Journal of Proteome Research,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 31, 2024
Recent
improvements
in
proteomics
technologies
have
fundamentally
altered
our
capacities
to
characterize
human
biology.
There
is
an
ever-growing
interest
using
these
novel
methods
for
studying
the
circulating
proteome,
as
blood
offers
accessible
window
into
health.
However,
every
methodological
innovation
and
analytical
progress
calls
reassessing
existing
approaches
routines
ensure
that
new
data
will
add
value
greater
biomedical
research
community
avoid
previous
errors.
As
representatives
of
HUPO's
Human
Plasma
Proteome
Project
(HPPP),
we
present
2024
survey
current
community,
including
latest
build
PeptideAtlas
now
comprises
4608
proteins
detected
113
sets.
We
then
discuss
updates
established
methods,
emerging
technologies,
investigations
proteoforms,
protein
networks,
extracellualr
vesicles,
antibodies
microsamples.
Finally,
provide
a
prospective
view
tools
studies
proteins.
Frontiers in Immunology,
Год журнала:
2022,
Номер
13
Опубликована: Дек. 14, 2022
Background
Previous
studies
have
revealed
the
role
of
dysregulated
urokinase
plasminogen
activator
(encoded
by
PLAU
)
expression
and
activity
in
several
pathways
associated
with
cancer
progression.
However,
systematic
investigation
into
association
factors
that
modulate
PDAC
(pancreatic
ductal
adenocarcinoma)
progression
is
lacking,
such
as
those
affecting
stromal
stellate
cell,
PSC)-cancer
cell
interactions,
tumour
immunity,
subtypes
clinical
outcomes
from
potential
inhibition.
Methods
This
study
used
an
integrated
bioinformatics
approach
to
identify
prognostic
markers
correlated
using
different
transcriptomics,
proteomics,
data
sets.
We
then
determined
signatures
oncogenic
pathways,
metastatic
phenotypes,
stroma,
immunosuppressive
microenvironment
(TME)
outcome.
Finally,
vivo
orthotopic
model
pancreatic
cancer,
we
confirmed
predicted
effect
inhibiting
on
growth
metastasis.
Results
Our
analyses
upregulation
not
only
numerous
other
but
also
activation
various
signalling
aggressive
phenotypes
relevant
metastasis,
proliferation,
epithelial-mesenchymal
transition
(EMT),
stemness,
hypoxia,
extracellular
matrix
(ECM)
degradation,
signatures,
immune
suppression
(TME).
Moreover,
was
directly
connected
known
mediate
PSC-cancer
interactions.
Furthermore,
basal/squamous
phenotype
significantly
reduced
overall
survival,
indicating
this
subset
patients
may
benefit
therapeutic
interventions
inhibit
activity.
a
clinically
showed
even
short-term
inhibition
sufficient
halt
and,
importantly,
eliminate
visible
Conclusion
Elevated
correlates
increased
score,
PDAC.
closely
basal
subtype
type
PDAC;
are
at
high
risk
mortality
disease
targeting
.
Abstract
Increased
throughput
in
proteomic
experiments
can
improve
accessibility
of
platforms,
reduce
costs,
and
facilitate
new
approaches
systems
biology
biomedical
research.
Here
we
propose
combination
analytical
flow
rate
chromatography
with
ion
mobility
separation
peptide
ions,
data‐independent
acquisition,
data
analysis
the
DIA‐NN
software
suite,
to
achieve
high‐quality
from
limited
sample
amounts,
at
a
up
400
samples
per
day.
For
instance,
when
benchmarking
our
workflow
using
500‐μL/min
3‐min
chromatographic
gradients,
report
quantification
5211
proteins
2
μg
mammalian
cell‐line
standard
high
quantitative
accuracy
precision.
We
further
used
this
platform
analyze
blood
plasma
cohort
COVID‐19
inpatients,
gradient
alternating
column
regeneration
on
dual
pump
system.
The
method
delivered
comprehensive
view
proteome,
allowing
classification
patients
according
disease
severity
revealing
biomarker
candidates.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Сен. 22, 2023
Abstract
COVID-19
is
characterised
by
systemic
immunological
perturbations
in
the
human
body,
which
can
lead
to
multi-organ
damage.
Many
of
these
processes
are
considered
be
mediated
blood.
Therefore,
better
understand
host
response
SARS-CoV-2
infection,
we
performed
systematic
analyses
circulating,
soluble
proteins
blood
through
global
proteomics
mass-spectrometry
(MS)
proteomics.
Here,
show
that
a
large
part
proteome
altered
COVID-19,
among
them
elevated
levels
interferon-induced
and
proteasomal
proteins.
Some
have
alternating
cells
after
infection
vitro
different
organs
patients
deregulated
blood,
suggesting
shared
infection-related
changes.The
availability
public
proteomic
resources
on
alterations
leaves
uncertainty
about
change
given
protein
during
COVID-19.
Hence,
review
meta-analysis
MS
studies
proteomes,
including
up
1706
individuals
(1039
patients),
provide
concluding
estimates
for
alteration
1517
Finally,
based
developed
CoViMAPP,
an
open-access
resource
effect
sizes
diagnostic
potential
publicly
available
research,
clinical,
academic
community.
Nature Communications,
Год журнала:
2023,
Номер
14(1)
Опубликована: Ноя. 24, 2023
Abstract
Biomarkers
for
early
detection
of
breast
cancer
may
complement
population
screening
approaches
to
enable
earlier
and
more
precise
treatment.
The
blood
proteome
is
an
important
source
biomarker
discovery
but
so
far,
few
proteins
have
been
identified
with
risk.
Here,
we
measure
2929
unique
in
plasma
from
598
women
selected
the
Karolinska
Mammography
Project
explore
association
between
protein
levels,
clinical
characteristics,
gene
variants,
identify
a
causal
role
cancer.
We
present
812
cis-acting
quantitative
trait
loci
737
which
are
used
as
instruments
Mendelian
randomisation
analyses
Of
those,
five
(CD160,
DNPH1,
LAYN,
LRRC37A2
TLR1)
that
show
potential
risk
confirmatory
results
independent
cohorts.
Our
study
suggests
these
should
be
further
explored
biomarkers
drug
targets
Journal of Proteome Research,
Год журнала:
2024,
Номер
23(6), С. 2124 - 2136
Опубликована: Май 3, 2024
Using
proteomics
and
complexome
profiling,
we
evaluated
in
a
year-long
study
longitudinal
variations
the
plasma
proteome
of
kidney
failure
patients,
prior
to
after
transplantation.
The
post-transplant
period
was
complicated
by
bacterial
infections,
resulting
dramatic
changes
proteome,
attributed
an
acute
phase
response
(APR).
As
positive
proteins
(APPs),
being
elevated
upon
inflammation,
observed
well-described
C-reactive
protein
Serum
Amyloid
A
(SAA),
but
also
Fibrinogen,
Haptoglobin,
Leucine-rich
alpha-2-glycoprotein,
Lipopolysaccharide-binding
protein,
Alpha-1-antitrypsin,
Alpha-1-antichymotrypsin,
S100,
CD14.
negative
APPs,
downregulated
identified
well-documented
Serotransferrin
Transthyretin,
added
Kallistatin,
Heparin
cofactor
2,
interalpha-trypsin
inhibitor
heavy
chain
H1
H2
(ITIH1,
ITIH2).
For
patient
with
most
severe
APR,
performed
profiling
SEC-LC-MS
on
all
samples.
We
that
several
displaying
alike
concentration
patterns
coelute
form
macromolecular
complexes.
By
expose
how
SAA1
SAA2
become
incorporated
into
high-density
lipid
particles,
replacing
largely
Apolipoprotein
(APO)A1
APOA4.
Overall,
our
data
highlight
combination
in-depth
can
shed
further
light
correlated
abundance
inflammatory
events.
Journal of Proteome Research,
Год журнала:
2021,
Номер
20(12), С. 5227 - 5240
Опубликована: Окт. 20, 2021
The
2021
Metrics
of
the
HUPO
Human
Proteome
Project
(HPP)
show
that
protein
expression
has
now
been
credibly
detected
(neXtProt
PE1
level)
for
18
357
(92.8%)
19
778
predicted
proteins
coded
in
human
genome,
a
gain
483
since
2020
from
reports
throughout
world
reanalyzed
by
HPP.
Conversely,
number
neXtProt
PE2,
PE3,
and
PE4
missing
reduced
478
to
1421.
This
represents
remarkable
progress
on
proteome
parts
list.
utilization
proteomics
broad
array
biological
clinical
studies
likewise
continues
expand
with
many
important
findings
effective
integration
other
omics
platforms.
We
present
highlights
Immunopeptidomics,
Glycoproteomics,
Infectious
Disease,
Cardiovascular,
Musculo-Skeletal,
Liver,
Cancers
B/D-HPP
teams
Knowledgebase,
Mass
Spectrometry,
Antibody
Profiling,
Pathology
resource
pillars,
as
well
ethical
considerations
biomarkers.
Abstract
Extracellular
vesicles
play
major
roles
in
cell-to-cell
communication
and
are
excellent
biomarker
candidates.
However,
studying
plasma
extracellular
is
challenging
due
to
contaminants.
Here,
we
performed
a
proteomics
meta-analysis
of
public
data
refine
the
EV
composition
by
separating
proteins
contaminants
into
different
clusters.
We
obtained
two
clusters
with
total
1717
that
were
depleted
known
enriched
markers
independently
validated
71%
true-positive.
These
had
133
differentiation
(CD)
antigens
from
signaling.
compared
our
deposited
PeptideAtlas,
making
refined
protein
list
resource
for
mechanistic
studies.
As
use
case
example
this
resource,
type
1
diabetes
proplatelet
basic
EVs
showed
it
regulates
apoptosis
β
cells
macrophages,
key
players
disease
development.
Our
approach
provides
refinement
scientific
community.
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2024,
Номер
unknown
Опубликована: Янв. 8, 2024
Abstract
Alzheimer’s
disease
(AD)
and
related
dementias
(ADRD)
is
a
complex
with
multiple
pathophysiological
drivers
that
determine
clinical
symptomology
progression.
These
diseases
develop
insidiously
over
time,
through
many
pathways
mechanisms
continue
to
have
huge
societal
impact
for
affected
individuals
their
families.
While
emerging
blood-based
biomarkers,
such
as
plasma
p-tau181
p-tau217,
accurately
detect
Alzheimer
neuropthology
are
associated
faster
cognitive
decline,
the
full
extension
of
proteomic
changes
in
ADRD
remains
unknown.
Earlier
detection
better
classification
different
subtypes
may
provide
opportunities
earlier,
more
targeted
interventions,
perhaps
higher
likelihood
successful
therapeutic
development.
In
this
study,
we
aim
leverage
unbiased
mass
spectrometry
proteomics
identify
novel,
biomarkers
decline.
1,786
samples
from
1,005
patients
were
collected
12
years
partcipants
Massachusetts
Disease
Research
Center
Longitudinal
Cohort
Study.
Patient
metadata
includes
demographics,
final
diagnoses,
dementia
rating
(CDR)
scores
taken
concurrently.
The
Proteograph
TM
Product
Suite
(Seer,
Inc.)
liquid-chromatography
mass-spectrometry
(LC-MS)
analysis
used
process
cohort
generate
data.
Data-independent
acquisition
(DIA)
results
yielded
36,259
peptides
4,007
protein
groups.
Linear
mixed
effects
models
revealed
138
differentially
abundant
proteins
between
AD
healthy
controls.
Machine
learning
diagnosis
identified
potential
candidate
including
MBP,
BGLAP,
APoD.
Cox
regression
created
association
progression
suggest
CLNS1A,
CRISPLD2,
GOLPH3
targets
further
investigation
biomarkers.
workflow
provided
deep,
coverage
proteome
at
speed
enabled
study
almost
1,800
samples,
which
largest,
conducted
date.
Clinical Proteomics,
Год журнала:
2024,
Номер
21(1)
Опубликована: Март 12, 2024
Abstract
Despite
progress,
MS-based
proteomics
in
biofluids,
especially
blood,
faces
challenges
such
as
dynamic
range
and
throughput
limitations
biomarker
disease
studies.
In
this
work,
we
used
cutting-edge
technologies
to
construct
label-based
label-free
workflows,
capable
of
quantifying
approximately
2,000
proteins
biofluids.
With
70µL
blood
a
single
depletion
strategy,
conducted
an
analysis
homogenous
cohort
(
n
=
32),
comparing
medium-grade
prostate
cancer
patients
(Gleason
score:
7(3
+
4);
TNM
stage:
T2cN0M0,
stage
IIB)
healthy
donors.
The
results
revealed
dozens
differentially
expressed
both
plasma
serum.
We
identified
the
upregulation
Prostate
Specific
Antigen
(PSA),
well-known
for
cancer,
serum
cohort.
Further
bioinformatics
highlighted
noteworthy
which
appear
be
secreted
into
bloodstream,
making
them
good
candidates
further
exploration.
Molecular & Cellular Proteomics,
Год журнала:
2024,
Номер
23(9), С. 100830 - 100830
Опубликована: Авг. 14, 2024
The
study
of
the
cellular
secretome
using
proteomic
techniques
continues
to
capture
attention
research
community
across
a
broad
range
topics
in
biomedical
research.
Due
their
untargeted
nature,
independence
from
model
system
used,
historically
superior
depth
analysis,
as
well
comparative
affordability,
mass
spectrometry-based
approaches
traditionally
dominate
such
analyses.
More
recently,
however,
affinity-based
assays
have
massively
gained
analytical
depth,
which
together
with
high
sensitivity,
dynamic
coverage
throughput
capabilities
render
them
exquisitely
suited
analysis.
In
this
review,
we
revisit
challenges
implied
by
secretomics
and
provide
an
overview
platforms
currently
available
for
analyses,
tumor
example
basic
translational