Clinical and Translational Medicine,
Год журнала:
2023,
Номер
13(11)
Опубликована: Ноя. 1, 2023
Abstract
Background
Alternative
splicing
(AS)
is
an
omnipresent
regulatory
mechanism
of
gene
expression
that
enables
the
generation
diverse
splice
isoforms
from
a
single
gene.
Recently,
AS
events
have
gained
considerable
momentum
in
pathogenesis
inflammatory
bowel
disease
(IBD).
Methods
Our
review
has
summarized
complex
process
RNA
splicing,
and
firstly
highlighted
potential
involved
molecules
target
aberrant
IBD.
The
quantitative
transcriptome
analyses
such
as
microarrays,
next‐generation
sequencing
(NGS)
for
IBD
been
also
discussed.
Results
Available
evidence
suggests
some
abnormal
RNAs
can
lead
to
multiple
intestinal
disorders
during
onset
well
progression
colitis‐associated
cancer
(CAC),
including
gut
microbiota
perturbations,
barrier
dysfunctions,
innate/adaptive
immune
dysregulations,
pro‐fibrosis
activation
other
risk
factors.
Moreover,
current
data
show
advanced
technologies,
microarrays
NGS,
pioneeringly
employed
screen
candidates
elucidate
mechanisms
Besides,
biotechnological
progresses
applications
third‐generation
(TGS),
single‐cell
(scRNA‐seq)
spatial
transcriptomics
(ST),
will
be
desired
with
great
expectations.
Conclusions
To
our
knowledge,
first
one
evaluate
expanding
list
aberrantly
spliced
genes
along
developed
technologies
provide
us
new
clues
how
develops,
these
important
explored
future
treatment.
Nature,
Год журнала:
2024,
Номер
630(8016), С. 447 - 456
Опубликована: Июнь 5, 2024
Abstract
Increasing
rates
of
autoimmune
and
inflammatory
disease
present
a
burgeoning
threat
to
human
health
1
.
This
is
compounded
by
the
limited
efficacy
available
treatments
high
failure
during
drug
development
2
,
highlighting
an
urgent
need
better
understand
mechanisms.
Here
we
show
how
functional
genomics
could
address
this
challenge.
By
investigating
intergenic
haplotype
on
chr21q22—which
has
been
independently
linked
bowel
disease,
ankylosing
spondylitis,
primary
sclerosing
cholangitis
Takayasu’s
arteritis
3–6
—we
identify
that
causal
gene,
ETS2
central
regulator
macrophages
delineate
shared
mechanism
amplifies
expression.
Genes
regulated
were
prominently
expressed
in
diseased
tissues
more
enriched
for
GWAS
hits
than
most
previously
described
pathways.
Overexpressing
resting
reproduced
state
observed
chr21q22-associated
diseases,
with
upregulation
multiple
targets,
including
TNF
IL-23.
Using
database
cellular
signatures
7
identified
drugs
might
modulate
pathway
validated
potent
anti-inflammatory
activity
one
class
small
molecules
vitro
ex
vivo.
Together,
illustrates
power
genomics,
applied
directly
cells,
immune-mediated
mechanisms
potential
therapeutic
opportunities.
Gut,
Год журнала:
2024,
Номер
73(8), С. 1376 - 1387
Опубликована: Май 22, 2024
Background
Metabolic
disorders
and
inflammatory
bowel
diseases
(IBD)
have
captured
the
globe
during
Westernisation
of
lifestyle
related
dietary
habits
over
last
decades.
Both
disease
entities
are
characterised
by
complex
heterogeneous
clinical
spectra
linked
to
distinct
symptoms
organ
systems
which,
on
a
first
glimpse,
do
not
many
commonalities
in
practice.
However,
experimental
studies
indicate
common
backbone
mechanisms
metabolic
gut
inflammation,
emerging
evidence
suggests
an
intricate
interplay
between
IBD.
Objective
We
depict
parallels
IBD
diseases,
easily
overlooked
routine.
Design
provide
overview
recent
literature
discuss
implications
morbidity
patients
with
for
researchers,
clinicians
healthcare
providers.
Conclusion
The
Western
diet
microbial
perturbation
serve
as
fuel
inflammation
beyond
gut.
syndrome
increasingly
affect
IBD,
expected
negative
impact
both
risk
complications.
This
concept
implies
that
tackling
obesity
pandemic
exerts
beneficial
effects
health.
Nature Methods,
Год журнала:
2024,
Номер
21(8), С. 1546 - 1557
Опубликована: Июль 22, 2024
Understanding
protein
function
and
developing
molecular
therapies
require
deciphering
the
cell
types
in
which
proteins
act
as
well
interactions
between
proteins.
However,
modeling
across
biological
contexts
remains
challenging
for
existing
algorithms.
Here
we
introduce
PINNACLE,
a
geometric
deep
learning
approach
that
generates
context-aware
representations.
Leveraging
multiorgan
single-cell
atlas,
PINNACLE
learns
on
contextualized
interaction
networks
to
produce
394,760
representations
from
156
type
24
tissues.
PINNACLE's
embedding
space
reflects
cellular
tissue
organization,
enabling
zero-shot
retrieval
of
hierarchy.
Pretrained
can
be
adapted
downstream
tasks:
enhancing
3D
structure-based
resolving
immuno-oncological
interactions,
investigating
drugs'
effects
types.
outperforms
state-of-the-art
models
nominating
therapeutic
targets
rheumatoid
arthritis
inflammatory
bowel
diseases
pinpoints
with
higher
predictive
capability
than
context-free
models.
ability
adjust
its
outputs
basis
context
it
operates
paves
way
large-scale
context-specific
predictions
biology.
Nature Genetics,
Год журнала:
2023,
Номер
55(11), С. 1998 - 2008
Опубликована: Окт. 12, 2023
Abstract
Joint
analysis
of
single-cell
genomics
data
from
diseased
tissues
and
a
healthy
reference
can
reveal
altered
cell
states.
We
investigate
whether
integrated
collections
individuals
(cell
atlases)
are
suitable
references
for
disease-state
identification
matched
control
samples
needed
to
minimize
false
discoveries.
demonstrate
that
using
atlas
latent
space
learning
followed
by
differential
against
controls
leads
improved
disease-associated
cells,
especially
with
multiple
perturbed
types.
Additionally,
when
an
is
available,
reducing
sample
numbers
does
not
increase
discovery
rates.
Jointly
analyzing
COVID-19
cohort
blood
atlas,
we
improve
detection
infection-related
states
linked
distinct
clinical
severities.
Similarly,
studied
disease
in
pulmonary
fibrosis
lung
characterizing
two
aberrant
basal
Our
provides
guidelines
designing
studies
optimizing
use.
