Clinical Epigenetics,
Год журнала:
2024,
Номер
16(1)
Опубликована: Ноя. 18, 2024
DNA
methylation
is
a
critical
regulatory
mechanism
of
gene
expression,
influencing
various
human
diseases
and
traits.
While
traditional
expression
quantitative
trait
loci
(eQTL)
studies
have
helped
elucidate
the
genetic
regulation
there
growing
need
to
explore
environmental
influences
on
expression.
Existing
methods
such
as
PrediXcan
FUSION
focus
genotype-based
associations
but
overlook
impact
factors.
To
address
this
gap,
we
present
MOSES
(methylation-based
association),
novel
approach
that
utilizes
identify
environmentally
regulated
genes
associated
with
traits
or
without
relying
measured
involves
training,
imputation,
association
testing.
It
employs
elastic-net
penalized
regression
models
estimate
influence
CpGs
SNPs
(if
available)
We
developed
compared
four
versions
incorporating
different
data:
(1)
cis-DNA
within
1
Mb
promoter
regions,
(2)
both
cis-SNPs
cis-CpGs,
3)
cis-
part
trans-
(±5Mb
away)
from
regions),
4)
long-range
(±10
regions.
Our
analysis
using
nasal
epithelium
white
blood
cell
data
Epigenetic
Variation
Childhood
Asthma
in
Puerto
Ricans
(EVA-PR)
study
demonstrated
MOSES,
particularly
version
(MOSES-DNAm
10
M),
significantly
outperformed
existing
like
PrediXcan,
MethylXcan,
Biomethyl
predicting
MOSES-DNAm
M
identified
more
differentially
expressed
(DEGs)
atopic
asthma,
those
involved
immune
pathways,
highlighting
its
superior
performance
uncovering
genes.
Further
application
lung
tissue
idiopathic
pulmonary
fibrosis
(IPF)
patients
confirmed
robustness
versatility
across
tissues.
represents
an
innovative
advancement
studies,
leveraging
capture
factors
By
CpGs,
provides
predictive
accuracy
capabilities
methods.
This
offers
valuable
insights
into
complex
interplay
between
genetics
environment,
enhancing
our
understanding
disease
mechanisms
potentially
guiding
therapeutic
strategies.
The
user-friendly
R
package
publicly
available
advance
diseases,
including
immune-related
conditions
asthma.
Frontiers in Oncology,
Год журнала:
2025,
Номер
14
Опубликована: Янв. 7, 2025
Cancer's
epigenetic
landscape,
a
labyrinthine
tapestry
of
molecular
modifications,
has
long
captivated
researchers
with
its
profound
influence
on
gene
expression
and
cellular
fate.
This
review
discusses
the
intricate
mechanisms
underlying
cancer
epigenetics,
unraveling
complex
interplay
between
DNA
methylation,
histone
chromatin
remodeling,
non-coding
RNAs.
We
navigate
through
tumultuous
seas
dysregulation,
exploring
how
these
processes
conspire
to
silence
tumor
suppressors
unleash
oncogenic
potential.
The
narrative
pivots
cutting-edge
technologies,
revolutionizing
our
ability
decode
epigenome.
From
granular
insights
single-cell
epigenomics
holistic
view
offered
by
multi-omics
approaches,
we
examine
tools
are
reshaping
understanding
heterogeneity
evolution.
also
highlights
emerging
techniques,
such
as
spatial
long-read
sequencing,
which
promise
unveil
hidden
dimensions
regulation.
Finally,
probed
transformative
potential
CRISPR-based
epigenome
editing
computational
analysis
transmute
raw
data
into
biological
insights.
study
seeks
synthesize
comprehensive
yet
nuanced
contemporary
landscape
future
directions
research.
Aging,
Год журнала:
2024,
Номер
16(22), С. 13452 - 13504
Опубликована: Дек. 29, 2024
The
ability
to
accurately
quantify
biological
age
could
help
monitor
and
control
healthy
aging.
Epigenetic
clocks
have
emerged
as
promising
tools
for
estimating
age,
yet
they
been
developed
from
heterogeneous
bulk
tissues,
are
thus
composites
of
two
aging
processes,
one
reflecting
the
change
cell-type
composition
with
another
individual
cell-types.
There
is
a
need
dissect
these
components
epigenetic
clocks,
develop
that
can
yield
estimates
at
resolution.
Here
we
demonstrate
in
blood
brain,
approximately
39%
12%
an
clock's
accuracy
driven
by
underlying
shifts
lymphocyte
neuronal
subsets,
respectively.
Using
brain
liver
tissue
prototypes,
build
validate
neuron
hepatocyte
specific
DNA
methylation
improved
chronological
corresponding
cell
tissue-types.
We
find
glia
display
acceleration
Alzheimer's
Disease
effect
being
strongest
temporal
lobe.
Moreover,
CpGs
small
but
significant
overlap
causal
DamAge-clock,
mapping
key
genes
implicated
neurodegeneration.
clock
found
accelerated
under
various
pathological
conditions.
In
contrast,
non-cell-type
do
not
age-acceleration,
or
only
so
marginally.
summary,
this
work
highlights
importance
dissecting
quantifying
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 21, 2025
Frontotemporal
Lobar
Degeneration
(FTLD)
represents
a
spectrum
of
clinically,
genetically,
and
pathologically
heterogeneous
neurodegenerative
disorders
characterised
by
progressive
atrophy
the
frontal
temporal
lobes
brain.
The
two
major
FTLD
pathological
subgroups
are
FTLD-TDP
FTLD-tau.
While
majority
cases
sporadic,
heterogeneity
also
exists
within
familial
cases,
typically
involving
mutations
in
MAPT,
GRN
or
C9orf72,
which
is
not
fully
explained
known
genetic
mechanisms.
We
sought
to
address
this
gap
investigating
effect
epigenetic
modifications,
specifically
DNA
methylation
variation,
on
genes
associated
with
risk
different
subtypes.
compiled
list
using
text-mining
databases
literature
searches.
Frontal
cortex
profiles
were
derived
from
three
datasets
containing
FTLD-tau:
FTLD1m
(N
=
23)
type
A
C9orf72
mutation
carriers
TDP
Type
C
sporadic
FTLD2m
48)
FTLD-Tau
MAPT
carriers,
B
FTLD3m
163)
supranuclear
palsy
(PSP)
corresponding
controls.
To
investigate
downstream
effects
further,
we
then
leveraged
transcriptomic
proteomic
for
controls
examine
gene
protein
expression
levels.
Our
analysis
revealed
shared
promoter
region
hypomethylation
STX6
across
FTLD-tau
subtypes,
though
largest
size
was
observed
PSP
compared
(delta-beta
-32%,
adjusted-p
value=0.002).
dysregulation
Additionally,
performed
detailed
examination
subtypes
without
presence
nominally
significant
differentially
methylated
CpGs
variable
positions
genes,
often
unique
patterns
consequences
gene/protein
carriers.
highlight
contribution
at
regions
regulating
previously
FTLD,
including
STX6.
analysed
relationship
mechanism
increase
our
understanding
how
these
mechanisms
interact
FTLD.
Arteriosclerosis Thrombosis and Vascular Biology,
Год журнала:
2025,
Номер
unknown
Опубликована: Апрель 17, 2025
Advances
in
genomic
technologies
have
significantly
enhanced
our
understanding
of
both
monogenic
and
polygenic
etiologies
cardiovascular
disease.
In
this
review,
we
explore
how
the
utilization
information
is
bringing
personalized
medicine
approaches
to
forefront
disease
management.
We
discuss
data
can
resolve
diagnostic
uncertainty,
support
cascade
screening,
inform
treatment
strategies.
The
role
that
genome-wide
association
studies
had
identifying
thousands
risk
variants
for
diseases,
these
insights,
harnessed
through
development
scores,
could
advance
prediction
beyond
traditional
clinical
algorithms.
detail
pharmacogenomics
leverage
genotype
guide
drug
selection
mitigate
adverse
events.
Finally,
present
paradigm-shifting
approach
gene
therapy,
which
holds
promise
being
a
curative
intervention
conditions.
Epigenomics,
Год журнала:
2025,
Номер
unknown, С. 1 - 12
Опубликована: Май 10, 2025
Early
and
accurate
diagnosis
significantly
improves
the
chances
of
disease
survival.
DNA
methylation
(5mC),
major
modification
in
human
genome,
is
now
recognized
as
a
biomarker
immense
clinical
potential.
This
due
to
its
ability
delineate
precisely
cell-type,
quantitate
both
internal
external
exposures,
well
tracking
chronological
biological
components
aging
process.
Here,
we
survey
current
state
predictor
traits
disease.
includes
Epigenome-wide
association
study
(EWAS)
findings
that
inform
Methylation
Risk
Scores
(MRS),
EpiScore
long-term
estimators
plasma
protein
levels,
machine
learning
(ML)
derived
clocks.
These
all
highlight
significant
benefits
accessible
peripheral
blood
surrogate
measure.
However,
detailed
biopsy
analysis
real-time
also
empowering
pathological
diagnosis.
Furthermore,
moving
forward,
this
multi-omic
biobank
scale
era,
novel
insights
will
be
enabled
by
amplified
power
increasing
sample
sizes
data
integration.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 31, 2024
The
ability
to
accurately
quantify
biological
age
could
help
monitor
and
control
healthy
aging.
Epigenetic
clocks
have
emerged
as
promising
tools
for
estimating
age,
yet
they
been
developed
from
heterogeneous
bulk
tissues,
are
thus
composites
of
two
aging
processes,
one
reflecting
the
change
cell-type
composition
with
another
individual
cell-types.
There
is
a
need
dissect
these
components
epigenetic
clocks,
develop
that
can
yield
estimates
at
resolution.
Here
we
demonstrate
in
blood
brain,
approximately
39%
12%
an
accuracy
driven
by
underlying
shifts
lymphocyte
neuronal
subsets,
respectively.
Using
brain
liver
tissue
prototypes,
build
validate
neuron
hepatocyte
specific
DNA
methylation
improved
chronological
corresponding
cell
tissue-types.
We
find
glia
display
acceleration
Alzheimers
Disease
effect
being
strongest
temporal
lobe.
Moreover,
CpGs
small
but
significant
overlap
causal
DamAge-clock,
mapping
key
genes
implicated
neurodegeneration.
clock
found
accelerated
under
various
pathological
conditions.
In
contrast,
non-cell-type
do
not
age-acceleration,
or
only
so
marginally.
summary,
this
work
highlights
importance
dissecting
quantifying
Current Opinion in Pulmonary Medicine,
Год журнала:
2024,
Номер
unknown
Опубликована: Июль 31, 2024
Sleep
disorders
encompass
a
wide
range
of
conditions
with
substantial
individual
variability.
Epigenetics,
the
study
heritable
changes
beyond
DNA
sequence,
offers
promising
avenue
for
personalized
medicine
in
this
field.
Advances in Therapy,
Год журнала:
2024,
Номер
unknown
Опубликована: Ноя. 13, 2024
Childhood
obesity
is
a
significant
global
health
challenge
with
rising
prevalence
over
the
past
50
years,
affecting
both
immediate
and
long-term
outcomes.
The
increase
in
from
0.7%
to
5.6%
girls
0.9%
7.8%
boys
highlights
urgency
of
addressing
this
epidemic.
By
2025,
it
estimated
that
206
million
children
adolescents
aged
5-19
years
will
be
living
obesity.
This
review
explores
complex
interplay
genomics
genetics
pediatric
obesity,
transitioning
monogenic
polygenic
epigenetics,
incorporating
advancements
omics
technologies.
evolutionary
purpose
adiposity,
systemic
evaluation
hyperphagia,
role
various
genetic
factors
are
discussed.
Technological
genotyping
offer
new
insights
interventions.
integration
screening
into
clinical
practice
for
early
identification
personalized
treatment
strategies
emphasized.