Briefings in Bioinformatics,
Journal Year:
2025,
Volume and Issue:
26(3)
Published: May 1, 2025
Abstract
Single-cell
sequencing
has
advanced
our
understanding
of
cellular
heterogeneity
and
disease
pathology,
offering
insights
into
behavior
immune
mechanisms.
However,
extracting
meaningful
phenotype-related
features
is
challenging
due
to
noise,
batch
effects,
irrelevant
biological
signals.
To
address
this,
we
introduce
Deep
scSTAR
(DscSTAR),
a
deep
learning-based
tool
designed
enhance
phenotype-associated
features.
DscSTAR
identified
HSP+
FKBP4+
T
cells
in
CD8+
cells,
which
linked
dysfunction
resistance
checkpoint
blockade
non-small
cell
lung
cancer.
It
also
enhanced
spatial
transcriptomics
analysis
renal
carcinoma,
revealing
interactions
between
cancer
tumor-associated
macrophages
that
may
promote
suppression
affect
outcomes.
In
hepatocellular
it
highlighted
the
role
S100A12+
neutrophils
cancer-associated
fibroblasts
forming
tumor
barriers
potentially
contributing
immunotherapy
resistance.
These
findings
demonstrate
DscSTAR’s
capacity
model
extract
phenotype-specific
information,
advancing
mechanisms
therapy
Cardiovascular
diseases
constitute
a
marked
threat
to
global
health,
and
the
emergence
of
spatial
omics
technologies
has
revolutionized
cardiovascular
research.
This
review
explores
application
omics,
including
transcriptomics,
proteomics,
metabolomics,
genomics,
epigenomics,
providing
more
insight
into
molecular
cellular
foundations
disease
highlighting
critical
contributions
science,
discusses
future
prospects,
technological
advancements,
integration
multi-omics,
clinical
applications.
These
developments
should
contribute
understanding
guide
progress
precision
medicine,
targeted
therapies,
personalized
treatments.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: March 1, 2025
Recent
advances
in
spatial
transcriptomics
(ST)
technologies
have
transformed
our
ability
to
profile
gene
expression
while
retaining
the
crucial
context
within
tissues.
However,
existing
ST
platforms
suffer
from
high
costs,
long
turnaround
times,
low
resolution,
limited
coverage,
and
small
tissue
capture
areas,
which
hinder
their
broad
applications.
Here
we
present
iSCALE,
a
method
that
predicts
super-resolution
automatically
annotates
cellular-level
architecture
for
large-sized
tissues
exceed
areas
of
standard
platforms.
The
accuracy
iSCALE
were
validated
by
comprehensive
evaluations,
involving
benchmarking
experiments,
immunohistochemistry
staining,
manual
annotation
pathologists.
When
applied
multiple
sclerosis
human
brain
samples,
uncovered
lesion
associated
cellular
characteristics
undetectable
conventional
experiments.
Our
results
demonstrate
iSCALE's
utility
analyzing
with
automatic
unbiased
annotation,
inferring
cell
type
composition,
pinpointing
regions
interest
features
not
discernible
through
visual
assessment.
Nature Communications,
Journal Year:
2025,
Volume and Issue:
16(1)
Published: March 27, 2025
Spatial
omics
technologies
enable
analysis
of
gene
expression
and
interaction
dynamics
in
relation
to
tissue
structure
function.
However,
existing
computational
methods
may
not
properly
distinguish
cellular
intrinsic
variability
intercellular
interactions,
thus
fail
reliably
capture
spatial
regulations.
Here,
we
present
Interaction
Modeling
using
Variational
Inference
(SIMVI),
an
annotation-free
deep
learning
framework
that
disentangles
cell
spatial-induced
latent
variables
data
with
rigorous
theoretical
support.
By
this
disentanglement,
SIMVI
enables
estimation
effects
at
a
single-cell
resolution,
empowers
various
downstream
analyses.
We
demonstrate
the
superior
performance
across
datasets
from
diverse
platforms
tissues.
illuminates
cyclical
germinal
center
B
cells
human
tonsil.
Applying
multiome
melanoma
reveals
potential
tumor
epigenetic
reprogramming
states.
On
our
newly-collected
cohort-level
CosMx
data,
uncovers
space-and-outcome-dependent
macrophage
states
communication
machinery
microenvironments.
Dissecting
properties
interactions
is
crucial
for
understanding
biological
processes.
authors
develop
theoretically
grounded
SIMVI,
two
factors
data.
medRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2025,
Volume and Issue:
unknown
Published: April 23, 2025
Colorectal
cancer
(CRC)
remains
a
major
health
concern,
with
over
150,000
new
diagnoses
and
more
than
50,000
deaths
annually
in
the
United
States,
underscoring
an
urgent
need
for
improved
screening,
prognostication,
disease
management,
therapeutic
approaches.
The
tumor
microenvironment
(TME)-comprising
cancerous
immune
cells
interacting
within
tumor's
spatial
architecture-plays
critical
role
progression
treatment
outcomes,
reinforcing
its
importance
as
prognostic
marker
metastasis
recurrence
risk.
However,
traditional
methods
TME
characterization,
such
bulk
transcriptomics
multiplex
protein
assays,
lack
sufficient
resolution.
Although
(ST)
allows
high-resolution
mapping
of
whole
transcriptomes
at
near-cellular
resolution,
current
ST
technologies
(e.g.,
Visium,
Xenium)
are
limited
by
high
costs,
low
throughput,
issues
reproducibility,
preventing
their
widespread
application
large-scale
molecular
epidemiology
studies.
In
this
study,
we
refined
implemented
Virtual
RNA
Inference
(VRI)
to
derive
ST-level
information
directly
from
hematoxylin
eosin
(H&E)-stained
tissue
images.
Our
VRI
models
were
trained
on
largest
matched
CRC
dataset
date,
comprising
45
patients
300,000
Visium
spots
primary
tumors.
Using
state-of-the-art
architectures
(UNI,
ResNet-50,
ViT,
VMamba),
achieved
median
Spearman's
correlation
coefficient
0.546
between
predicted
measured
spot-level
expression.
As
validation,
VRI-derived
gene
signatures
linked
specific
regions
(tumor,
interface,
submucosa,
stroma,
serosa,
muscularis,
inflammation)
showed
strong
concordance
generated
via
direct
ST,
performed
accurately
estimating
cell-type
proportions
spatially
H&E
slides.
expanded
cohort
controlling
invasiveness
clinical
factors,
further
identified
significantly
associated
key
including
status.
certain
tumor-related
pathways
not
fully
captured
histology
alone,
our
findings
highlight
ability
infer
wide
range
"histology-associated"
biological
resolution
without
requiring
profiling.
Future
efforts
will
extend
framework
expand
phenotyping
standard
images,
potential
accelerate
translational
research
scale.
Briefings in Bioinformatics,
Journal Year:
2025,
Volume and Issue:
26(3)
Published: May 1, 2025
Abstract
Single-cell
sequencing
has
advanced
our
understanding
of
cellular
heterogeneity
and
disease
pathology,
offering
insights
into
behavior
immune
mechanisms.
However,
extracting
meaningful
phenotype-related
features
is
challenging
due
to
noise,
batch
effects,
irrelevant
biological
signals.
To
address
this,
we
introduce
Deep
scSTAR
(DscSTAR),
a
deep
learning-based
tool
designed
enhance
phenotype-associated
features.
DscSTAR
identified
HSP+
FKBP4+
T
cells
in
CD8+
cells,
which
linked
dysfunction
resistance
checkpoint
blockade
non-small
cell
lung
cancer.
It
also
enhanced
spatial
transcriptomics
analysis
renal
carcinoma,
revealing
interactions
between
cancer
tumor-associated
macrophages
that
may
promote
suppression
affect
outcomes.
In
hepatocellular
it
highlighted
the
role
S100A12+
neutrophils
cancer-associated
fibroblasts
forming
tumor
barriers
potentially
contributing
immunotherapy
resistance.
These
findings
demonstrate
DscSTAR’s
capacity
model
extract
phenotype-specific
information,
advancing
mechanisms
therapy