identificazione di pathways molecolari associati alla...
TRANSCRIPT
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Iden
tifica
zion
e di
pat
hway
smolec
olar
i as
sociat
i alla
resist
enza
all’im
atinib
nella
leu
cemia m
ieloid
ecr
onica
med
iant
e la t
ecno
logia
del micro
arra
y.
Dal d
esign
all’a
nalis
i de
i da
ti
Rosa
nna
Mar
tine
lli P
h.D
.D
ipar
tim
ento
di B
ioch
imic
a e
Biot
ecno
logi
e M
edic
heU
nive
rsit
à de
gli S
tudi
di N
apol
i “Fe
deri
co I
I”CE
INGE
-Bio
tecn
olog
ieA
vanz
ate
ICA
R-CN
R 18
dic
embr
e20
07
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
THE
FIRS
T RO
BOT
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
MIC
ROARR
AY
:NOT
JUST
FOR
GENOM
ICS
Alth
ough
the
sample
type
s,
dete
ction
met
hods
and
numbe
rof
sam
ples
chan
ge,
the
biolog
ical
assa
ysth
emse
lves
trad
itiona
llyha
vere
maine
d “GRI
ND A
ND B
IND”
stud
ying
the
bind
ing
even
tsof
va
riou
sbi
omolec
ules
toob
tain
info
rmat
ions
abou
tbi
olog
yof
a c
ell.
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
SAM
PLE
TY
PE
INT
ER
AC
TIO
NA
PP
LIC
AT
ION
S
Olig
onu
cleo
tide
DN
A-D
NA
, DN
A-R
NA
Evo
luti
on,
Ge
ne E
xpre
ssio
n, G
eno
typi
ng, M
appi
ng, S
NP
Ma
ppin
g,
(DN
A,
RN
A)
RN
A-R
NA
, DN
A-P
rote
inSN
P D
etec
tion
, Str
uctu
re-f
unct
ion,
Tw
o hy
brid
ana
lysi
sR
NA
-Pro
tein
PC
R P
rodu
cts
DN
A-D
NA
, DN
A-R
NA
Evo
luti
on,
Ge
ne E
xpre
ssio
n, G
eno
typi
ng, M
appi
ng, S
NP
Det
ecti
on,
DN
A-P
rote
inSt
ruct
ure
-fu
ncti
on,T
wo
hyb
rid
ana
lysi
s
BA
Cs
DN
A-D
NA
, DN
A-R
NA
Con
tig
asse
mbl
y, E
volu
tion
, G
enot
ypin
g, M
app
ing,
Sys
tem
ic A
naly
sis,
D
NA
-Pro
tein
Com
para
tive
Ge
nom
ic H
ybri
diza
tion
Pro
tein
Pro
tein
-DN
A, P
rote
in-R
NA
Dru
g D
isco
very
, Ep
itop
e M
appi
ng, E
volu
tion
, Gen
e E
xpre
ssio
n, G
eno
t yP
rote
in-P
rote
in,
Pro
tein
-Rec
ept
orP
rote
om
ics,
Po
st-T
ran
slat
iona
l Ana
lysi
s, S
tru
ctur
e-F
unct
ion
, P
rote
in-S
mal
l Mol
ecu
leT
wo
Hyb
rid
An
alys
is
Ant
ibod
ies
Ant
ibo
dy-A
ntig
en,
Epit
ope
Map
ping
, Evo
luti
on, G
ene
Exp
ress
ion,
Gen
oty
ping
, A
ntib
ody
-RN
AP
rote
om
ics,
Po
st-T
ran
slat
iona
l Ana
lysi
s, S
tru
ctur
e-F
unct
ion
,A
ntib
ody
-DN
A,
Ant
ibo
dy-C
ell
Surf
ace
Ant
ibo
dy-O
rgan
elle
Enzy
mes
Enzy
me
s-Su
bstr
ate
Kin
eti
cs, S
ubs
tra
te S
pec
ific
ity,
In
hibi
tor
An
alys
isEn
zym
es-
Effe
cto
rEn
zym
es-
Inh
ibit
or
Car
boh
ydra
tes
Suga
r-P
rote
in, S
uga
r-A
nti
body
Do
ckin
g, S
igna
ling
Suga
r-R
ecep
tor
Smal
l Mo
lecu
leSm
all
Mol
ecu
le-P
rote
inB
ind
ing
Kin
etic
s, D
rug
Dis
cove
ry
EX S
ITU M
ICRO
ARR
AY
APP
LICA
TIONS
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Geno
mic
App
licat
ions
From
Agilent
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
cDNA M
icro
arra
ys
Adv
anta
ges
Disad
vant
ages
Incr
ease
d de
tect
ion
sens
itivity
due
to lon
ger
sequ
ence
sCr
oss-
hybr
idisat
ion
can
be a
pro
blem
Aff
orda
ble
Maint
aining
clone
s an
d PC
R am
plificat
ion
is lab
our-
inte
nsive
Olig
onuc
leot
ide
arra
ys (in g
ener
al)
Adv
anta
ges
Disad
vant
ages
Highe
r sp
ecificity
Dec
reas
ed s
ensitivity
due
to
shor
ter
sequ
ence
s (lowe
r se
nsitivity
compe
nsat
ed b
y us
e of
multiple
prob
es)
Mor
e un
ifor
m m
elting
tem
pera
ture
sEx
pens
ive
to d
esign
and
man
ufac
ture
Det
ection
of
SNP
and
splic
e va
rian
tsHighe
r un
ifor
mity
of s
pots
(con
trolled
amou
nt o
f mat
erial pe
r sp
ot)
Aff
ymet
rix
and
Agilent
Olig
onuc
leot
ide
arra
ys
Aff
ymet
rix
Only
1-co
lour
is
offe
red
Dec
reas
ed s
ensitivity
due
to
shor
ter
sequ
ence
s (2
5-mer
); h
owev
er, lowe
r se
nsitivity
compe
nsat
ed b
y th
e fa
ct t
hat
multiple
oligos
repr
esen
t ea
ch g
ene
Add
itiona
l eq
uipm
ent
(spe
cialised
fluidics
sta
tion
and
Aff
ymet
rix-
spec
ific s
cann
er) re
quired
Agilent
Off
ers
both
1-
and
2-co
lour
sys
tems
Long
er 6
0-mer
s ar
e mor
e to
lera
nt o
f se
quen
ce m
ismat
ches
and
thu
s ar
e mor
e su
itab
le f
or a
nalysis
of h
ighly
polymor
phic r
egions
Agilent
1-c
olou
r ve
rsus
2-c
olou
r•1
-colou
r allows
for
exp
erim
enta
l de
sign
to
chan
ge t
hrou
ghou
t pr
ojec
t –
good
for
pro
ject
s th
at w
ill t
ake
plac
e ov
er
a long
period
of
time
with
an
unkn
own
numbe
r of
sam
ples
•2
-colou
r is a
mor
e di
rect
com
pariso
n of
two
sam
ples
Gene
Exp
ress
ion:
Each
Plat
form
has
its
own
Adv
anta
ges
and
Disad
vant
ages
,.
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
ORI
GINAL
MIC
ROARR
AY
FLOW
-CHART
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
CO
MP
UTE
R
CO
MP
UTE
R
WO
RK
STA
TIO
NW
OR
KS
TATI
ON
FLU
IDIC
SFL
UID
ICS
STA
TIO
NS
TATI
ON
HY
BR
IDIZ
ATI
ON
HY
BR
IDIZ
ATI
ON
OV
ENO
VEN
SC
AN
NER
S
CA
NN
ER
SY
STE
MS
YS
TEM
PH
OTO
LITO
GR
AP
HY
Gen
eCh
ip
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Gene
Chip
® E
xpre
ssio
n A
rray
Des
ign
Tran
scrip
t5´
PM MM
3´
Mul
tiple
ol
igo
prob
es
600
nt
Prob
e se
t
Prob
e pa
ir
Feat
ures
or
prob
e ce
lls
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
IMPO
RTANT
STEP
S I
N M
ICRO
ARR
AY
EXPE
RIM
ENTS
EXPE
RIM
ENTA
L DES
IGN
Goal(s) fo
rmulat
ion
Reso
urce
salloca
tion
Expe
rimen
talun
itde
finition
Stat
istica
lpo
wer
and
sam
pling
Stat
istica
lde
sign
validat
ion
HYB
RIDIZ
ATI
ON
Prob
esan
d slid
estr
eatm
ent
Targ
et lab
eling
QC
Hyb
ridi
zation
Was
hing
Dry
ing
TARG
ETS C
OLL
ECTI
ON
Select
ion
Char
acte
riza
tion
Purifica
tion
QC
DATA
TRA
NSF
ORM
ATI
ON
Imag
eac
quisition
Sign
alqu
antifica
tion
Back
grou
nd s
ubtr
action
Flag
Replicat
esNor
malizat
ion
Stat
istica
lev
alua
tion
KNOW
LEDGE
Clus
tering
clas
sifica
tion
Net
work
disco
very
Inte
grat
ion
in t
oa
biolog
ical
syst
ems
Alter
native
tec
hnolog
yco
nfirmat
ion
Ros
anna
Mar
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lli P
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Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Micro
Arr
ays
Flow
-Cha
rt
•RNA e
xtra
ction
•RNA q
ualit
ych
eck
•Lab
eling
stra
tegies
•Hyb
ridi
zation
•Imag
eAcq
uisition
•Dat
a Ana
lysis
Ros
anna
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tine
lli P
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Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Sample
Prep
arat
ion
and
QC
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Labe
lling
Nuc
leic A
cid
Reve
rse
tran
script
ion
and
Amino-
allylC
oupling
of R
NA
Prep
arat
ion
of F
luor
esce
nt c
DNA
Prob
e fr
om H
uman
mRN
A (a
lter
nate
pro
toco
l)
Mod
ified
Eber
wine
(“ANTI
SENSE
”) R
NA
Amplificat
ion
Prot
ocol
Roun
d A/
B DN
A Am
pifica
tion
Prot
ocol
Ros
anna
Mar
tine
lli P
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arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Hyb
ridi
zation
Ros
anna
Mar
tine
lli P
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arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
The
Agilent
Micro
arra
y Sc
anne
r.
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anna
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lli P
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arti
men
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Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Gene
exp
ress
ion
analys
isof
KCL
22 c
elllin
esfo
rth
e id
entifica
tion
of m
olec
ular
mec
hanism
sas
sociat
edto
imat
inib
resist
ance
Ana
lysis
of 2
2.00
0 hu
man
gene
sus
ing
60-m
er
oligon
ucleot
ides
(Agilent
) sint
hetize
don
glass
slid
es
Cell
lines
compa
riso
nan
d Tim
e Co
urse
For
each
expe
rimen
tsw
ap o
f dy
es
Imag
eac
quisition
with
the
Agilent
Sca
nner
Dat
a Ana
lysis
perf
ormed
with
Gene
Spring
, Ba
belomics
and
GO T
ree
Mac
hine
Ros
anna
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Bio
chim
ica
e B
iote
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ogie
Med
iche
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GE
Bio
tecn
olog
ie A
vanz
ate
Chro
nic
mye
loid
leu
kemia
Chro
nic
mye
loid
leuk
emia (C
ML)
is a
clon
al
diso
rder
of
th
e plur
ipot
ent
hemop
oiet
ic
stem
ce
ll,
in
which
a re
cipr
ocal
tran
sloc
ation
t(9;
22)(q3
4;q1
1)
form
s a
Phila
delphia
(Ph)
chr
omos
ome
and
crea
tes
a no
vel
fusion
ge
ne,
bcr–
abl.
Its
corr
espo
nding
prot
ein
has
a co
nstitu
tive
ly
activa
ted
tyro
sine
kinas
e th
at is
cent
ral to
th
e pa
thog
enes
is o
f CM
L.
Ros
anna
Mar
tine
lli P
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arti
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Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Imat
inib
clinical
effe
cton
chr
onic
mye
loge
nous
leuk
emia
Imat
inib
(for
mal
lyS
TI5
71
)ha
sbe
enre
port
edto
have
a sign
ifican
tclinical
effe
cton
chr
onic
mye
loge
nous
leuk
emia
(CM
L) in blas
tcr
isis
aswe
llas
in th
e ch
ronic
phas
e
Imat
inib
mes
ylat
e is
a se
lect
ive
BCR–
ABL
pr
otein
tyro
sine
kinas
e inhibi
tor
agains
t:
ABL
onc
opro
teins
(c-A
BL, BC
R-ABL
, ET
V1-A
BL),
c-KI
T
Plat
elet
-der
ived
gro
wth
fact
or r
ecep
tor
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Mec
hanism
of t
he d
rug
imat
inib
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Man
ypa
tien
tsin b
last
crisis
who
are
being
trea
ted
with
imat
inib
relaps
eat
a r
elat
ively
early
time,
su
gges
ting
that
leuk
emia
cells
tend
toac
quire
resist
ance
toim
atinib
easily
in b
last
crisis.
Dru
gre
sist
ance
isa
maj
or p
roblem
for
CML
patien
tsin b
last
crisis
who
are
being
trea
ted
with
imat
inib
.
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Imat
inib
res
ista
nce
mec
hanism
s
Intr
insic
resist
ance
to
imat
inib
src-
kina
se L
YNCo
nstitu
tive
nuc
lear
fac
tor
(NF)
-B a
ctivat
ion
Seco
ndar
y or
acq
uire
d re
sist
ance
Mut
ations
in
the
BCR–
ABL
dom
ain
Ove
rexp
ress
ion
of B
CR–A
BL o
ncop
rote
in
Neith
erov
erex
pres
sion
nor
mut
ations
of B
CR/A
BL h
ave
been
foun
din s
ome
imat
inib
-res
ista
ntce
lllin
esan
d pa
tien
ts
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
KCL2
2 an
d KC
L22R
CellLine
s
KCL2
2 is
a Ph
ilade
lphia
chro
mos
ome-
positive
cell
line
esta
blishe
dfr
ompe
riph
eral
bloo
dof
a
patien
twi
thCM
L in b
last
crisis
To
gene
rate
imat
inib
-res
ista
ntclon
es,
KCL2
2 ce
llswe
retr
eate
dwi
thst
ep-w
ise
incr
easing
conc
entr
ations
of
imat
inib
(0.1
–1.0
µM
)
The
IC5
0 va
lue
of imat
inib
for
KCL2
2/SR
isab
out
11.6
-fo
ld h
ighe
rth
anth
atto
KCL2
2 indica
ting
a sign
ifican
tre
sist
ance
toim
atinib
No
mut
ation
in th
e BC
R/ABL
ge
ne an
d no
incr
ease
in
BCR/
ABL
pro
tein
and
P-gp
leve
lswe
reob
serv
ed
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Gene
exp
ress
ion
analys
isof
KCL
22 c
elllin
esfo
rth
e id
entifica
tion
of m
olec
ular
mec
hanism
sas
sociat
edto
imat
inib
resist
ance
Ana
lysis
of 2
2.00
0 hu
man
gene
sus
ing
60-m
er
oligon
ucleot
ides
(Agilent
) sint
hetize
don
glass
slid
es
Cell
lines
compa
riso
nan
d Tim
e Co
urse
For
each
expe
rimen
tsw
ap o
f dy
es
Imag
eac
quisition
with
the
Agilent
Sca
nner
Dat
a Ana
lysis
perf
ormed
with
Gene
Spring
, Ba
belomics
and
GO T
ree
Mac
hine
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Gene
Spring
Dat
a Ana
lysis
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Gene
Spring
dat
a no
rmalizat
ion
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Gene
Spring
Dat
a Pr
oces
sing
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Gene
Spring
Sta
tist
ical
Ana
lysis
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Gene
Sor
ting
& I
nter
pret
atio
n
Gene
Ont
olog
yth
e G
O p
roje
ct h
asde
velo
ped
thre
est
ruct
ured
cont
rolle
dvo
cabu
larie
s(o
ntol
ogie
s) t
hat
desc
ribe
gene
pr
oduc
tsin
ter
ms
of t
heir
asso
ciat
ed
Biolog
ical P
roce
ssM
olec
ular
Fun
ction
Cellu
lar
Path
ways
KEGG
Pat
hway
sis
a co
llect
ion
of
man
ually
draw
npa
thwa
ym
aps
repr
esen
ting
know
ledg
eon
th
e m
olec
ular
inte
ract
ion
and
reac
tion
netw
orks
for:
Met
abolism
Gene
tic
info
rmat
ion
Enviro
men
talIn
form
ation
Cellu
lar
Proc
ess
Hum
andise
ases
Dru
gDev
elop
men
t
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Gene
Ont
olog
y
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
KCL2
2 Ti
me
Cour
se
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Ros
anna
Mar
tine
lli P
h.D
. Dip
arti
men
todi
Bio
chim
ica
e B
iote
cnol
ogie
Med
iche
-C
EIN
GE
Bio
tecn
olog
ie A
vanz
ate
Ack
nowl
edge
men
ts
Dot
t.ss
aTon
ia B
uono
mo
Dot
t.ss
aVe
ra R
ober
tiPr
of.
Fabr
izio P
ane
Sig.
Vitt
orio L
ucigna
no
Prof
.Fr
ance
sco
Salvat
ore