Genome biology,
Journal Year:
2023,
Volume and Issue:
24(1)
Published: Oct. 24, 2023
Single-cell
RNA-sequencing
(scRNA-seq)
measures
gene
expression
in
single
cells,
while
single-nucleus
ATAC-sequencing
(snATAC-seq)
quantifies
chromatin
accessibility
nuclei.
These
two
data
types
provide
complementary
information
for
deciphering
cell
and
states.
However,
when
analyzed
individually,
they
sometimes
produce
conflicting
results
regarding
type/state
assignment.
The
power
is
compromised
since
the
modalities
reflect
same
underlying
biology.
Recently,
it
has
become
possible
to
measure
both
from
nucleus.
Such
paired
enable
direct
modeling
of
relationships
between
modalities.
Given
availability
vast
amount
single-modality
data,
desirable
integrate
unpaired
datasets
gain
a
comprehensive
view
cellular
complexity.
Nature,
Journal Year:
2023,
Volume and Issue:
614(7949), P. 742 - 751
Published: Feb. 8, 2023
Abstract
Cell
identity
is
governed
by
the
complex
regulation
of
gene
expression,
represented
as
gene-regulatory
networks
1
.
Here
we
use
inferred
from
single-cell
multi-omics
data
to
perform
in
silico
transcription
factor
perturbations,
simulating
consequent
changes
cell
using
only
unperturbed
wild-type
data.
We
apply
this
machine-learning-based
approach,
CellOracle,
well-established
paradigms—mouse
and
human
haematopoiesis,
zebrafish
embryogenesis—and
correctly
model
reported
phenotype
that
occur
a
result
perturbation.
Through
systematic
perturbation
developing
zebrafish,
simulate
experimentally
validate
previously
unreported
results
loss
noto
,
an
established
notochord
regulator.
Furthermore,
identify
axial
mesoderm
regulator,
lhx1a
Together,
these
show
CellOracle
can
be
used
analyse
factors,
provide
mechanistic
insights
into
development
differentiation.
Nature Methods,
Journal Year:
2023,
Volume and Issue:
20(9), P. 1355 - 1367
Published: July 13, 2023
Abstract
Joint
profiling
of
chromatin
accessibility
and
gene
expression
in
individual
cells
provides
an
opportunity
to
decipher
enhancer-driven
regulatory
networks
(GRNs).
Here
we
present
a
method
for
the
inference
GRNs,
called
SCENIC+.
SCENIC+
predicts
genomic
enhancers
along
with
candidate
upstream
transcription
factors
(TFs)
links
these
target
genes.
To
improve
both
recall
precision
TF
identification,
curated
clustered
motif
collection
more
than
30,000
motifs.
We
benchmarked
on
diverse
datasets
from
different
species,
including
human
peripheral
blood
mononuclear
cells,
ENCODE
cell
lines,
melanoma
states
Drosophila
retinal
development.
Next,
exploit
predictions
study
conserved
TFs,
GRNs
between
mouse
types
cerebral
cortex.
Finally,
use
dynamics
regulation
differentiation
trajectories
effect
perturbations
state.
is
available
at
scenicplus.readthedocs.io
.
Nature,
Journal Year:
2023,
Volume and Issue:
616(7955), P. 113 - 122
Published: March 15, 2023
Abstract
Emerging
spatial
technologies,
including
transcriptomics
and
epigenomics,
are
becoming
powerful
tools
for
profiling
of
cellular
states
in
the
tissue
context
1–5
.
However,
current
methods
capture
only
one
layer
omics
information
at
a
time,
precluding
possibility
examining
mechanistic
relationship
across
central
dogma
molecular
biology.
Here,
we
present
two
technologies
spatially
resolved,
genome-wide,
joint
epigenome
transcriptome
by
cosequencing
chromatin
accessibility
gene
expression,
or
histone
modifications
(H3K27me3,
H3K27ac
H3K4me3)
expression
on
same
section
near-single-cell
resolution.
These
were
applied
to
embryonic
juvenile
mouse
brain,
as
well
adult
human
map
how
epigenetic
mechanisms
control
transcriptional
phenotype
cell
dynamics
tissue.
Although
highly
concordant
features
identified
either
also
observed
distinct
patterns,
suggesting
their
differential
roles
defining
states.
Linking
pixel
allows
uncovering
new
insights
priming,
differentiation
regulation
within
architecture.
great
interest
life
science
biomedical
research.
Science,
Journal Year:
2022,
Volume and Issue:
377(6606)
Published: Aug. 4, 2022
Drosophila
melanogaster
is
a
powerful,
long-standing
model
for
metazoan
development
and
gene
regulation.
We
profiled
chromatin
accessibility
in
almost
1
million
expression
half
nuclei
from
overlapping
windows
spanning
the
entirety
of
embryogenesis.
Leveraging
developmental
asynchronicity
within
embryo
collections,
we
applied
deep
neural
networks
to
infer
age
each
nucleus,
resulting
continuous,
multimodal
views
molecular
cellular
transitions
absolute
time.
identify
cell
lineages;
their
relationships;
link
dynamic
changes
enhancer
usage,
transcription
factor
(TF)
expression,
TFs’
cognate
motifs.
With
these
data,
dynamics
usage
can
be
explored
across
lineages
at
scale
minutes,
including
precise
like
zygotic
genome
activation.
Science Advances,
Journal Year:
2023,
Volume and Issue:
9(41)
Published: Oct. 12, 2023
The
cellular
complexity
of
the
human
brain
is
established
via
dynamic
changes
in
gene
expression
throughout
development
that
mediated,
part,
by
spatiotemporal
activity
cis-regulatory
elements
(CREs).
We
simultaneously
profiled
and
chromatin
accessibility
45,549
cortical
nuclei
across
six
broad
developmental
time
points
from
fetus
to
adult.
identified
cell
type-specific
domains
which
highly
correlated
with
expression.
Differentiation
pseudotime
trajectory
analysis
indicates
at
CREs
precedes
transcription
structure
play
a
critical
role
neuronal
lineage
commitment.
In
addition,
we
mapped
temporally
specific
genetic
loci
implicated
neuropsychiatric
traits,
including
schizophrenia
bipolar
disorder.
Together,
our
results
describe
complex
regulation
composition
stages
determination
shed
light
on
impact
alterations
disease.
