BL
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CC
R1
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R2
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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
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3C
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CR
6C
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LT
R1
DR
D1
Ga
p_
jun
ctio
n_
KE
GG
95
KA
DC
Y1
AD
CY
2A
DC
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AD
CY
4A
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AD
CY
6A
DC
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8A
DC
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AD
RB
1C
DC
2C
SN
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1A
1L
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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
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NA
SG
RB
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RM
1
Ge
ne
s_
co
nstitu
tin
g_
the
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kin
ase
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r1
32
Po
tti e
t a
l.A
KR
7A
3A
NK
RD
32
AT
AD
2B
AR
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rf1
17
C1
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C2
1o
rf4
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50
CA
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8A
P2
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NE
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CD
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CD
C7
CD
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FE
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FIG
NL
1
Ge
no
me
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ility
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11
3S
AN
KR
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PE
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AT
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CD
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EX
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J1
08
58
G2
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3
G-P
rote
in_
Co
up
led
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ece
pto
rs_
Sig
na
ling
99
SA
DR
B2
AG
TR
1A
GT
R2
AN
GP
TL
4A
RR
B1
AR
RB
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CL
2B
CL
2L
1C
AL
CR
CA
SR
CC
ND
1C
CN
E1
CC
NE
2C
DK
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BC
FL
AR
CM
KL
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CO
L1
A1
CS
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CT
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CY
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RD
1D
RD
2D
RD
5D
US
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4E
DG
1E
DG
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DG
3E
DG
4E
DG
5E
DG
7E
GR
1
G-P
rote
ins_
&_
Sig
na
ling
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ole
cu
les
96
SA
DC
Y1
AD
CY
3A
DC
Y4
AD
CY
5A
DC
Y6
AD
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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
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r8
4S
AM
HA
RT
S-1
BD
NF
BM
P1
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P1
0B
MP
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5B
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MP
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CS
F3
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PG
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K1
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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
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na
ling
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ath
wa
y_
KE
GG
55
KB
MP
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MP
4B
MP
5B
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7B
MP
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BT
RC
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XW
11
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23
Hyp
oxia
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ign
alin
g_
Pa
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ay
48
SA
DD
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DM
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AC
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BB
PC
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BC
TG
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DC
TN
2D
NA
JB
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EE
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pa
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ay
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sig
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12
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12
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SO
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30
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TK
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IF
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BP
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a
Infla
mm
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ry_
Cyto
kin
es_
&_
Re
ce
pto
rs9
3S
AB
CF
1B
CL
6B
LR
1C
3C
4A
C5
CC
L1
CC
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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
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CL
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CL
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CR
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CR
3C
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CR
5
Ino
sito
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ha
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me
tab
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KE
GG
51
KC
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rf9
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K4
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IMP
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IMP
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INP
P1
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Insu
lin_
Sig
na
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wa
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71
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CA
AC
AC
BA
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EB
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AK
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AK
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AN
GA
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CL
2L
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CC
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CE
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BC
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1
Inte
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ron
84
SA
DA
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FR
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LF
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AC
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CL
10
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NA
1IF
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14
IFN
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4IF
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5IF
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6
Inte
rfe
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Re
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se
96
SA
DA
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RL
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29
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85
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22
80
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19
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Inte
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Re
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rs7
1S
IL1
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11
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AIL
12
AF
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IL1
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10
RA
IL1
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2R
B1
IL1
2R
B2
IL1
3IL
13
RA
1IL
13
RA
2IL
14
IL1
5IL
15
RA
IL1
6IL
17
IL1
7B
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7C
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7F
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18
BP
IL1
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18
RA
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19
IL1
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Inva
siv
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ess_
Ge
ne
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ign
atu
re1
89
Liu
et
al.
CL
TC
LD
HA
DN
AJB
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1C
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PS
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1C
OP
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PL
P2
RA
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PS
MA
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H3
BG
RL
EM
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NR
PN
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TC
10
OR
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LT
FD
PF
2JT
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MG
PG
NP
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LF
10
NS
FM
AP
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4S
TK
39
RN
F8
HS
2S
T1
CN
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4S
TC
2S
TA
MS
RP
54
JA
K_
ST
AT
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ign
alin
g_
Pa
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ay
17
9S
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MA
KT
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2A
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PS
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CB
LC
BL
BC
BL
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CD
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CS
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RC
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2C
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1
MA
P_
Kin
ase
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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
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CO
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A1
CR
EB
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RE
BB
PD
LK
1D
US
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EG
FR
Me
tab
olis
m_
of_
xe
no
bio
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by_
cyto
ch
rom
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P4
50
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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
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AL
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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
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CY
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DH
DH
EP
HX
1G
ST
A1
Me
tal_
Tra
nsp
ort
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nd
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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
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RN
AS
E1
MA
OB
AC
AD
SB
PL
P1
CH
RN
A5
NR
4A
1N
CA
PH
ZN
F1
48
P2
RX
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PP
5E
PT
NN
R2
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JM
JD
1C
FX
NP
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6A
PR
KG
2R
AB
30
Me
tasta
sis
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de
no
ca
rc_
up
14
msig
db
PR
MT
1C
OL
1A
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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
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na
ling
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ath
wa
y_
KE
GG
49
KA
KT
1A
KT
2A
KT
3B
RA
FC
AB
39
DD
IT4
EIF
4B
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4E
EIF
4E
2E
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P1
FIG
FF
RA
P1
GB
LH
IF1
AIG
F1
INS
KIA
A1
30
3L
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AP
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MA
PK
3P
DP
K1
PG
FP
IK3
CA
PIK
3C
BP
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CD
PIK
3C
GP
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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
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BH
CS
TH
LA
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LA
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LA
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LA
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LA
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RA
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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
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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
CY
P7
A1
CY
P7
B1
DD
B1
DD
IT3
DN
AJB
4E
2F
1E
GR
1E
PH
X2
ER
CC
1E
RC
C3
ER
CC
4E
RC
C5
Str
ess_
Re
sp
on
se
_to
_C
ellu
lar_
Da
ma
ge
96
SA
CA
DS
BB
AG
1C
AL
RC
AN
XC
AT
CC
T2
CC
T3
CC
T4
CC
T5
CC
T7
CC
T8
CE
S1
CL
UC
RY
AA
CR
YA
BC
YP
11
A1
CY
P1
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11
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NA
JA
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JA
2
T_
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wa
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KE
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92
KA
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10
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11
CB
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BL
BC
BL
CC
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47
CD
28
CD
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CD
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CD
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GC
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42
CD
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28
CD
33
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12
TG
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16
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10
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36
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15
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69
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80
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86
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46
39
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Tig
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11
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42
CD
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CG
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10
CL
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11
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14
CL
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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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10
TN
FS
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18
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To
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90
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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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36
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59
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61
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;12(
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16
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21
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51
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10
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23
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RP
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Ch
em
okin
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Lig
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Re
ce
pto
r1
69
SC
CL
19
C
CL
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CL
2
CC
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20
C
CL
21
CC
L2
1
CC
L2
2C
CL
22
C
CL
23
CC
L2
3
CC
L2
4C
CL
24
C
CL
25
CC
L2
5
CC
L2
6C
CL
26
C
CL
27
CC
L2
7
CC
L2
8C
CL
3C
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3
CC
L4
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4L
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5C
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5
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7C
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7
CC
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Co
lore
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GR
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RA
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EF
1M
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10
MA
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MS
H2
MS
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MS
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MY
CP
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FR
AP
DG
FR
BP
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BP
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5
Co
mm
on
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kin
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08
SIF
NA
5IF
NA
8IF
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1IF
NG
IFN
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NW
1IL
10
IL1
1IL
12
AIL
12
BIL
13
IL1
4IL
15
IL1
6IL
17
IL1
7B
IL1
7C
IL1
7E
IL1
7F
IL1
8IL
19
IL1
AIL
1B
IL1
F1
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1F
5IL
1F
6IL
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7IL
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8IL
1F
9IL
2IL
20
Co
mp
lem
en
t_a
nd
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ula
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n_
ca
sca
de
s_
KE
GG
65
KF
12
F1
3A
1F
13
BF
2F
2R
F3
F5
F7
F8
F9
FG
AF
GB
FG
GK
LK
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KN
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PL
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PL
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PR
OC
PR
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1S
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PIN
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SE
RP
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5S
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PIN
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RP
IND
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PIN
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SE
RP
INF
2S
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PIN
G1
DN
A_
Da
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alin
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Pa
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ay
10
7S
GT
F2
H2
GT
F2
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GT
SE
1H
US
1IG
HM
BP
2IH
PK
3IN
PP
L1
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LIG
1L
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LIG
4M
AP
2K
6M
AP
K1
2M
BD
4M
LH
1M
LH
3M
NA
T1
MP
GM
RE
11
AM
SH
2M
SH
3M
SH
4M
SH
5M
SH
6M
UT
YH
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BP
2N
BS
1N
TH
L1
NU
DT
1O
GG
1P
CB
P4
EC
M_
extr
ace
llula
r1
56
SC
OL
4A
3C
OL
4A
3B
PC
OL
4A
4C
OL
4A
5C
OL
4A
6C
OL
5A
1C
OL
5A
2C
OL
5A
3C
OL
6A
1C
OL
6A
2C
OL
6A
3C
OL
7A
1C
OL
8A
1C
OL
8A
2C
OL
9A
1C
OL
9A
2C
OL
9A
3C
OL
QC
OM
PC
SP
G2
CS
PG
3C
SP
G4
CS
PG
4L
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G4
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PC
SP
G4
LY
PC
SP
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CS
PG
6C
TH
RC
1D
AG
1D
CN
DS
PG
3
EC
M_
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rs&
oth
er_
en
zym
es
82
SM
GE
A5
SE
RB
P1
SE
RP
INA
1S
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PIN
A1
0SE
RP
INA
12S
ER
PIN
A2
SE
RP
INA
3S
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PIN
A4
SE
RP
INA
5S
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PIN
A6
SE
RP
INA
7S
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PIN
A9
SE
RP
INB
1S
ER
PIN
B1
0SE
RP
INB
1S
ER
PIN
B1
2SE
RP
INB
13S
ER
PIN
B2
SE
RP
INB
3S
ER
PIN
B4
SE
RP
INB
5S
ER
PIN
B6
SE
RP
INB
7S
ER
PIN
B8
SE
RP
INB
9S
ER
PIN
C1
SE
RP
IND
1S
ER
PIN
E1
SE
RP
INE
2S
ER
PIN
F1
SE
RP
INF
2
EC
M_
me
mb
ran
e_
ce
ll-ce
ll_a
dh
esio
n1
38
SC
EA
CA
M7
CE
AC
AM
8C
EE
CA
M1
CE
LS
R1
CE
LS
R2
CE
LS
R3
CH
L1
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CA
MD
SC
AM
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FL
J2
55
30
ICA
M1
ICA
M2
ICA
M3
ICA
M4
ICA
M5
L1
CA
ML
OC
40
26
65L
OC
64
39
98M
AD
CA
M1
MC
AM
MU
CD
HL
NC
AM
1N
CA
M2
NR
CA
MO
PC
ML
PC
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CD
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H1
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PC
DH
12
PC
DH
15
PC
DH
17
EC
M_
me
mb
ran
e_
ce
ll-m
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ad
he
sio
n1
61
SIT
GA
MIT
GA
VIT
GA
XIT
GB
1IT
GB
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B1
BP
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GB
1B
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ITG
B2
ITG
B3
ITG
B3
BP
ITG
B4
ITG
B4
BP
ITG
B5
ITG
B6
ITG
B7
ITG
B8
ITG
BL
1L
MA
N1
LM
AR
CO
NE
TO
1N
ET
O2
NR
P1
NR
P2
NR
XN
1N
RX
N2
NR
XN
3P
GL
YR
P1
PG
LY
RP
2P
GL
YR
P3
PG
LY
RP
4P
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EC
M_
pro
tea
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s2
04
SA
DA
MD
EC
AD
AM
TS
1A
DA
MT
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0A
DA
MT
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1A
DA
MT
S1
2A
DA
MT
S1
3A
DA
MT
S1
4A
DA
MT
S1
5A
DA
MT
S1
6A
DA
MT
S1
7A
DA
MT
S1
8A
DA
MT
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9A
DA
MT
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AD
AM
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20A
DA
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1A
DA
MT
S3
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AM
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4A
DA
MT
S5
AD
AM
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6A
DA
MT
S7
AD
AM
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8A
DA
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S9
AD
AM
TS
L1A
DA
MT
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2A
DA
MT
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3A
DA
MT
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4A
DA
MT
SL
5C
OR
INC
PA
3C
PD
CP
E
EC
M-r
ece
pto
r_in
tera
ctio
n_
KE
GG
85
KH
MM
RH
SP
G2
IBS
PIT
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
LA
MA
1L
AM
A2
LA
MA
3L
AM
A4
LA
MA
5L
AM
B1
LA
MB
2L
AM
B3
LA
MB
4
EG
F_
PD
GF
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alin
g_
Pa
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ay
96
SG
AB
1G
RB
2G
SK
3A
GS
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BH
RA
SH
SP
A5
HS
PC
AH
SP
CB
ICA
M1
IGF
BP
1IK
BK
BIL
2IN
PP
5D
JA
K1
JU
NK
RA
S2
LT
AM
AP
2K
1M
AP
2K
4M
AP
2K
7M
AP
3K
1M
AP
3K
2M
AP
3K
3M
AP
3K
8M
AP
K1
MA
PK
10
MA
PK
3M
AP
K8
MA
PK
9M
KN
K1
MK
NK
2
En
do
the
lial_
Ce
ll_B
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gy
12
1S
CH
GA
CO
L1
8A
1C
PB
2C
RA
DD
CR
PC
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2C
SF
3C
X3
CL
1E
CG
F1
ED
G3
ED
N1
ED
N2
ED
N3
ED
NR
AE
DN
RB
EN
PE
PF
3F
GF
1F
GF
2F
LT
1F
LT
3F
LT
4F
N1
ICA
M1
ICA
M2
ICA
M3
ICE
BE
RG
IFN
B1
IL1
1IL
14
IL1
5
Fo
ca
l_a
dh
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n_
KE
GG
19
3K
CO
L2
A1
CO
L3
A1
CO
L4
A1
CO
L4
A2
CO
L4
A4
CO
L4
A6
CO
L5
A1
CO
L5
A2
CO
L5
A3
CO
L6
A1
CO
L6
A2
CO
L6
A3
CO
MP
CR
KC
RK
LC
TN
NB
1D
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CK
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GF
EG
FR
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BB
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FIG
FF
KS
G3
0F
LN
AF
LN
BF
LN
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LT
1F
N1
FY
N
Fo
late
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the
sis
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G3
7K
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TX
SM
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2S
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A5
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Pro
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up
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pto
r9
6S
ED
NR
AE
DN
RB
F2
RF
2R
L1
F2
RL
2F
2R
L3
FP
R1
FP
RL
1G
2A
GC
GR
GH
SR
GIP
RG
LP
2R
GP
R2
3G
PR
68
GR
B2
GR
M1
GR
M2
GR
M3
GR
M4
GR
M5
GR
M6
GR
M7
GR
M8
HR
H1
HR
H2
HR
H3
LH
CG
RL
TB
4R
LT
B4
R2
MC
1R
G_
Pro
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up
led
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ece
pto
r_II
97
SD
RD
2D
RD
3D
RD
5D
RIP
78
EB
FG
AB
RR
2G
PR
14
5G
PR
31
GP
R4
4G
PR
74
GP
RK
2L
GP
RK
5G
PR
K6
HM
74
HT
R1
AH
TR
1B
HT
R1
DH
TR
1E
HT
R1
FH
TR
2A
HT
R2
BH
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2C
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R3
AH
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4H
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5A
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IL8
RA
IL8
RB
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Ga
p_
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n_
KE
GG
95
KG
RM
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1A
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HT
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SM
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2K
2M
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2M
AP
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MA
PK
3M
AP
K7
NP
R1
NP
R2
NR
AS
PD
GF
BP
DG
FC
PD
GF
DP
DG
FR
A
Ge
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s_
co
nstitu
tin
g_
the
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r1
32
Po
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t a
l.F
LJ1
07
19
FL
J1
10
78
FL
J1
29
73
FL
J1
39
12
FL
J2
02
57
FL
J2
05
16
FL
J3
40
77
GA
DD
45
BG
AL
GA
S2
L1
GE
MIN
4G
MN
NG
PR
27
H2
AF
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SP
A1
AH
SP
A1
BID
1IE
R2
IL1
7D
IL1
7R
BIT
PK
CJP
H1
JU
NJU
NB
KC
TD
12
KIA
A0
15
3K
IAA
01
86
KIA
A0
40
6K
IAA
13
93
LE
F1
LM
NB
1
Ge
no
me
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tab
ility
_D
NA
_R
ep
air
11
3S
GT
F2
H4
KU
B3
LIG
1L
IG3
LIG
4M
BD
4M
GM
TM
LH
1M
LH
3M
MS
19
LM
NA
T1
MP
GM
RE
11
AM
SH
2M
SH
3M
SH
4M
SH
5M
SH
6M
UT
YH
N4
BP
2N
BS
1N
EIL
1N
EIL
2N
TH
L1
OG
G1
PA
RP
1P
AR
P3
PIN
X1
PM
S1
PM
S2
PM
S2
L1
G-P
rote
in_
Co
up
led
_R
ece
pto
rs_
Sig
na
ling
99
SE
LK
1E
LK
4F
3F
GF
2F
LJ1
02
10
FO
SG
NA
QG
NA
SG
NR
H1
GR
M2
GR
M4
GR
M7
GR
M8
HM
74
HS
D3
B1
HS
PA
4H
SP
CA
ICA
M1
IL1
BIL
1R
1IL
1R
2IL
2IL
4IL
6IL
8JU
NJU
NB
LH
BL
HC
GR
LO
C1
16
07
1MA
X
G-P
rote
ins_
&_
Sig
na
ling
_M
ole
cu
les
96
SG
NB
5G
NG
10
GN
G1
1G
NG
12
GN
G2
GN
G3
GN
G4
GN
G7
GN
GT
1G
NG
T2
GR
B2
HR
AS
JU
NK
RA
S2
MA
P2
K1
MA
P2
K2
MA
P2
K4
MA
P2
K5
MA
P3
K5
MA
PK
1M
AP
K3
MA
PK
7M
AP
K8
ME
F2
AN
FK
B1
NF
KB
IAN
RA
SP
DE
1A
PD
E1
BP
DE
4B
PD
PK
1
Gro
wth
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r8
4S
FG
F5
FG
F6
FG
F7
FG
F9
FIG
FG
DF
10
GD
F1
1G
DF
8G
DN
FG
PI
HB
EG
FIG
F1
IGF
2IL
10
IL1
1IL
12
BIL
18
IL1
AIL
1B
IL2
IL3
IL4
INH
AIN
HB
AIN
HB
BJA
G1
JA
G2
LE
FT
Y1
LE
FT
Y2
LIF
LT
BP
4
He
dg
eh
og
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na
ling
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ath
wa
y_
KE
GG
55
KS
HH
SM
OS
TK
36
SU
FU
WN
T1
WN
T1
0A
WN
T1
0B
WN
T1
1W
NT
16
WN
T2
WN
T2
BW
NT
3W
NT
3A
WN
T4
WN
T5
AW
NT
5B
WN
T6
WN
T7
AW
NT
7B
WN
T8
AW
NT
8B
WN
T9
AW
NT
9B
ZIC
2
Hyp
oxia
_S
ign
alin
g_
Pa
thw
ay
48
SE
GF
RE
GL
N2
EN
O1
EP
30
0E
PA
S1
EP
OF
NB
P3
FO
SG
AP
43
GN
A1
1G
PI
GP
X1
GS
TO
1H
BB
HIF
1A
HIF
1A
NH
IF3
A
IL1
8_
pa
thw
ay
6m
sig
db
IL3
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wa
y1
5m
sig
db
IL6
PA
TH
WA
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3m
sig
db
IL7
PA
TH
WA
Y1
8m
sig
db
Infla
mm
ato
ry_
Cyto
kin
es_
&_
Re
ce
pto
rs9
3S
CC
R6
CC
R7
CC
R8
CC
R9
CE
BP
BC
RP
CX
3C
L1
CX
3C
R1
CX
CL
1C
XC
L1
0C
XC
L1
1C
XC
L1
2C
XC
L1
3C
XC
L1
4C
XC
L2
CX
CL
3C
XC
L5
CX
CL
6C
XC
L9
CX
CR
4E
DG
3IC
EB
ER
GIF
NA
2IF
NG
IL1
0IL
10
RA
IL1
0R
BIL
11
IL1
1R
AIL
12
AIL
12
B
Ino
sito
l_p
ho
sp
ha
te_
me
tab
olis
m_
KE
GG
51
KP
IP5
K1
CP
IP5
K2
AP
IP5
K2
BP
IP5
K2
CP
IP5
K3
PL
CB
1P
LC
B2
PL
CB
3P
LC
B4
PL
CD
1P
LC
D3
PL
CD
4P
LC
E1
PL
CG
1P
LC
G2
PL
CZ
1P
TE
NS
KIP
SY
NJ1
SY
NJ2
Insu
lin_
Sig
na
ling
_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
LO
C6
53
87
9GO
LP
H2
SU
PT
16
HR
FX
DC
2Z
CC
HC
8U
CK
L1
AT
AD
2M
LF
1IP
C1
orf
66
CL
N8
PO
LQ
NC
AP
G2
KIA
A0
74
8G
AB
RQ
GF
OD
2B
CL
2L
14
Sh
ep
ard
_ce
ll_p
rolif
era
tio
n2
32
msig
db
CY
R6
1T
XN
OS
MR
MS
4A
1E
MP
3C
HR
M5
US
P8
INS
L4
IL2
RG
TC
F1
9IL
9R
PD
CD
1L
G1S
KB
1B
TG
1K
HD
RB
S1
RP
P1
4B
ST
2B
UB
1U
HR
F1
RP
S2
7S
IPA
1T
GF
AE
LN
TR
IPE
MP
1S
PO
CK
TG
FB
2C
KS
2M
ET
EL
F5
PY
Y
Sh
ep
ard
_n
eg
_re
g_
of_
ce
ll_p
rolif
era
tio
n1
16
msig
db
AD
RA
1A
BT
G1
CD
KN
1B
IL8
CD
KN
1C
AP
EG
1C
DK
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
3S
ST
R2
ET
S1
MX
I1Z
RA
NB
1
Sig
na
l_T
ran
sd
uctio
n_
in_
Ca
nce
r9
8S
FO
SF
OS
L1
FO
XA
2G
AD
D4
5A
HH
IPH
IF1
AH
K1
HM
OX
1H
SP
A4
HS
PA
5H
SP
B1
HS
PB
2H
SP
CA
ID2
IGF
BP
3IL
2IL
4IL
4R
IRF
1JU
NK
LK
2K
LK
3L
TA
MC
L1
MD
M2
MM
P1
0M
MP
7M
YC
NF
KB
1N
FK
BIA
NO
S2
A
Sig
na
l_T
ran
sd
uctio
n_
Pa
thw
ay_
Fin
de
r1
14
SC
XC
L1
2C
XC
L9
CY
P1
9A
1E
GF
RE
GR
1E
N1
FA
SN
FL
J1
25
41
FN
1F
OS
FO
XA
2G
AD
D4
5A
GR
EB
1G
YS
1H
HIP
HK
2H
OX
A1
HO
XB
1H
SF
1H
SP
B1
HS
PC
AIC
AM
1IG
FB
P3
IGF
BP
4IK
BK
BIL
1A
IL2
IL2
RA
IL4
IL4
RIL
8
Sp
hin
go
lipid
_m
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
F1
5G
PX
1G
SR
GS
TM
3H
MO
X1
HM
OX
2H
SF
1H
SP
A1
AH
SP
A1
LH
SP
A2
HS
PA
4H
SP
A5
HS
PA
6H
SP
A8
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
_C
ellu
lar_
Da
ma
ge
96
SD
NA
JA
3D
NA
JA
4D
NA
JB
1D
NA
JB
11
DN
AJB
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
X2
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
_p
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
_p
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
-Th
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
N9
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
_p
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
1H
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
3P
RM
T1
PR
MT
2P
RM
T3
PR
MT
5P
RM
T6
PR
MT
7P
RM
T8
SH
3G
LB
1T
AT
TH
TP
OT
YR
TY
RP
1
Un
de
rhill
_p
rolif
era
tio
n1
9n
de
rhill
et
al.
VE
GF
_sig
na
ling
_p
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
AL
M2
-AK
APE
CI
PIT
RM
1P
QL
C2
PR
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
en
es
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urc
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e S
ym
pb
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Ad
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ren
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ctio
n_
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FB
R1
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FB
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1V
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WA
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AS
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WA
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2W
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F3
WA
SL
YE
S1
An
dro
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n_
Sig
na
ling
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nd
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rosta
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Ca
nce
r9
6P
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PA
P2
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PA
P2
BP
SC
AP
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NR
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P1
AR
NF
14
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HB
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SR
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SR
EB
F2
ST
EA
PT
GF
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TG
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TM
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20
orf
1
An
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ne
sis
11
3L
EP
SM
DK
MM
P1
9M
MP
2M
MP
9N
OT
CH
4N
PP
BN
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
_p
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
-DR
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
LIT
GA
MIT
GA
VIT
GB
1IT
GB
2IT
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M2
JA
M3
L1
CA
MM
AD
CA
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MA
GM
PZ
MP
ZL
1
Ce
ll_C
ycle
89
CD
C7
SS
KP
1A
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M6
CD
K5
RA
P1B
CL
2C
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34
CD
K6
GT
SE
1C
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RO
RC
2L
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5C
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AP
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1
Ce
ll_P
rolif
era
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n7
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se
nw
ald
et
al.
BU
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UB
3P
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6M
NA
T1
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CP
1K
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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
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KL
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F2
CK
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3C
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F4
CK
LF
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CK
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7C
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Co
lore
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l_ca
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r_K
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RA
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RA
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RA
LG
DS
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AD
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MA
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SO
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SO
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F7
TG
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GF
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TG
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3T
GF
BR
1T
GF
BR
2T
P5
3
Co
mm
on
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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
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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
FT
Y2
LT
BP
1M
AP
K1
MA
PK
3M
YC
NO
DA
LN
OG
PIT
X2
PP
P2
CA
PP
P2
CB
RB
L1
RB
L2
RB
X1
RH
OA
RO
CK
1R
OC
K2
RP
S6
KB
1R
PS
6K
B2
SK
P1
A
Th
1-T
h2
-Th
36
2S
Tig
ht_
jun
ctio
n_
KE
GG
11
4L
OC
15
00
84
KM
AG
I1M
AG
I2M
AG
I3M
LL
T4
MP
DZ
MP
P5
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90
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11
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59
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FR
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25
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FS
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15
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Tu
mo
r_S
up
pre
sso
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sig
db
Tyro
sin
e_
me
tab
olis
m_
KE
GG
55
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Un
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GG
69
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17
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;12(
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17
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65
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17
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33
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84
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15
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ece
pto
r_in
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n_
KE
GG
85
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F_
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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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10
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11
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19
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13
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Fo
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97
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51
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48
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me
tab
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51
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Insu
lin_
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na
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71
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84
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52
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16
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17
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10
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13
95
15
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OB
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NX
6N
UC
KS
1X
PR
1G
TF
3C
3D
NM
T3
AZ
DH
HC
2C
1O
RF
16
3N
UD
T5
MG
C4
39
9S
ER
TA
D1
AN
KR
D1
3C
C7
OR
F3
6R
AB
23
LM
BR
1K
IAA
12
87
JA
K_
ST
AT
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ign
alin
g_
Pa
thw
ay
17
9S
IL2
2R
A2
IL2
3A
IL2
3R
IL2
4IL
26
IL2
8A
IL2
8B
IL2
8R
AIL
29
IL2
RA
IL2
RB
IL2
RG
IL3
IL3
1R
AIL
3R
AIL
4IL
4R
IL5
IL5
RA
IL6
IL6
RIL
6S
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7IL
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IL9
IL9
RIN
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INS
RIR
F1
ISG
F3
GJA
K1
MA
P_
Kin
ase
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ign
alin
g_
Pa
thw
ay
97
SR
B1
RP
S6
KA
5S
FN
TP
53
Me
tab
olis
m_
of_
xe
no
bio
tics_
by_
cyto
ch
rom
e_
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50
_K
EG
G5
9K
Me
tal_
Tra
nsp
ort
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nd
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om
eo
sta
sis
94
SV
EG
F
Me
tallo
pro
tea
se
s3
4p
rese
nt_
stu
dy
Me
tasta
sis
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de
no
ca
rc_
dn
34
msig
db
Me
tasta
sis
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de
no
ca
rc_
up
14
msig
db
mT
OR
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na
ling
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ath
wa
y_
KE
GG
49
K
Na
tura
l_kill
er_
ce
ll_m
ed
iate
d_
cyto
toxic
ity_
KE
GG
11
8K
RA
C3
RA
F1
SH
2D
1B
SH
3B
P2
SH
C1
SH
C2
SH
C3
SH
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SO
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SO
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SY
KT
NF
TN
FR
SF
10
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FR
SF
10
TN
FR
SF
10
TN
FR
SF
10
TN
FS
F1
0T
YR
OB
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LB
P1
UL
BP
2U
LB
P3
VA
V1
VA
V2
VA
V3
ZA
P7
0
Ne
uro
scie
nce
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n_
Ch
an
ne
ls_
&_
Tra
nsp
ort
ers
10
4S
SL
C2
5A
3S
LC
25
A4
SL
C2
5A
5S
LC
29
A1
SL
C2
A1
SL
C2
A1
1S
LC
33
A1
SL
C3
5B
1S
LC
6A
11
SL
C6
A1
2S
LC
6A
2
Ne
uro
tra
nsm
itte
r_R
ece
pto
rs_
an
d_
Re
gu
lato
rs1
07
SS
NA
P2
5S
NA
PA
PS
NP
HS
OR
CS
1S
OR
CS
2S
ST
R1
SS
TR
2S
ST
R3
SS
TR
4S
YN
1S
YN
2S
YN
3S
YT
1T
AC
R1
NF
kB
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ign
alin
g_
Pa
thw
ay
11
3S
TL
R4
TL
R6
TL
R7
TL
R8
TL
R9
TN
FT
NF
AIP
3T
NF
RS
F1
0T
NF
RS
F1
0T
NF
RS
F1
AT
NF
RS
F5
TN
FR
SF
7T
NF
SF
10
TN
FS
F1
4T
NF
SF
6T
RA
DD
TR
AF
5T
RA
F6
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IFV
AP
A
Nitric_
Oxid
e1
73
SM
MP
1M
MP
2M
MP
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MP
9M
PO
MR
P1
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TM
SR
AM
T1
GM
T3
MT
L5
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BM
YC
NC
AM
1N
CF
1N
CF
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FK
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NM
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NO
S1
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AN
OS
3N
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1O
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FA
PD
GF
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LA
2G
2D
PL
AT
PN
KP
Nitro
ge
n_
me
tab
olis
m_
KE
GG
24
K
No
tch
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ign
alin
g_
Pa
thw
ay
13
0S
NO
TC
H3
NO
TC
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PC
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PS
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EN
PT
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PT
CR
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BP
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BP
SU
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NG
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1S
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HS
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MO
SN
W1
SP
EN
ST
AT
6S
UF
US
UP
T6
H
Nu
cle
ar_
Re
ce
pto
rs_
an
d_
Co
reg
ula
tors
11
4S
RO
RA
RO
RB
RO
RC
RX
RA
RX
RB
RX
RG
SIX
3S
KII
PS
RC
AP
TG
FB
1I1
TH
RA
TH
RA
P1
TH
RA
P3
TH
RA
P4
TH
RA
P5
TH
RA
P6
TH
RB
TIF
1T
RE
RF
1T
RIP
4V
DR
Oxid
ative
_p
ho
sp
ho
ryla
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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ND
UF
V3
PP
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PP
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HA
SD
HB
SD
HC
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HD
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QC
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CR
Q
Oxid
ative
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ss_
an
d_
An
tio
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an
t_D
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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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CA
ST
AT
1T
AD
A3
LT
NF
TN
FR
SF
10
TN
FS
F6
TP
53
TP
53
BP
2T
P7
3T
P7
3L
TR
AF
2T
RA
F4
TR
AF
5T
SC
1T
SC
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Pa
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rolif
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sig
db
Ph
osp
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tase
s1
05
pre
se
nt_
stu
dy
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MR
10
MT
MR
11
MT
MR
12
KIA
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01
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MR
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5
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alin
g_
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11
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FT
CL
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PT
LR
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LIP
TS
C1
TS
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WA
SL
WN
T1
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HA
HZ
FY
VE
21
PP
AR
_sig
na
ling
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ath
wa
y_
KE
GG
67
K
Pro
life
ratio
n_
Sig
na
ture
51
Wh
itfie
ld e
t a
l.
Pro
tea
so
me
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EG
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cu
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nce
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co
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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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AE
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ITG
AM
ITG
AV
ITG
AX
ITG
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ITG
B2
ITG
B3
ITG
B4
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B5
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B6
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B7
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B8
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LIM
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MA
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CK
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SM
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SM
SN
Re
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latio
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of_
au
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KE
GG
28
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Rib
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vin
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lism
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Rib
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na
ture
68
Ja
nse
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l.
Sh
ep
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rolif
era
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n2
32
msig
db
SE
RP
INF
1P
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K1
PR
G4
CD
C2
L2
PC
NA
IL3
FE
ST
NF
RS
F9
AK
R1
C3
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NC
DK
4K
NS
L7
TH
PO
UN
Q4
29
CD
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1
Sh
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16
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7T
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RS
F9
ING
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ES
N1
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1C
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AN
CK
2P
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F
Sig
na
l_T
ran
sd
uctio
n_
in_
Ca
nce
r9
8S
BA
XB
MP
2C
DK
2H
SF
1IC
AM
1
Sig
na
l_T
ran
sd
uctio
n_
Pa
thw
ay_
Fin
de
r1
14
SS
EL
PL
GT
AN
KT
CF
7T
ER
TT
FR
CT
ME
PA
1T
NF
TN
FR
SF
10
TN
FR
SF
6T
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SF
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GF
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hin
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lipid
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lism
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Str
ess_
&_
To
xic
ity_
Pa
thw
ay_
Fin
de
r9
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NC
CD
KN
1A
DN
AJA
1
Str
ess_
Re
sp
on
se
_to
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ellu
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
tio
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6S
TG
F-b
eta
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na
ling
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ath
wa
y1
16
SS
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
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SP
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FB
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GF
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TG
FB
3T
GF
BR
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GF
BR
2T
HB
S1
TH
BS
2T
HB
S3
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
9U
nd
erh
ill e
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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2C
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PP
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1A
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PP
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2A
PP
P2
R2
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PP
2R
2C
PP
P3
CA
PP
P3
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PP
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CC
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P3
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LE
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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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Feb;
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:185
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;12(
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2002
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tig
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g_
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d_
pre
se
nta
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n_
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GG
73
K
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op
tosis
16
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RE
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RIP
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RS
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18
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FS
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TP
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53
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nce
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alin
g1
01
msig
db
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lciu
m_
sig
na
ling
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ath
wa
y_
KE
GG
17
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LC
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PP
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45
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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
al.
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Re
ce
pto
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GP
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09
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16
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88
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ula
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65
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ge
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10
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56
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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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51
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na
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71
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17
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14
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49
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d_
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KE
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11
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nce
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ers
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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n_
me
tab
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m_
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GG
24
K
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13
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11
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67
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Sig
na
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51
Wh
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GG
20
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14
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5
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latio
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of_
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top
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KE
GG
28
K
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vin
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sig
na
ture
68
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l.
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ep
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32
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g_
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ce
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16
msig
db
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na
l_T
ran
sd
uctio
n_
in_
Ca
nce
r9
8S
Sig
na
l_T
ran
sd
uctio
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
on
se
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lar_
Da
ma
ge
96
S
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
tio
n6
6S
TG
F-b
eta
_sig
na
ling
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ath
wa
y1
16
S
Th
1-T
h2
-Th
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
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
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t a
l.
VE
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na
ling
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ath
wa
y_
KE
GG
69
K
vV
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0g
en
e_
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na
ture
61
va
n't
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er
et
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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HF
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SIA
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LC
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D2
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AD
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OX
17
TT
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1X
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L1
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1T
BL
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
VA
NG
L2
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1
NO
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pres
enti
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chge
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tsan
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indi
cate
d(m
sigd
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Sign
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http
://w
ww
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ad.m
it.ed
u/gs
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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
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
epar
det
al.
Proc
N
atl A
cad
Sci U
S A
. 200
5 Se
p 13
;102
(37)
:131
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hill
et a
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. 200
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Nat
ure.
200
2 Ja
n 31
;415
(687
1):5
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.
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r9
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sis
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3S
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tig
en
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ssin
g_
an
d_
pre
se
nta
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n_
KE
GG
73
K
Ap
op
tosis
16
3S
TP
73
TP
73
LT
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DD
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AF
1T
RA
F2
TR
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3T
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F4
TR
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5
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nce
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en
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ign
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
SL
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SL
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A3
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ym
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lT
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C2
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Ce
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n_
mo
lecu
les_
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KE
GG
12
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Ce
ll_C
ycle
89
S
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ll_P
rolif
era
tio
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ose
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ald
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al.
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okin
e_
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an
d_
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ce
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r1
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SS
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2T
CP
10
TL
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TL
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FT
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94
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20
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92
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36
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KE
GG
11
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R2
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ll-lik
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rece
pto
r_sig
na
ling
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wa
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KE
GG
90
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xic
olo
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g_
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sis
tan
ce
73
S
TS
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59
S
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sin
e_
me
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KE
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de
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na
ling
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KE
GG
69
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vV
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na
ture
61
va
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et
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alin
g_
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17
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16
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T2
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NO
TE:N
umbe
rofg
enes
pres
enti
nea
chge
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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
3 M
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
.
Pa
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an
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KE
GG
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K
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nce
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str
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g1
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lciu
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sig
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ling
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wa
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17
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mo
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KE
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12
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ll_C
ycle
89
S
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en
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ula
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n_
ca
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de
s_
KE
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65
K
DN
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Da
ma
ge
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ign
alin
g_
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thw
ay
10
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M_
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56
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S
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me
mb
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18
87
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39
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n_
KE
GG
85
K
EG
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GF
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ign
alin
g_
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thw
ay
96
S
En
do
the
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gy
12
1S
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ca
l_a
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KE
GG
19
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sis
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up
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ece
pto
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G_
Pro
tein
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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
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kin
ase
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red
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r1
32
Po
tti e
t a
l.
Ge
no
me
_S
tab
ility
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NA
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ep
air
11
3S
G-P
rote
in_
Co
up
led
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ece
pto
rs_
Sig
na
ling
99
S
G-P
rote
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&_
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na
ling
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les
96
S
Gro
wth
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acto
r8
4S
He
dg
eh
og
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na
ling
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ath
wa
y_
KE
GG
55
K
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oxia
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ign
alin
g_
Pa
thw
ay
48
S
IL1
8_
pa
thw
ay
6m
sig
db
IL3
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ath
wa
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sp
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ma
ge
96
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ce
ll_re
ce
pto
r_sig
na
ling
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ath
wa
y_
KE
GG
92
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ath
wa
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16
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urce
are
indi
cate
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sigd
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ular
Sign
atur
esD
atab
ase
http
://w
ww
.bro
ad.m
it.ed
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sigd
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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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200
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28
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ath
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ath
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GG
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g_
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sis
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73
S
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S
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59
S
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55
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GG
69
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ture
61
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Wn
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enes
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tsan
dso
urce
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indi
cate
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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
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Supplemental Table 2a. Pearson correlation analysis of each MMP and COX-2 with OPN expression profiles.
r P r P r P r P r P r P r P
4312 MMP1 0.01 0.983 0.04 0.818 0.05 0.815 0.43 0.070 0.13 0.235 -0.23 0.101
4313 MMP2 -0.15 0.264 -0.38 0.036 0.01 0.966 -0.42 0.067 0.13 0.231 -0.15 0.282
4314 MMP3 0.06 0.714 -0.31 0.271 -0.33 0.072 0.15 0.537 -0.17 0.479 0.02 0.875 -0.20 0.095
4316 MMP7 0.14 0.255 0.19 0.514 0.35 0.054 0.15 0.531 -0.20 0.410 0.34 0.001 0.27 0.052
4317 MMP8 -0.13 0.500 -0.08 0.730 0.05 0.854 -0.01 0.901 -0.25 0.069
4318 MMP9 0.37 0.015 0.50 0.037 0.18 0.337 0.15 0.508 0.76 0.000 0.32 0.002 0.47 0.000
4319 MMP10 -0.32 0.374 0.21 0.277 0.36 0.116 0.23 0.368 0.36 0.001 -0.34 0.012
4320 MMP11 0.12 0.483 0.27 0.142 0.45 0.046 0.33 0.164 0.35 0.001 -0.46 0.001
4321 MMP12 -0.11 0.660 0.13 0.658 -0.14 0.460 0.46 0.052 0.77 0.000 0.26 0.010 -0.47 0.001
4322 MMP13 0.06 0.649 0.03 0.874 0.24 0.310 0.33 0.167 0.01 0.913 -0.19 0.158
4323 MMP14 -0.27 0.031 -0.29 0.120 0.30 0.187 0.33 0.163 0.19 0.070 -0.13 0.385
4324 MMP15 0.05 0.725 0.18 0.342 0.22 0.351 -0.06 0.811 0.28 0.009 -0.36 0.008
4325 MMP16 -0.02 0.857 0.34 0.067 0.40 0.081 -0.54 0.014 0.14 0.178 -0.39 0.006
4326 MMP17 0.14 0.342 -0.07 0.726 0.03 0.912 0.12 0.626 -0.08 0.474
4327 MMP19 -0.18 0.153 -0.34 0.064 0.23 0.328 -0.61 0.006 0.01 0.907
9313 MMP20 -0.25 0.376 -0.09 0.649 0.00 0.990 0.31 0.192 0.05 0.661 -0.15 0.306
8510 MMP23B -0.17 0.369 -0.24 0.306 0.11 0.651 -0.02 0.828 -0.03 0.827
10893 MMP24 0.01 0.964 -0.18 0.544 -0.32 0.083 -0.27 0.247 -0.50 0.028 0.19 0.081
64386 MMP25 -0.44 0.114 0.19 0.305 0.23 0.333 -0.02 0.952
56547 MMP26 -0.33 0.390 0.10 0.614 0.07 0.780 -0.03 0.905
64066 MMP27 -0.02 0.878 -0.02 0.915 0.56 0.011 0.25 0.329
79148 MMP28 0.15 0.442 -0.23 0.331 -0.45 0.055
5743 COX-2 -0.31 0.053 -0.14 0.443 0.21 0.275 -0.10 0.709 -0.13 0.606 0.26 0.024 -0.09 0.194
V VI VIII II III IV
Dataset*
ID GeneSymbol
Shaded areas indicate statistically significant correlations by Pearson analysis. * For identification of datasets, see Table 1.
2
Supplemental Table 2b. Pearson correlation analysis of each randomly picked gene with OPN expression profiles.
r P r P r P r P r P r P r P
321 APBA2 -0.07 0.664 0.15 0.447 0.10 0.123 -0.07 0.789 0.70 0.001 0.13 0.097 0.01 0.937
377 ARF3 0.17 0.327 0.12 0.518 -0.73 0.000 -0.12 0.675 0.17 0.472 0.31 0.005 -0.07 0.212
8703 B4GALT3 0.30 0.065 -0.22 0.247 -0.70 0.000 -0.34 0.148 0.03 0.908 0.26 0.035 -0.24 0.084
657 BMPR1A -0.24 0.151 -0.33 0.074 -0.61 0.000 0.32 0.119 -0.50 0.030 0.18 0.116 0.49 0.000
928 CD9 0.08 0.647 0.07 0.717 -0.54 0.003 0.08 0.704 -0.73 0.000 0.15 0.118 0.23 0.094
1105 CHD1 -0.06 0.739 0.61 0.001 -0.64 0.000 0.14 0.552 -0.08 0.745 -0.22 0.029 0.09 0.544
1649 DDIT3 0.02 0.921 0.20 0.305 -0.25 0.091 -0.09 0.706 0.37 0.111 0.12 0.152 0.31 0.026
1798 DPAGT1 0.03 0.848 0.19 0.316 -0.74 0.000 -0.14 0.582 -0.57 0.011 0.04 0.728 0.14 0.337
2125 EVPL 0.15 0.370 -0.18 0.362 0.58 0.001 -0.04 0.858 -0.48 0.039 -0.18 0.057 -0.10 0.476
3553 IL1B 0.32 0.329 0.32 0.108 -0.08 0.719 0.18 0.423 -0.16 0.520 0.05 0.475 0.20 0.159
9858 KIAA0649 -0.25 0.129 0.17 0.388 -0.35 0.059 -0.13 0.570 0.60 0.005 0.10 0.348 -0.19 0.182
4085 MAD2L1 -0.18 0.260 0.11 0.567 -0.43 0.016 -0.13 0.506 0.74 0.001 -0.08 0.377 0.22 0.108
23118 MAP3K7IP2 0.03 0.842 0.04 0.821 -0.20 0.300 0.08 0.760 -0.42 0.068 0.01 0.933 0.18 0.184
4361 MRE11A -0.17 0.303 -0.15 0.414 -0.47 0.008 0.19 0.419 0.52 0.025 -0.15 0.127 0.30 0.029
4818 NKG7 0.72 0.020 0.85 0.000 0.23 0.069 -0.36 0.024 -0.28 0.164 -0.40 0.094 -0.29 0.000
55746 NUP133 -0.09 0.577 -0.25 0.198 -0.72 0.000 0.04 0.848 0.06 0.795 -0.27 0.007 0.25 0.049
8473 OGT -0.02 0.928 0.21 0.277 -0.68 0.000 0.05 0.786 0.09 0.707 0.04 0.624 0.11 0.433
26986 PABPC1 0.03 0.859 -0.56 0.001 0.18 0.107 -0.17 0.314 -0.01 0.970 0.44 0.053 0.45 0.000
5581 PRKCE -0.50 0.133 -0.12 0.515 -0.07 0.696 -0.09 0.755 0.06 0.817 -0.22 0.007 0.08 0.569
22929 SEPHS1 0.02 0.885 0.19 0.300 -0.08 0.692 -0.17 0.379 0.49 0.032 0.04 0.672 0.40 0.003
10915 TCERG1 0.28 0.087 0.01 0.947 0.00 0.991 -0.02 0.905 0.69 0.001 -0.01 0.934 0.04 0.848
7381 UQCRB -0.31 0.054 0.25 0.179 -0.06 0.768 0.34 0.142 0.27 0.264 -0.24 0.011 0.35 0.010
7405 UVRAG -0.31 0.053 -0.14 0.443 0.21 0.275 -0.10 0.709 -0.13 0.606 0.26 0.024 -0.09 0.194
Dataset*
VIIIII IV V VIID GeneSymbol
I II
Shaded areas indicate statistically significant correlations by Pearson analysis. * For identification of datasets, see Table 1.
Supplemental Table 3a. List of gene sets significantly enriched (shaded areas) in association to OPN in at least one gene expression
dataset generated by oligo nucleotide microarray platform.
GENESETS POSITIVELY ENRICHED WITH OPN IN DATASET:
NOM FDR NOM FDR NOM FDR NOM FDR NOM FDR
p-val q-val p-val q-val p-val q-val p-val q-val p-val q-val
ANGIOGENESIS 109 S 0.81 0.7138 0.8930 1.56 0.0228 1.0000 1.29 0.1764 0.3501
CELL_CYCLE 89 S 1.68 0.0550 0.2288 1.79 0.0123 0.0944 2.09 0.0151 0.0263
CELL_PROLIFERATION 72 Rosenwald et al. 1.89 0.0076 0.0672 0.81 0.7330 1.0000 1.43 0.0334 0.3203 1.75 0.0000 0.1239
DNA_DAMAGE_SIGNALING_PATHWAY 94 S 1.36 0.1264 0.5941 1.62 0.0165 0.1580 1.33 0.0853 0.3487
ECM_MEMBRANE_CELL-CELL_ADHESION 88 S 0.73 0.8029 0.9670 0.68 0.8980 0.9737 1.30 0.1113 0.4426 1.55 0.0345 0.2028
GENES_CONSTITUTING_THE_PI3_KINASE_PREDICTOR 92 Potti et al. 1.40 0.2090 0.5758 1.78 0.0043 0.0581 2.12 0.0127 0.0274
HEDGEHOG_SIGNALING_PATHWAY__KEGG 39 K 1.13 0.2937 0.9573 0.66 0.9426 1.0000 1.61 0.0446 0.1609 1.11 0.3176 1.0000
HYPOXIA_SIGNALING_PATHWAY 45 S 1.19 0.2416 0.7823 1.32 0.1068 0.4590 2.00 0.0000 0.0491 0.91 0.5791 1.0000
METABOLISM_OF_XENOBIOTICS_BY_CYTOCHROME_P450__KEGG 40 K 0.62 0.9030 1.0000 1.85 0.0250 0.0845
NITRIC_OXIDE 134 S 0.84 0.6558 1.0000 1.64 0.0075 0.1443
PPAR_SIGNALING_PATHWAY__KEGG 60 K 0.64 0.9509 0.9531 1.39 0.0390 1.0000 0.72 0.8947 1.0000
PROLIFERATION_SIGNATURE 50 Whitfield et al. 1.48 0.1637 0.4510 1.71 0.0104 0.0958 2.34 0.0000 0.0013
RECURRENCE_SCORE 16 Paik et al. 1.05 0.4041 0.7800 1.57 0.0271 0.1550 1.98 0.0041 0.0437 0.97 0.4733 1.0000
ROTTERDAM_SIGNATURE 62 Klijn et al. 1.47 0.0716 0.4331 0.96 0.5787 1.0000 1.67 0.0078 0.1143 0.95 0.5168 0.6004 1.10 0.3152 1.0000
SHEPARD_CELL_PROLIFERATION 194 Shepherd et al. 1.22 0.1274 0.7243 0.81 0.8165 0.9841 1.04 0.3695 0.7669 1.72 0.0000 0.1122
T-CELL_AND_B-CELL_ACTIVATION 53 S 1.37 0.1306 1.0000 1.74 0.0091 0.1148
TOLL-LIKE_RECEPTOR_SIGNALING_PATHWAY__KEGG 86 K 0.71 0.8741 0.9589 0.58 0.9752 0.9993 1.63 0.0234 0.1402
TOXICOLOGY_&_DRUG_RESISTANCE 70 S 0.84 0.7958 0.8865 1.33 0.0761 0.4825 1.37 0.0396 0.3300
TSP1_PATHWAY 7 S 0.73 0.8141 0.9825 0.94 0.5290 1.0000 1.50 0.0472 0.2300 0.51 0.9707 0.9810
TUMOR_METASTASIS 59 S 1.66 0.0303 0.2160 0.77 0.8696 1.0000 1.27 0.0860 0.4950 1.72 0.0028 0.1033
UNDERHILL_PROLIFERATION 13 Underhill et al. 1.55 0.0726 0.4131 1.58 0.0578 0.1611 1.68 0.0310 0.1229
VV_70GENE_SIGNATURE 70 van'tVeer et al. 1.58 0.0221 0.1876 1.10 0.3346 0.4765
NAME NES NES
III IV
N°
genesSource NES
VIIV VI
NES NES
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:
NOM FDR NOM FDR NOM FDR NOM FDR NOM FDR
p-val q-val p-val q-val p-val q-val p-val q-val p-val q-val
ANTIGEN_PROCESSING_AND_PRESENTATION__KEGG 69 K 1.39 0.0964 0.4616 0.81 0.7002 1.0000 0.99 0.4283 0.7587 2.09 0.0057 0.0071
APOPTOSIS 141 S 1.56 0.0229 0.4117 0.85 0.7555 1.0000 1.03 0.4075 0.7035 1.41 0.0433 0.2590
CELL_ADHESION_MOLECULES_(CAMS)_KEGG 89 K 1.52 0.0214 0.4111 0.75 0.7589 0.9690 2.10 0.0000 0.0128
CELL_PROLIFERATION 72 Rosenwald et al. 1.49 0.1680 0.3076 0.69 0.8787 1.0000 1.45 0.0231 0.4588 1.35 0.0708 0.2447
CHEMOKINE_LIGAND_RECEPTOR 90 S 1.21 0.2626 0.5539 0.90 0.5844 1.0000 0.86 0.6045 0.8052 1.84 0.0018 0.0298
DNA_DAMAGE_SIGNALING_PATHWAY 94 S 0.95 0.4833 0.5684 1.66 0.0108 0.2867 0.71 0.9220 0.8627
ECM_MEMBRANE_CELL-CELL_ADHESION 88 S 1.54 0.0122 0.4131 0.66 0.8863 1.0000 1.28 0.1232 0.4760 1.52 0.0422 0.1575
ECM_MEMBRANE_CELL-MATRIX_ADHESION 125 S 1.63 0.0236 0.3986 1.03 0.4220 0.7119 1.32 0.1049 0.2480 0.82 0.7348 1.0000
GENES_CONSTITUTING_THE_PI3_KINASE_PREDICTOR 92 Potti et al. 0.52 0.8686 0.9734 1.61 0.0124 0.2582 1.39 0.0942 0.2385
INFLAMMATORY_CYTOKINES_&_RECEPTORS 78 S 1.12 0.3911 0.4803 0.82 0.6498 1.0000 0.40 0.9870 1.0000 1.68 0.0128 0.0712
JAK___STAT_SIGNALING_PATHWAY 141 S 1.05 0.4246 0.5121 1.20 0.2677 1.0000 1.53 0.0123 0.1539
METALLOPROTEASES 24 S 1.04 0.4098 0.4891 1.20 0.2869 1.0000 1.10 0.3488 0.6847 1.73 0.0058 0.0525
NATURAL_KILLER_CELL_MEDIATED_CYTOTOXICITY__KEGG 108 K 1.14 0.3532 0.4975 0.83 0.7348 1.0000 0.52 0.9874 1.0000 1.90 0.0000 0.0394
NFKB_SIGNALING_PATHWAY 87 S 0.99 0.5016 0.5404 0.72 0.8838 1.0000 1.58 0.0152 0.1232
NITROGEN_METABOLISM__KEGG 23 K 1.50 0.0417 0.3513 0.63 0.9119 0.0000 0.96 0.5363 0.7662 1.11 0.3145 0.9110
P53_SIGNALING_PATHWAY 105 S 1.25 0.1684 0.5690 1.72 0.0071 0.2576 0.80 0.8172 0.7765
PROLIFERATION_SIGNATURE 50 Whitfield et al. 1.51 0.0204 0.4818 1.82 0.0214 0.0292
RIBOSOME_KEGG 75 K 0.73 0.7169 0.8399 1.57 0.0448 1.0000 0.73 0.6378 0.9765 1.11 0.2884 0.9723
ROTTERDAM_SIGNATURE 62 Klijn et al. 1.30 0.2053 0.5489 1.38 0.0494 0.5073 0.87 0.6940 0.7108 0.95 0.5925 1.0000
SHEPARD_NEG_REG_OF_CELL_PROLIFERATION 103 Shepard et al. 1.48 0.0447 0.4900 1.02 0.4226 0.5716
SIGNAL_TRANSDUCTION_IN_CANCER 85 S 1.60 0.0637 0.3786 0.97 0.4537 0.7801 1.51 0.0494 0.1601
T-CELL_AND_B-CELL_ACTIVATION 53 S 1.22 0.2838 0.5691 0.85 0.6352 1.0000 0.40 1.0000 0.9958 2.02 0.0000 0.0131
T_CELL_RECEPTOR_SIGNALING_PATHWAY__KEGG 84 K 0.85 0.6447 0.6757 0.66 0.9268 1.0000 0.73 0.8767 0.9914 1.87 0.0000 0.0274 0.71 0.8919 0.9952
TNF_L&R 19 S 1.79 0.0316 0.2337 1.06 0.4220 1.0000 1.10 0.3478 0.7029 1.60 0.0356 0.1154
TOLL-LIKE_RECEPTOR_SIGNALING_PATHWAY__KEGG 86 K 0.96 0.5562 0.5591 0.61 0.9650 0.0000 0.53 0.9821 1.0000 1.70 0.0070 0.0666
TUMOR_METASTASIS 59 S 1.70 0.0390 0.3097 0.75 0.8613 1.0000 0.87 0.6864 0.8389 1.73 0.0000 0.0565
TUMOR_NECROSIS_FACTOR 61 S 1.12 0.2978 0.4732 1.07 0.3750 1.0000 1.33 0.0987 0.5137 1.87 0.0000 0.0320 0.68 0.9056 0.9870
UNDERHILL_PROLIFERATION 13 Underhill et al. 1.17 0.3231 0.5186 1.74 0.0071 0.4294 1.62 0.0184 0.1049
IV V VI VII
NAMEN°
genesSource NES NES NES NES NES
III
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
OPN and MMP-9 in datasets III, V and VI.
Symbol Name OPN MMP9
ARHGEF1 Rho guanine nucleotide exchange factor (GEF) 1
BUB1 BUB1 budding uninhibited by benzimidazoles 1 homolog (yeast)
BUB1B BUB1 budding uninhibited by benzimidazoles 1 homolog beta (yeast)
BUB3 BUB3 budding uninhibited by benzimidazoles 3 homolog (yeast)
CDK6 Cyclin-dependent kinase 6
CDK7 Cyclin-dependent kinase 7
CKS1B CDC28 protein kinase regulatory subunit 1B
CKS2 CDC28 protein kinase regulatory subunit 2
CSF1R Colony stimulating factor 1 receptor, formerly McDonough feline sarcoma viral (v-fms) oncogene homolog
EGFR Epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian)
EHF Ets homologous factor
ELF5 E74-like factor 5 (ets domain transcription factor)
EMP2 In multiple clusters
EPHB4 EPH receptor B4
EVI5 Ecotropic viral integration site 5
FGF6 Fibroblast growth factor 6
FSCN1 Fascin homolog 1, actin-bundling protein (Strongylocentrotus purpuratus)
FZD3 Frizzled homolog 3 (Drosophila)
GAB1 GRB2-associated binding protein 1
GPC4 Glypican 4
GSPT1 G1 to S phase transition 1
HDGF Hepatoma-derived growth factor (high-mobility group protein 1-like)
HDGFRP3 Hepatoma-derived growth factor, related protein 3
IL1A Interleukin 1, alpha
IL1B Interleukin 1, beta
IL2RG Interleukin 2 receptor, gamma (severe combined immunodeficiency)
IL3 Interleukin 3 (colony-stimulating factor, multiple)
IL6 Interleukin 6 (interferon, beta 2)
IL6R Interleukin 6 receptor
ISG20 Interferon stimulated exonuclease gene 20kDa
KHDRBS1 KH domain containing, RNA binding, signal transduction associated 1
KIF2C Kinesin family member 2C
KITLG KIT ligand
KRT16 Keratin 16 (focal non-epidermolytic palmoplantar keratoderma)
LGI1 Leucine-rich, glioma inactivated 1
MAD1L1 MAD1 mitotic arrest deficient-like 1 (yeast)
MET Met proto-oncogene (hepatocyte growth factor receptor)
MIA Melanoma inhibitory activity
MNAT1 Menage a trois homolog 1, cyclin H assembly factor (Xenopus laevis)
MS4A1 Membrane-spanning 4-domains, subfamily A, member 1
MT3 Metallothionein 3
MTCP1 Mature T-cell proliferation 1
MYC Similar to ORF 114
NDP Norrie disease (pseudoglioma)
NR6A1 Nuclear receptor subfamily 6, group A, member 1
NUDC Nuclear distribution gene C homolog (A. nidulans)
PCNA Proliferating cell nuclear antigen
PDAP1 PDGFA associated protein 1
PDGFA Platelet-derived growth factor alpha polypeptide
PDZK1 PDZ domain containing 1
PIM2 Pim-2 oncogene
PRDX1 Peroxiredoxin 1
PRG4 Proteoglycan 4
PRL Prolactin
PTHLH Parathyroid hormone-like hormone
PYY Peptide YY
RBBP7 Retinoblastoma binding protein 7
RPS4X Ribosomal protein S4, X-linked
SFN Stratifin
SIPA1 Signal-induced proliferation-associated gene 1
SKP2 S-phase kinase-associated protein 2 (p45)
TACSTD2 Tumor-associated calcium signal transducer 2
TAL1 T-cell acute lymphocytic leukemia 1
TFDP1 Transcription factor Dp-1
TGFA Transforming growth factor, alpha
THPO Thrombopoietin (myeloproliferative leukemia virus oncogene ligand, megakaryocyte growth and development factor)
TM4SF1 Transmembrane 4 L six family member 1
TNFRSF9 Tumor necrosis factor receptor superfamily, member 9
TNFSF8 Tumor necrosis factor (ligand) superfamily, member 8
TNFSF9 Tumor necrosis factor (ligand) superfamily, member 9
TPX2 TPX2, microtubule-associated, homolog (Xenopus laevis)
ZFP36L2 Zinc finger protein 36, C3H type-like 2
Shaded areas indicate statistically significant enrichment
Supplemental Table 4b. List of genes from the GENES_CONSTITUTING_THE_PI3_KINASE_PREDICTOR
gene sets and their association with OPN and MMP-9 in datasets III, V and VI.
Symbol Name OPN MMP9
AKR7A3 Aldo-keto reductase family 7, member A3 (aflatoxin aldehyde reductase)
ANKRD32 Ankyrin repeat domain 32
ATAD2 ATPase family, AAA domain containing 2
BARD1 BRCA1 associated RING domain 1
BRD2 Bromodomain containing 2
CASP8AP2 CASP8 associated protein 2
CDC45L CDC45 cell division cycle 45-like (S. cerevisiae)
CDC25A Cell division cycle 25 homolog A (S. pombe)
CDC6 Cell division cycle 6 homolog (S. cerevisiae)
CDC7 Cell division cycle 7 homolog (S. cerevisiae)
CDCA5 Cell division cycle associated 5
CDCA7 Cell division cycle associated 7
CHEK1 CHK1 checkpoint homolog (S. pombe)
CSPG5 Chondroitin sulfate proteoglycan 5 (neuroglycan C)
CDT1 Chromatin licensing and DNA replication factor 1
CSE1L CSE1 chromosome segregation 1-like (yeast)
CCNE1 Cyclin E1
CCNE2 Cyclin E2
DDX10 DEAD (Asp-Glu-Ala-Asp) box polypeptide 10
DNMT1 DNA (cytosine-5-)-methyltransferase 1
DCLRE1B DNA cross-link repair 1B (PSO2 homolog, S. cerevisiae)
EGR1 Early growth response 1
EED Embryonic ectoderm development
FEN1 Flap structure-specific endonuclease 1
GPR27 G protein-coupled receptor 27
GAL Galanin prepropeptide
GEMIN4 Gem (nuclear organelle) associated protein 4
GMNN Geminin, DNA replication inhibitor
GADD45B Growth arrest and DNA-damage-inducible, beta
GAS2L1 Growth arrest-specific 2 like 1
H2AFX H2A histone family, member X
HSPA1A Heat shock 70kDa protein 1A
HSPA1B Heat shock 70kDa protein 1B
ID1 Inhibitor of DNA binding 1, dominant negative helix-loop-helix protein
ITPKC Inositol 1,4,5-trisphosphate 3-kinase C
IL17RB Interleukin 17 receptor B
IL17D Interleukin 17D
JUNB Jun B proto-oncogene
JUN Jun oncogene
JPH1 Junctophilin 1
LMNB1 Lamin B1
LMNB2 Lamin B2
LEF1 Lymphoid enhancer-binding factor 1
MAD2L1 MAD2 mitotic arrest deficient-like 1 (yeast)
MTHFD1 Methylenetetrahydrofolate dehydrogenase (NADP+ dependent)
MCM10 Minichromosome maintenance complex component 10
MCM2 Minichromosome maintenance complex component 2
MCM3 Minichromosome maintenance complex component 3
MCM4 Minichromosome maintenance complex component 4
MCM5 Minichromosome maintenance complex component 5
MCM6 Minichromosome maintenance complex component 6
MCM7 Minichromosome maintenance complex component 7
MSH2 MutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)
NASP Nuclear autoantigenic sperm protein (histone-binding)
NOL5A Nucleolar protein 5A (56kDa with KKE/D repeat)
PEX5 Peroxisomal biogenesis factor 5
PPAT Phosphoribosyl pyrophosphate amidotransferase
PRPS1 Phosphoribosyl pyrophosphate synthetase 1
KCTD12 Potassium channel tetramerisation domain containing 12
PRIM1 Primase, DNA, polypeptide 1 (49kDa)
PCNA Proliferating cell nuclear antigen
PRKRIR Protein-kinase, interferon-inducible double stranded RNA dependent inhibitor
PDXP Pyridoxal (pyridoxine, vitamin B6) phosphatase
RAD51 RAD51 homolog (RecA homolog, E. coli) (S. cerevisiae)
RHOB Ras homolog gene family, member B
RFC2 Replication factor C (activator 1) 2, 40kDa
RFC3 Replication factor C (activator 1) 3, 38kDa
RPA3 Replication protein A3, 14kDa
RPP25 Ribonuclease P/MRP 25kDa subunit
RRM2 Ribonucleotide reductase M2 polypeptide
RBM15 RNA binding motif protein 15
SLC25A15 Solute carrier family 25 (mitochondrial carrier; ornithine transporter) member 15
SLC25A19 Solute carrier family 25 (mitochondrial thiamine pyrophosphate carrier), member 19
SPEN Spen homolog, transcriptional regulator (Drosophila)
SLBP Stem-loop binding protein
SUPT16H Suppressor of Ty 16 homolog (S. cerevisiae)
SSX2IP Synovial sarcoma, X breakpoint 2 interacting protein
TAF5 TAF5 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 100kDa
TOP3A Topoisomerase (DNA) III alpha
TCF19 Transcription factor 19 (SC1)
TLE3 Transducin-like enhancer of split 3 (E(sp1) homolog, Drosophila)
TBRG4 Transforming growth factor beta regulator 4
TMEM18 Transmembrane protein 18
UBE2T Ubiquitin-conjugating enzyme E2T (putative)
UHRF1 Ubiquitin-like, containing PHD and RING finger domains, 1
UNG Uracil-DNA glycosylase
UMPS Uridine monophosphate synthetase
MYB V-myb myeloblastosis viral oncogene homolog (avian)
ZNF45 Zinc finger protein 45
ZNF473 Zinc finger protein 473
ZMYND19 Zinc finger, MYND-type containing 19
ZWINT ZW10 interactor antisense
Shaded areas indicate statistically significant enrichment
Supplemental Table 4c. List of genes from the PROLIFERATION_SIGNATURE gene sets and their association
with OPN and MMP-9 in datasets III, V and VI.
Symbol Name OPN MMP9
AURKB Aurora kinase B
BIRC5 Effector cell peptidase receptor 1
BUB1 BUB1 budding uninhibited by benzimidazoles 1 homolog (yeast)
CCNA2 Cyclin A2
CCNB1 Cyclin B1
CCNE1 Cyclin E1
CCNE2 Cyclin E2
CCNF Cyclin F
CDC20 Cell division cycle 20 homolog (S. cerevisiae)
CDC25C Cell division cycle 25 homolog C (S. pombe)
CDC6 Cell division cycle 6 homolog (S. cerevisiae)
CDC7 Cell division cycle 7 homolog (S. cerevisiae)
CDH3 Cadherin 3, type 1, P-cadherin (placental)
CENPE Centromere protein E, 312kDa
CENPF Centromere protein F, 350/400ka (mitosin)
CHEK1 CHK1 checkpoint homolog (S. pombe)
CKS2 CDC28 protein kinase regulatory subunit 2
CTPS CTP synthase
DDX11 DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 11 (CHL1-like helicase homolog, S. cerevisiae)
DHFR Dihydrofolate Reductase
DNMT1 DNA (cytosine-5-)-methyltransferase 1
E2F3 E2F transcription factor 3
EGFR Epidermal growth factor receptor (erythroblastic leukemia viral (v-erb-b) oncogene homolog, avian)
ERBB2 V-erb-b2 erythroblastic leukemia viral oncogene homolog 2, neuro/glioblastoma derived oncogene homolog (avian)
EXOSC9 Exosome component 9
FEN1 Flap structure-specific endonuclease 1
KRT5 Keratin 5 (epidermolysis bullosa simplex, Dowling-Meara/Kobner/Weber-Cockayne types)
MAD2L1 MAD2 mitotic arrest deficient-like 1 (yeast)
MAPK13 Mitogen-activated protein kinase 13
MCM3 Minichromosome maintenance complex component 3
MCM4 Minichromosome maintenance complex component 4
MCM5 Minichromosome maintenance complex component 5
MCM6 Minichromosome maintenance complex component 6
MKI67 Antigen identified by monoclonal antibody Ki-67
MYB V-myb myeloblastosis viral oncogene homolog (avian)
NASP Nuclear autoantigenic sperm protein (histone-binding)
ORC1L Origin recognition complex, subunit 1-like (yeast)
PCNA Proliferating cell nuclear antigen
PKMYT1 Protein kinase, membrane associated tyrosine/threonine 1
PLK1 Polo-like kinase 1 (Drosophila)
PRIM1 Primase, DNA, polypeptide 1 (49kDa)
PTTG1 Pituitary tumor-transforming 1
RFC1 Replication factor C (activator 1) 1, 145kDa
RRM1 Ribonucleotide reductase M1
RRM2 Ribonucleotide reductase M2 polypeptide
TIMP1 TIMP metallopeptidase inhibitor 1
TOP2A Topoisomerase (DNA) II alpha 170kDa
TP53 Tumor protein p53
TYMS Thymidylate synthetase
UNG Uracil-DNA glycosylase
Shaded areas indicate statistically significant enrichment
Supplemental Table 4d. List of genes from the TUMOR_METASTASIS gene sets and their association with
OPN and MMP-9 in datasets III, V and VI.
Symbol Name OPN MMP9
APC Adenomatous polyposis coli
BAI1 Brain-specific angiogenesis inhibitor 1
BRMS1 Breast cancer metastasis suppressor 1
CAV1 Caveolin 1, caveolae protein, 22kDa
CD44 CD44 molecule (Indian blood group)
CDK4 Cyclin-dependent kinase 4
CDKN2A Cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)
CHD4 Chromodomain helicase DNA binding protein 4
CST7 Cystatin F (leukocystatin)
CTNNA1 Catenin (cadherin-associated protein), alpha 1, 102kDa
CTNNB1 Catenin (cadherin-associated protein), beta 1, 88kDa
CXCL12 Chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1)
CXCR4 Chemokine (C-X-C motif) receptor 4
DENR Density-regulated protein
ETV4 Ets variant gene 4 (E1A enhancer binding protein, E1AF)
ETV6 Ets variant gene 6 (TEL oncogene)
EWSR1 Ewing sarcoma breakpoint region 1
FGFR4 Fibroblast growth factor receptor 4
FLT4 Fms-related tyrosine kinase 4
FN1 Fibronectin 1
GNRH1 Gonadotropin-releasing hormone 1 (luteinizing-releasing hormone)
GNRH2 Gonadotropin-releasing hormone 2
GZMA Granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated serine esterase 3)
HDAC1 Histone deacetylase 1
HPSE Heparanase
HRAS V-Ha-ras Harvey rat sarcoma viral oncogene homolog
HTATIP2 HIV-1 Tat interactive protein 2, 30kDa
IL18 Interleukin 18 (interferon-gamma-inducing factor)
IL1B Interleukin 1, beta
IL8RB Interleukin 8 receptor, beta
ITGA7 Integrin alpha 7
KISS1 KiSS-1 metastasis-suppressor
MDM2 Mdm2 p53 binding protein homolog (mouse)
MET Met proto-oncogene (hepatocyte growth factor receptor)
METAP2 Methionyl aminopeptidase 2
MMP10 Matrix metallopeptidase 10 (stromelysin 2)
MMP11 Matrix metallopeptidase 11 (stromelysin 3)
MMP13 Matrix metallopeptidase 13 (collagenase 3)
MMP7 Matrix metallopeptidase 7 (matrilysin, uterine)
MMP9 Matrix metallopeptidase 9 (gelatinase B, 92kDa gelatinase, 92kDa type IV collagenase)
MTA1 Metastasis associated 1
MTA2 Metastasis associated 1 family, member 2
MTSS1 Metastasis suppressor 1
MYB V-myb myeloblastosis viral oncogene homolog (avian)
MYC Similar to ORF 114
MYCL1 V-myc myelocytomatosis viral oncogene homolog 1, lung carcinoma derived (avian)
NF2 Neurofibromin 2 (merlin)
NME1 Non-metastatic cells 1, protein (NM23A) expressed in
NME4 Non-metastatic cells 4, protein expressed in
NR4A3 Nuclear receptor subfamily 4, group A, member 3
PCOLN3 Chromatin modifying protein 1A
PLAUR Plasminogen activator, urokinase receptor
PTHLH Parathyroid hormone-like hormone
PTP4A3 Protein tyrosine phosphatase type IVA, member 3
RB1 Retinoblastoma 1 (including osteosarcoma)
RHOC Ras homolog gene family, member C
RORB RAR-related orphan receptor B
S100A4 S100 calcium binding protein A4
SERPINB5 Serpin peptidase inhibitor, clade B (ovalbumin), member 5
Shaded areas indicate statistically significant enrichment