bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2022,
Номер
unknown
Опубликована: Июль 7, 2022
Abstract
Protein
networks
are
commonly
used
for
understanding
how
proteins
interact.
However,
they
typically
biased
by
data
availability,
favoring
well-studied
with
more
interactions.
To
uncover
functions
of
understudied
proteins,
we
must
use
that
not
affected
this
literature
bias,
such
as
single-cell
RNA-seq
and
proteomics.
Due
to
sparseness
redundancy,
co-expression
analysis
becomes
complex.
address
this,
have
developed
FAVA
(Functional
Associations
using
Variational
Autoencoders),
which
compresses
high-dimensional
into
a
low-dimensional
space.
infers
from
omics
much
higher
accuracy
than
existing
methods,
across
diverse
collection
real
well
simulated
datasets.
can
process
large
datasets
over
0.5
million
conditions
has
predicted
4,210
interactions
between
1,039
proteins.
Our
findings
showcase
FAVA’s
capability
offer
novel
perspectives
on
protein
within
the
scverse
ecosystem,
employing
AnnData
its
input
source.
European journal of medical research,
Год журнала:
2023,
Номер
28(1)
Опубликована: Дек. 15, 2023
Although
great
progress
has
been
made
in
anti-cancer
therapy,
the
prognosis
of
laryngeal
squamous
cell
carcinoma
(LSCC)
patients
remains
unsatisfied.
Quantities
studies
demonstrate
that
glycolytic
reprograming
is
essential
for
progression
cancers,
where
triosephosphate
isomerase
1
(TPI1)
serves
as
a
catalytic
enzyme.
However,
clinicopathological
significance
and
potential
biological
functions
TPI1
underlying
LSCC
obscure.We
collected
in-house
82
tissue
specimens
56
non-tumor
specimens.
Tissue
microarrays
(TMA)
immunohistochemical
(IHC)
experiments
were
performed.
External
bulk
RNA
sequencing
data
integrated
to
evaluate
expression
TPI1.
We
used
log-rank
test
CIBERSORT
algorithm
assess
prognostic
value
its
association
with
microenvironment.
Malignant
epithelial
cells
immune-stromal
identified
using
inferCNV
CellTypist.
conducted
comprehensive
analysis
elucidate
molecular
single
Pearson
correlation
analysis,
high
dimensional
weighted
gene
co-expression
set
enrichment
clustered
regularly
interspaced
short
palindromic
repeats
(CRISPR)
screen.
explored
intercellular
communication
patterns
between
predicted
several
therapeutic
agents
targeting
TPI1.Based
on
TMA
IHC
protein
was
found
have
strong
positive
nucleus
but
only
weakly
activity
cytoplasm
normal
(p
<
0.0001).
Further
confirmation
elevated
mRNA
obtained
from
external
datasets,
comparing
251
samples
136
non-LSCC
(standardized
mean
difference
=
1.06).
The
upregulated
demonstrated
discriminative
ability
(area
under
curve
0.91;
sensitivity
0.87;
specificity
0.79),
suggesting
predictive
marker
poor
0.037).
Lower
infiltration
abundance
plasma
cells,
naïve
B
monocytes,
neutrophils
TPI-high
tissue.
Glycolysis
cycle
significantly
enriched
pathways
both
heat
shock
family
member
1,
TPI1,
enolase
occupied
central
position.
Four
outgoing
two
incoming
networks.
an
oncogene
LSCC,
CRISPR
scores
less
than
-1
across
71.43%
lines.
positively
correlated
half
maximal
inhibitory
concentration
gemcitabine
cladribine.TPI1
dramatically
overexpressed
tissue,
may
promote
deterioration
through
metabolic
non-metabolic
functions.
This
study
contributes
advancing
our
knowledge
pathogenesis
implications
development
targeted
therapies
future.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Май 31, 2024
The
globus
pallidus
externus
(GPe)
is
a
central
component
of
the
basal
ganglia
circuit,
receiving
strong
input
from
indirect
pathway
and
regulating
variety
functions,
including
locomotor
output
habit
formation.
We
recently
showed
that
it
also
acts
as
gatekeeper
cocaine-induced
behavioral
plasticity,
inhibition
parvalbumin-positive
cells
in
GPe
(GPe
iScience,
Год журнала:
2024,
Номер
27(9), С. 110660 - 110660
Опубликована: Авг. 5, 2024
Highlights•Bulk
and
single-nucleus
RNA-seq
data
from
human
atria
help
interpret
AF
GWAS
results•Co-localization
fine-mapping
implicate
14
genes
at
9
loci•LINC01629
is
involved
in
the
development
of
atrial
tissue
conduction
systemSummaryAtrial
fibrillation
(AF)
most
common
arrhythmia
world.
Human
genetics
can
provide
strong
therapeutic
candidates,
but
identification
causal
their
functions
remains
challenging.
Here,
we
applied
an
strategy
that
leverages
results
a
previously
published
cross-ancestry
genome-wide
association
study
(GWAS),
expression
quantitative
trait
loci
(eQTLs)
left
appendages
(LAAs)
obtained
two
cohorts
with
distinct
ancestry,
paired
RNA
sequencing
(RNA-seq)
ATAC
(ATAC-seq)
LAA
assay
(sn-multiome).
At
nine
loci,
our
co-localization
analyses
implicated
genes.
Data
integration
identified
several
candidate
variants,
including
rs7612445
GNB4
rs242557
MAPT.
Finally,
showed
repression
strongest
AF-associated
eQTL
gene,
LINC01629,
embryonic
stem
cell-derived
cardiomyocytes
using
CRISPR
inhibition
dysregulation
pathways
linked
to
cardiac
system.Graphical
abstract
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2022,
Номер
unknown
Опубликована: Июль 7, 2022
Abstract
Protein
networks
are
commonly
used
for
understanding
how
proteins
interact.
However,
they
typically
biased
by
data
availability,
favoring
well-studied
with
more
interactions.
To
uncover
functions
of
understudied
proteins,
we
must
use
that
not
affected
this
literature
bias,
such
as
single-cell
RNA-seq
and
proteomics.
Due
to
sparseness
redundancy,
co-expression
analysis
becomes
complex.
address
this,
have
developed
FAVA
(Functional
Associations
using
Variational
Autoencoders),
which
compresses
high-dimensional
into
a
low-dimensional
space.
infers
from
omics
much
higher
accuracy
than
existing
methods,
across
diverse
collection
real
well
simulated
datasets.
can
process
large
datasets
over
0.5
million
conditions
has
predicted
4,210
interactions
between
1,039
proteins.
Our
findings
showcase
FAVA’s
capability
offer
novel
perspectives
on
protein
within
the
scverse
ecosystem,
employing
AnnData
its
input
source.