Ultradeep N-glycoproteome Atlas of Mouse Reveals Spatiotemporal Signatures of Brain Aging and Neurodegenerative Diseases
bioRxiv (Cold Spring Harbor Laboratory),
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 19, 2025
Abstract
The
current
depth
of
site-specific
N-glycoproteomics
is
insufficient
to
fully
characterize
glycosylation
events
in
biological
samples.
Herein,
we
achieved
an
ultradeep
and
precision
analysis
the
N-glycoproteome
mouse
tissues
by
integrating
multiple
workflows.
largest
N-glycoproteomic
dataset
date
was
established
on
mice,
which
contained
91,972
precursor
glycopeptides,
62,216
glycoforms,
8,939
glycosites
4,563
glycoproteins.
database
consisted
6.8
million
glyco-spectra
(containing
oxonium
ions),
among
160,928
were
high-quality
spectra
with
confident
N-glycopeptide
identifications.
large-scale
enhanced
performance
artificial
intelligence
models
for
glycopeptide
tandem
spectrum
prediction.
Using
this
dataset,
observed
tissue
specific
microheterogeneity
functional
implications
protein
mice.
Furthermore,
region-resolved
brain
N-glycoproteomes
Alzheimer’s
Diseases,
Parkinson
Disease
aging
mice
revealed
spatiotemporal
signatures
distinct
pathological
functions
N-glycoproteins.
A
comprehensive
resource
experimental
data
from
study
previous
literatures
further
established.
This
atlas
serves
as
a
promising
tool
revealing
role
systems.
Язык: Английский
Recent Advances in Mass Spectrometry-Based Bottom-Up Proteomics
Analytical Chemistry,
Год журнала:
2025,
Номер
unknown
Опубликована: Фев. 25, 2025
Mass
spectrometry-based
proteomics
is
about
35
years
old,
and
recent
progress
appears
to
be
speeding
up
across
all
subfields.
In
this
review,
we
focus
on
advances
over
the
last
two
in
select
areas
within
bottom-up
proteomics,
including
approaches
high-throughput
experiments,
data
analysis
using
machine
learning,
drug
discovery,
glycoproteomics,
extracellular
vesicle
structural
proteomics.
Язык: Английский
Clinical glycoproteomics: methods and diseases
MedComm,
Год журнала:
2024,
Номер
5(10)
Опубликована: Окт. 1, 2024
Abstract
Glycoproteins,
representing
a
significant
proportion
of
posttranslational
products,
play
pivotal
roles
in
various
biological
processes,
such
as
signal
transduction
and
immune
response.
Abnormal
glycosylation
may
lead
to
structural
functional
changes
glycoprotein,
which
is
closely
related
the
occurrence
development
diseases.
Consequently,
exploring
protein
can
shed
light
on
mechanisms
behind
disease
manifestation
pave
way
for
innovative
diagnostic
therapeutic
strategies.
Nonetheless,
study
clinical
glycoproteomics
fraught
with
challenges
due
low
abundance
intricate
structures
glycosylation.
Recent
advancements
mass
spectrometry‐based
have
improved
our
ability
identify
abnormal
glycoproteins
samples.
In
this
review,
we
aim
provide
comprehensive
overview
foundational
principles
recent
glycoproteomic
methodologies
applications.
Furthermore,
discussed
typical
characteristics,
underlying
functions,
diseases,
brain
cardiovascular
cancers,
kidney
metabolic
Additionally,
highlighted
potential
avenues
future
glycoproteomics.
These
insights
provided
review
will
enhance
comprehension
methods
diseases
promote
elucidation
pathogenesis
discovery
novel
biomarkers
targets.
Язык: Английский
Improvements in glycoproteomics through architecture changes to the Orbitrap Tribrid MS platform
Опубликована: Авг. 29, 2024
Hardware
changes
introduced
on
the
Orbitrap
Ascend
MultiOmics
Tribrid
MS
include
dual
ion
routing
multipoles
(IRMs)
that
can
enable
parallelized
accumulation,
dissociation,
and
mass
analysis
of
three
separate
populations.
The
balance
between
these
instrument
functions
is
especially
important
in
glycoproteomics,
where
complexities
glycopeptide
fragmentation
necessitate
large
precursor
populations
and,
consequently,
long
accumulation
times
for
quality
MS/MS
spectra.
To
compound
matters
further,
dissociation
methods
like
electron
transfer
(ETD)
benefit
characterization
come
with
overhead
also
slow
down
scan
acquisition.
Here
we
explored
how
IRM
architecture
improve
analysis,
a
focus
O-glycopeptide
using
ETD
supplemental
collisional
activation
(EThcD).
We
found
parallelization
EThcD
–
uniquely
enabled
by
increased
acquisition
speed
without
sacrificing
spectral
quality,
subsequently
increasing
number
O-glycopeptides
identified
relative
to
analyses
Eclipse
(i.e.,
previous
generation
MS).
Additionally,
systematically
evaluated
ion-ion
reaction
energies
used
understand
best
utilize
time
architecture.
observed
shorter-than-expected
minimized
c/z•-fragment
generation,
higher
collision
generate
combinations
glycan-retaining
glycan-neutral-loss
peptide
backbone
fragments
identification.
saw
improvements
N-glycopeptide
collision-based
faster
speeds.
Overall,
data
show
architectural
platform
glycoproteomic
experiments
parallelizing
minimize
sensitivity.
Язык: Английский
Optimization of glycopeptide enrichment techniques for the identification of clinical biomarkers
Expert Review of Proteomics,
Год журнала:
2024,
Номер
unknown
Опубликована: Окт. 22, 2024
The
identification
and
characterization
of
glycopeptides
through
LC-MS/MS
advanced
enrichment
techniques
are
crucial
for
advancing
clinical
glycoproteomics,
significantly
impacting
the
discovery
disease
biomarkers
therapeutic
targets.
Despite
progress
in
methods
like
Lectin
Affinity
Chromatography
(LAC),
Hydrophilic
Interaction
Liquid
(HILIC),
Electrostatic
Repulsion
(ERLIC),
issues
with
specificity,
efficiency,
scalability
remain,
impeding
thorough
analysis
complex
glycosylation
patterns
understanding.
Язык: Английский
GP-Marker facilitates the analysis of intact glycopeptide quantitative data at different levels
Analytical and Bioanalytical Chemistry,
Год журнала:
2024,
Номер
unknown
Опубликована: Авг. 29, 2024
Язык: Английский
Tools and techniques for quantitative glycoproteomic analysis
Biochemical Society Transactions,
Год журнала:
2024,
Номер
52(6), С. 2439 - 2453
Опубликована: Дек. 10, 2024
Recent
advances
in
mass
spectrometry
(MS)-based
methods
have
significantly
expanded
the
capabilities
for
quantitative
glycoproteomics,
enabling
highly
sensitive
and
accurate
quantitation
of
glycosylation
at
intact
glycopeptide
level.
These
developments
provided
valuable
insights
into
roles
glycoproteins
various
biological
processes
diseases.
In
this
short
review,
we
summarize
pertinent
studies
on
techniques
tools
site-specific
glycoproteomic
analysis
published
over
past
decade.
We
also
highlight
state-of-the-art
MS-based
software
that
facilitate
multi-dimension
quantification
glycoproteome,
targeted
specific
glycopeptides,
isomers.
Additionally,
discuss
potential
applications
these
technologies
clinical
biomarker
discovery
functional
characterization
health
disease.
The
review
concludes
with
a
discussion
current
challenges
future
perspectives
field,
emphasizing
need
more
precise,
high-throughput
efficient
to
further
advance
glycoproteomics
its
applications.
Язык: Английский