Neural Network-Assisted Humanization of COVID-19 Hamster scRNAseq Data Reveals Matching Severity States in Human Disease
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 12, 2024
Translating
findings
from
animal
models
to
human
disease
is
essential
for
dissecting
mechanisms,
developing
and
testing
precise
therapeutic
strategies.
The
coronavirus
2019
(COVID-19)
pandemic
has
highlighted
this
need,
particularly
showing
severity-dependent
immune
responses.
Single-cell
transcriptomics
(scRNAseq)
well
poised
reveal
similarities
differences
between
species
at
the
molecular
cellular
level
with
unprecedented
resolution.
However,
computational
methods
enabling
detailed
matching
are
still
scarce.
Here,
we
provide
a
structured
scRNAseq-based
approach
that
applied
scRNAseq
blood
leukocytes
originating
humans
hamsters
affected
moderate
or
severe
COVID-19.
Integration
of
COVID-19
patient
data
two
hamster
develop
(Syrian
hamster,
Mesocricetus
auratus)
(Roborovski
Phodopus
roborovskii)
revealed
most
states
shared
across
species.
A
neural
network-based
analysis
using
variational
autoencoders
quantified
overall
transcriptomic
similarity
severity
levels,
highest
neutrophils
Roborovski
patients,
while
Syrian
better
matched
patients
disease,
in
classical
monocytes.
We
further
used
transcriptome-wide
differential
expression
identify
which
stages
cell
types
display
strongest
transcriptional
changes.
Consistently,
hamster's
response
was
similar
monocytes
neutrophils.
Disease-linked
pathways
found
all
specifically
related
interferon
inhibition
viral
replication.
Analysis
candidate
genes
signatures
supported
results.
Our
network-supported
workflow
could
be
other
diseases,
allowing
identification
suitable
pathomechanisms
Язык: Английский
A single-dose MCMV-based vaccine elicits long-lasting immune protection in mice against distinct SARS-CoV-2 variants
Frontiers in Immunology,
Год журнала:
2024,
Номер
15
Опубликована: Июль 25, 2024
Current
vaccines
against
COVID-19
elicit
immune
responses
that
are
overall
strong
but
wane
rapidly.
As
a
consequence,
the
necessary
booster
shots
have
contributed
to
vaccine
fatigue.
Hence,
would
provide
lasting
protection
needed,
still
unavailable.
Cytomegaloviruses
(CMVs)
and
uniquely
responses.
Used
as
vectors,
they
may
be
attractive
tools
obviate
need
for
boosters.
Therefore,
we
tested
murine
CMV
(MCMV)
vector
in
relevant
preclinical
models
of
immunization
challenge.
We
previously
developed
recombinant
MCMV
expressing
spike
protein
ancestral
SARS-CoV-2
(MCMV
Язык: Английский