bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 3, 2025
Abstract
Single-cell
technologies
enable
high-resolution,
multi-dimensional
analysis
of
molecular
profiles
in
cancer
biology
but
face
challenges
related
to
low
coverage
and
cell
annotation.
The
inherent
hetero-geneity
complexity
brain
tumors
may
hinder
large-scale
single
multi-omic
profiling.
An
efficient
alternative
is
digital
dissociation,
which
involves
quantifying
abundance
purifying
bulk
samples
at
high
resolution.
However,
most
existing
tools
for
resolving
transcriptomes
using
scRNA-seq
as
a
reference
are
not
easily
transferred
other
omics
(e.g.,
chromatin
accessibility,
DNA
methylation,
protein)
due
ambiguous
markers.
Here,
we
introduce
MODE,
novel
multimodal
autoencoder
neural
network
designed
jointly
recover
personalized
estimate
cellular
compositions.
MODE
the
first
algorithm
trained
on
pseudo-bulk
multi-omics
derived
from
an
external
individualized
non-RNA
panel
constructed
target
tumors.
accuracy
was
evaluated
through
extensive
simulation
study,
generated
realistic
data
distinct
tissue
types.
outperformed
deconvolution
pipelines
with
superior
generalizability.
Additionally,
high-resolution
purified
by
showed
strong
fidelity
enhanced
power
detect
differentially
expressed
genes.
We
applied
methylome-transcriptome
two
independent
tumor
cohorts,
revealing
modality-specific
landscapes
pediatric
medul-loblastoma
(MB)
adult
glioblastoma
(GBM).
In
MB
tumors,
accurately
predicted
composition
embryonal
lineage
cells
their
marker
genes
expression.
GBM,
deconvoluted
revealed
increased
myeloid
associated
poorer
event-free
survival.
Overall,
dissociation
unravels
origins,
evolution,
prognosis
offering
powerful
tool
state
resolution
without
sequencing.
pipeline
freely
available
https://github.com/jsuncompubio/MODE
.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2023,
Номер
unknown
Опубликована: Дек. 8, 2023
Emerging
imaging
spatial
transcriptomics
(iST)
platforms
and
coupled
analytical
methods
can
recover
cell-to-cell
interactions,
groups
of
spatially
covarying
genes,
gene
signatures
associated
with
pathological
features,
are
thus
particularly
well-suited
for
applications
in
formalin
fixed
paraffin
embedded
(FFPE)
tissues.
Here,
we
benchmarked
the
performance
three
commercial
iST
on
serial
sections
from
tissue
microarrays
(TMAs)
containing
23
tumor
normal
types
both
relative
technical
biological
performance.
On
matched
found
that
10x
Xenium
shows
higher
transcript
counts
per
without
sacrificing
specificity,
but
all
concord
to
orthogonal
RNA-seq
datasets
perform
resolved
cell
typing,
albeit
different
false
discovery
rates,
segmentation
error
frequencies,
varying
degrees
sub-clustering
downstream
analyses.
Taken
together,
our
analyses
provide
a
comprehensive
benchmark
guide
choice
method
as
researchers
design
studies
precious
samples
this
rapidly
evolving
field.
Nature Genetics,
Год журнала:
2024,
Номер
56(4), С. 652 - 662
Опубликована: Март 28, 2024
Abstract
Here
we
use
single-cell
RNA
sequencing
to
compile
a
human
breast
cell
atlas
assembled
from
55
donors
that
had
undergone
reduction
mammoplasties
or
risk
mastectomies.
From
more
than
800,000
cells
identified
41
subclusters
across
the
epithelial,
immune
and
stromal
compartments.
The
contribution
of
these
different
clusters
varied
according
natural
history
tissue.
Age,
parity
germline
mutations,
known
modulate
developing
cancer,
affected
homeostatic
cellular
state
in
ways.
We
found
BRCA1
BRCA2
carriers
distinct
gene
expression
signature
indicative
potential
exhaustion,
which
was
validated
by
immunohistochemistry.
This
suggests
immune-escape
mechanisms
could
manifest
non-cancerous
tissues
very
early
during
tumor
initiation.
is
rich
resource
can
be
used
inform
novel
approaches
for
detection
prevention
cancer.
Nature Biotechnology,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 4, 2025
Abstract
Tumors
exhibit
an
increased
ability
to
obtain
and
metabolize
nutrients.
Here,
we
implant
engineered
adipocytes
that
outcompete
tumors
for
nutrients
show
they
can
substantially
reduce
cancer
progression,
a
technology
termed
adipose
manipulation
transplantation
(AMT).
Adipocytes
use
amounts
of
glucose
fatty
acids
by
upregulating
UCP1
were
placed
alongside
cells
or
xenografts,
leading
significant
suppression.
Transplanting
modulated
organoids
in
pancreatic
breast
genetic
mouse
models
suppressed
their
growth
decreased
angiogenesis
hypoxia.
Co-culturing
patient-derived
with
tumor
from
dissected
human
cancers
significantly
progression
proliferation.
In
addition,
was
impaired
inducing
using
tetracycline
placing
them
integrated
cell-scaffold
delivery
platform
implanting
next
the
tumor.
Finally,
UPP1
uridine-dependent
ductal
adenocarcinoma
uridine
suppress
its
growth,
demonstrating
potential
customization
AMT.
Nature Communications,
Год журнала:
2025,
Номер
16(1)
Опубликована: Янв. 3, 2025
The
fallopian
tube
undergoes
extensive
molecular
changes
during
the
menstrual
cycle
and
menopause.
We
use
single-cell
RNA
ATAC
sequencing
to
construct
a
comprehensive
cell
atlas
of
healthy
human
tubes
Our
scRNA-seq
comparison
85,107
pre-
46,111
post-menopausal
cells
reveals
substantial
shifts
in
type
frequencies,
gene
expression,
transcription
factor
activity,
cell-to-cell
communications
menopause
cycle.
Menstrual
dependent
hormonal
regulate
distinct
states
secretory
epithelial
cells.
Postmenopausal
show
high
chromatin
accessibility
factors
associated
with
aging
such
as
Jun,
Fos,
BACH1/2,
while
hormone
receptors
were
generally
downregulated,
small
proportion
had
expression
ESR2,
IGF1R,
LEPR.
While
pre-menopausal
cluster
is
enriched
immunoreactive
subtype,
subset
genes
expressed
enrichment
mesenchymal
high-grade
serous
ovarian
cancer.
cellular
aging.
Here,
Weigert
et
al.
present
normal
revealing
transition
throughout
The
ability
to
map
a
proteomic
fingerprint
transcriptomic
data
would
master
the
understanding
of
how
gene
expression
translates
into
actual
phenotype.
In
contrast
nucleic
acid
sequencing,
in
vitro
protein
amplification
is
impossible
and
no
single
cell
workflow
has
been
established
as
gold
standard
yet.
Advances
microfluidic
sample
preparation,
multi-dimensional
separation,
sophisticated
acquisition
strategies,
intelligent
analysis
algorithms
have
resulted
major
improvements
successfully
analyze
such
tiny
amounts
with
steadily
boosted
performance.
However,
among
broad
variation
published
approaches,
it
commonly
accepted
that
highest
possible
sensitivity,
robustness,
throughput
are
still
most
urgent
needs
for
field.
While
many
labs
focused
on
multiplexing
achieve
these
goals,
label-free
SCP
highly
promising
strategy
well
whenever
high
dynamic
range
unbiased
accurate
quantification
needed.
We
here
focus
recent
advances
single-cell
mass
spectrometry
workflows
try
guide
our
readers
choose
best
method
or
combinations
methods
their
specific
applications.
further
highlight
which
techniques
propitious
future
applications
but
also
limitations
we
foresee
