Abstract
Background
Changing
cell-type
proportions
can
confound
studies
of
differential
gene
expression
or
DNA
methylation
(DNAm)
from
peripheral
blood
mononuclear
cells
(PBMCs).
We
examined
how
derived
the
transcriptome
versus
methylome
influence
estimates
differentially
expressed
genes
(DEGs)
and
methylated
positions
(DMPs).
Methods
Transcriptome
DNAm
data
were
obtained
PBMC
RNA
Kenyan
children
(
n
=
8)
before,
during,
6
weeks
following
uncomplicated
malaria.
DEGs
DMPs
between
time
points
detected
using
adjusted
modeling
with
Cibersortx
IDOL,
respectively.
Results
Most
major
cell
types
principal
components
had
moderate
to
high
correlation
two
deconvolution
methods
r
0.60–0.96).
Estimates
largely
unaffected
by
method,
greatest
discrepancy
in
estimation
neutrophils.
Conclusion
Variation
is
captured
similarly
both
transcriptomic
for
most
types.
Cancer Research,
Год журнала:
2024,
Номер
84(11), С. 1898 - 1914
Опубликована: Март 19, 2024
Abstract
Tobacco
use
is
a
major
modifiable
risk
factor
for
adverse
health
outcomes,
including
cancer,
and
elicits
profound
epigenetic
changes
thought
to
be
associated
with
long-term
cancer
risk.
While
electronic
cigarettes
(e-cigarettes)
have
been
advocated
as
harm
reduction
alternatives
tobacco
products,
recent
studies
revealed
potential
detrimental
effects,
highlighting
the
urgent
need
further
research
into
molecular
impacts
of
e-cigarettes.
Here,
we
applied
computational
deconvolution
methods
dissect
cell-
tissue-specific
effects
or
e-cigarette
on
DNA
methylation
(DNAme)
in
over
3,500
buccal/saliva,
cervical,
blood
samples,
spanning
epithelial
immune
cells
at
directly
indirectly
exposed
sites.
The
535
identified
smoking-related
DNAme
loci
[cytosine-phosphate-guanine
sites
(CpG)]
clustered
four
functional
groups,
detoxification
growth
signaling,
based
cell
type
anatomic
site.
Loci
hypermethylated
buccal
smokers
NOTCH1/RUNX3/growth
receptor
signaling
also
exhibited
elevated
tissue
progressing
lung
carcinoma
situ
lesions,
hypermethylation
these
predicted
development
samples
collected
from
up
22
years
prior
diagnosis,
suggesting
role
driving
carcinogenesis.
Alarmingly,
CpGs
were
users
limited
smoking
history.
This
study
sheds
light
type–specific
landscape
induced
by
products.
Significance:
both
e-cigarettes
exposure-specific
that
are
predictive
carcinogenesis,
caution
when
broadly
recommending
aids
cessation.
ABSTRACT
Alzheimer's
disease
(AD)
is
a
leading
cause
of
dementia,
but
the
pathogenesis
mechanism
still
elusive.
Advances
in
proteomics
have
uncovered
key
molecular
mechanisms
underlying
AD,
revealing
complex
network
dysregulated
pathways,
including
amyloid
metabolism,
tau
pathology,
apolipoprotein
E
(APOE),
protein
degradation,
neuroinflammation,
RNA
splicing,
metabolic
dysregulation,
and
cognitive
resilience.
This
review
examines
recent
proteomic
findings
from
AD
brain
tissues
biological
fluids,
highlighting
potential
biomarkers
therapeutic
targets.
By
examining
landscape
them,
we
aim
to
deepen
our
understanding
support
developing
precision
medicine
strategies
for
more
effective
interventions.
Due
to
interindividual
variation
in
the
cellular
composition
of
human
cortex,
it
is
essential
that
covariates
capture
these
differences
are
included
epigenome-wide
association
studies
using
bulk
tissue.
As
experimentally
derived
cell
counts
often
unavailable,
computational
solutions
have
been
adopted
estimate
proportion
different
types
DNA
methylation
data.
Here,
we
validate
and
profile
use
an
expanded
reference
dataset
incorporating
two
neuronal
three
glial
subtypes
for
quantifying
cortex.
Psychosomatic Medicine,
Год журнала:
2024,
Номер
86(3), С. 137 - 145
Опубликована: Янв. 10, 2024
ABSTRACT
Objective
Psychosocial
stressors
have
been
linked
with
accelerated
biological
aging
in
adults;
however,
few
studies
examined
across
the
life
course
relation
to
aging.
Methods
In
359
individuals
(57%
White,
34%
Black)
from
Child
Health
and
Development
Studies
Disparities
study,
economic
(income,
education,
financial
strain),
social
(parent-child
relations,
caretaker
responsibilities)
traumatic
(death
of
a
sibling
or
child,
violence
exposure)
were
assessed
at
multiple
time
points
(birth
ages
9,
15,
50
years).
Experiences
major
discrimination
age
50.
Life
period
stress
scores
then
as
childhood
(birth–age
15
years)
adulthood
(age
At
years,
participants
provided
blood
samples,
DNA
methylation
was
EPIC
BeadChip.
Epigenetic
estimated
using
six
epigenetic
clocks
(Horvath,
Hannum,
Skin
Blood
age,
PhenoAge,
GrimAge,
Dunedin
Pace
Aging).
Age
acceleration
determined
residuals
regressing
chronologic
on
each
metrics.
Telomere
length
quantitative
polymerase
chain
reaction–based
methods.
Results
linear
regression
models
adjusted
for
race
gender,
total
stress,
adult
independently
predicted
based
GrimAge
faster
pace
DunedinPace.
Associations
attenuated
after
adjusting
smoking
status.
sex-stratified
analyses,
greater
associated
among
women
but
not
men.
No
associations
noted
telomere
length.
Conclusions
We
found
that
cumulative
differences
by
sex
(e.g.,
women).
Further
research
this
association
large
diverse
samples
is
needed.
Clinical Epigenetics,
Год журнала:
2024,
Номер
16(1)
Опубликована: Май 27, 2024
Abstract
Background
Methylation
of
serotonin-related
genes
has
been
proposed
as
a
plausible
gene-by-environment
link
which
may
mediate
environmental
stress,
depressive
and
anxiety
symptoms.
DNA
methylation
is
often
measured
in
blood
cells,
but
little
known
about
the
association
between
this
peripheral
epigenetic
modification
brain
serotonergic
architecture.
Here,
we
evaluated
whole-blood-derived
four
CpG
sites
serotonin
transporter
(
SLC6A4
)
six
tryptophan
hydroxylase
2
TPH2
gene
in-vivo
levels
(5-HTT)
4
receptor
(5-HT
cohort
healthy
individuals
N
=
254)
and,
for
5-HT
4,
unmedicated
patients
with
depression
90).
To
do
so,
quantified
/
using
bisulfite
pyrosequencing
estimated
5-HTT
positron
emission
tomography.
In
addition,
explored
measures
early
life
recent
symptoms
on
297
individuals.
Results
We
found
no
statistically
significant
markers
neurotransmission
or
although
CpG2
(chr17:30,236,083)
was
marginally
associated
parental
bonding
inventory
overprotection
score
cohort,
statistical
significance
did
not
remain
after
accounting
cell
heterogeneity.
Conclusions
suggest
that
findings
context
features
should
be
interpreted
caution.
More
studies
are
needed
to
rule
out
role
biomarkers
