PLoS Genetics,
Год журнала:
2024,
Номер
20(8), С. e1011356 - e1011356
Опубликована: Авг. 7, 2024
Portability
of
trans-ancestral
polygenic
risk
scores
is
often
confounded
by
differences
in
linkage
disequilibrium
and
genetic
architecture
between
ancestries.
Recent
literature
has
shown
that
prioritizing
GWAS
SNPs
with
functional
genomic
evidence
over
strong
association
signals
can
improve
model
portability.
We
leveraged
three
RegulomeDB-derived
regulatory
annotations—SURF,
TURF,
TLand—to
construct
models
across
a
set
quantitative
binary
traits
highlighting
mutations
tagged
trait-associated
tissue
annotations.
Tissue-specific
prioritization
TURF
TLand
provide
significant
improvement
accuracy
standard
score
(PRS)
all
traits.
developed
the
Trans-ancestral
Iterative
Tissue
Refinement
(TITR)
algorithm
to
PRS
prioritize
multiple
trait-implicated
tissues.
TITR-constructed
show
increased
predictive
single
prioritization.
This
indicates
our
TITR
approach
captures
more
comprehensive
view
systems
implicated
tissues
contribute
variance
trait
expression.
Biochemistry and Biophysics Reports,
Год журнала:
2023,
Номер
37, С. 101589 - 101589
Опубликована: Ноя. 29, 2023
Single-cell
multi-omics
technologies
have
revolutionized
cancer
research
by
allowing
us
to
examine
individual
cells
at
a
molecular
level.
Unlike
traditional
bulk
omics
approaches,
which
analyze
populations
of
together,
single-cell
enables
uncover
the
heterogeneity
within
tumors
and
understand
unique
characteristics
different
cell
populations.
By
doing
so,
we
can
identify
rare
subpopulations
that
are
influential
in
tumor
growth,
metastasis,
resistance
therapy.
Moreover,
analysis
provides
valuable
insights
into
immune
response
triggered
various
therapeutic
interventions,
such
as
checkpoint
blockade,
chemotherapy,
It
also
helps
better
intricate
microenvironment
its
impact
on
patient
prognosis
treatment.
This
comprehensive
review
focuses
recent
advancements
methodologies,
with
an
emphasis
technologies.
highlights
important
role
these
techniques
uncovering
complexity
tumorigenesis
multiple
applications
research,
well
their
equally
great
contributions
other
areas
immunology.
Through
multi-omics,
gain
deeper
understanding
biology
pave
way
for
more
precise
effective
strategies.
Apart
from
those
above,
this
paper
aims
introduce
live
imaging
technology,
latest
developments
protein
detection
techniques,
explore
seamless
integration
technology.
Clinical Oral Investigations,
Год журнала:
2023,
Номер
27(6), С. 2843 - 2849
Опубликована: Фев. 7, 2023
The
purpose
of
this
study
was
to
investigate
whether
there
is
a
causal
relationship
between
periodontitis
and
breast
cancer
by
Mendelian
randomization
analysis.
Abstract
Background
The
vast
majority
of
findings
from
human
genome-wide
association
studies
(GWAS)
map
to
non-coding
sequences,
complicating
their
mechanistic
interpretations
and
clinical
translations.
Non-coding
sequences
that
are
evolutionarily
conserved
biochemically
active
could
offer
clues
the
mechanisms
underpinning
GWAS
discoveries.
However,
genetic
effects
such
have
not
been
systematically
examined
across
a
wide
range
tissues
traits,
hampering
progress
fully
understand
regulatory
causes
complex
traits.
Results
Here
we
develop
simple
yet
effective
strategy
identify
functional
elements
exhibiting
high
levels
human-mouse
sequence
conservation
enhancer-like
biochemical
activity,
which
scales
well
313
epigenomic
datasets
106
cell
types.
Combined
with
468
European
(EUR)
East
Asian
(EAS)
ancestries,
these
show
tissue-specific
enrichments
heritability
causal
variants
for
many
significantly
stronger
than
based
on
enhancers
without
conservation.
These
also
help
prioritize
candidate
genes
functionally
relevant
body
mass
index
(BMI)
schizophrenia
but
were
reported
in
previous
large
sample
sizes.
Conclusions
Our
provide
comprehensive
assessment
how
sequence-conserved
affect
traits
diverse
demonstrate
generalizable
integrating
evolutionary
data
elucidate
disease
genetics.
Journal of the American Heart Association,
Год журнала:
2023,
Номер
12(20)
Опубликована: Окт. 7, 2023
Background
The
relationship
between
mitochondrial
DNA
copy
number
(mtDNA
CN)
and
cardiovascular
disease
remains
elusive.
Methods
Results
We
performed
cross-sectional
prospective
association
analyses
of
blood-derived
mtDNA
CN
outcomes
in
27
316
participants
8
cohorts
multiple
racial
ethnic
groups
with
whole-genome
sequencing.
also
Mendelian
randomization
to
explore
causal
relationships
coronary
heart
(CHD)
cardiometabolic
risk
factors
(obesity,
diabetes,
hypertension,
hyperlipidemia).
Cell Genomics,
Год журнала:
2023,
Номер
3(5), С. 100304 - 100304
Опубликована: Апрель 21, 2023
Genetic
variation
contributes
greatly
to
LDL
cholesterol
(LDL-C)
levels
and
coronary
artery
disease
risk.
By
combining
analysis
of
rare
coding
variants
from
the
UK
Biobank
genome-scale
CRISPR-Cas9
knockout
activation
screening,
we
substantially
improve
identification
genes
whose
disruption
alters
serum
LDL-C
levels.
We
identify
21
in
which
significantly
alter
at
least
partially
through
altered
uptake.
use
co-essentiality-based
gene
module
show
that
dysfunction
RAB10
vesicle
transport
pathway
leads
hypercholesterolemia
humans
mice
by
impairing
surface
receptor
Further,
demonstrate
loss
function
Background:
The
association
between
smoking
dependence
and
the
risk
of
developing
Barrett’s
esophagus
remains
unclear.
This
study
aimed
to
investigate
whether
a
causal
relationship
exists
esophagus,
using
Mendelian
randomization
analysis.
Methods:
Two-sample
analysis
was
conducted
evaluate
impact
esophagus.
Additionally,
we
applied
summary
data-based
techniques
combine
information
from
genome-wide
studies
(GWAS)
with
expression
quantitative
trait
locus
methylation
locus.
Results:
Multivariable
showed
an
per
day
(odds
ratio
=
1.2,
95%
confidence
interval:
1.038–1.38,
p
0.014)
or
current
2.41,
1.06–5.5,
0.037)
Inverse
variance-weighted
methods
bidirectional
also
revealed
that
significantly
associated
elevated
risks
1.34,
1.092–1.649,
0.005),
while
susceptibility
factor
for
1.05,
1.017–1.087,
0.003).
By
incorporating
consistent
associations
DNA
smoke/Barrett’s
gene
expression,
identified
genetic
variant-cg00935895-RBM43
(ENSG00000184898)-smoke/Barrett’s
axis
exerted
effect
on
by
altering
level,
which
regulated
level
RBM43.
Conclusions:
Our
provides
evidence
perspective,
sheds
new
light
potential
role
RBM43
as
mediator
in
facilitating
