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Dynamic modularity of host protein interaction networks in Salmonella Typhi infection.
[typhoid]
Salmonella
Typhi
is
a
human-
restricted
pathogen
,
which
causes
typhoid
fever
and
remains
a
global
health
problem
in
the
developing
countries
.
Although
previously
reported
host
expression
datasets
had
identified
putative
biomarkers
and
therapeutic
targets
of
typhoid
fever
,
the
underlying
molecular
mechanism
of
pathogenesis
remains
incompletely
understood
.
We
used
five
gene
expression
datasets
of
human
peripheral
blood
from
patients
suffering
from
S
.
Typhi
or
other
bacteremic
infections
or
non-infectious
disease
like
leukemia
.
The
expression
datasets
were
merged
into
human
protein
interaction
network
(
PIN
)
and
the
expression
correlation
between
the
hubs
and
their
interacting
proteins
was
measured
by
calculating
Pearson
Correlation
Coefficient
(
PCC
)
values
.
The
differences
in
the
average
PCC
for
each
hub
between
the
disease
states
and
their
respective
controls
were
calculated
for
studied
datasets
.
The
individual
hubs
and
their
interactors
with
expression
,
PCC
and
average
PCC
values
were
treated
as
dynamic
subnetworks
.
The
hubs
that
showed
unique
trends
of
alterations
specific
to
S
.
Typhi
infection
were
identified
.
We
identified
S
.
Typhi
infection-
specific
dynamic
subnetworks
of
the
host
,
which
involve
81
hubs
and
1343
interactions
.
The
major
enriched
GO
biological
process
terms
in
the
identified
subnetworks
were
regulation
of
apoptosis
and
biological
adhesions
,
while
the
enriched
pathways
include
cytokine
signalling
in
the
immune
system
and
downstream
TCR
signalling
.
The
dynamic
nature
of
the
hubs
CCR
1
,
IRS
2
and
PRKCA
with
their
interactors
was
studied
in
detail
.
The
difference
in
the
dynamics
of
the
subnetworks
specific
to
S
.
Typhi
infection
suggests
a
potential
molecular
model
of
typhoid
fever
.
Hubs
and
their
interactors
of
the
S
.
Typhi
infection-
specific
dynamic
subnetworks
carrying
distinct
PCC
values
compared
with
the
non-
typhoid
and
other
disease
conditions
reveal
new
insight
into
the
pathogenesis
of
S
.
Typhi
.
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"human peripheral blood"
symptom
severe combined immunodeficiency
typhoid
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