In
this
paper,
we
delve
into
the
intricate
realm
of
human
genomics,
presenting
a
novel
design
that
leverages
deep
learning
and
counterfactual
reasoning
for
causal
inference.
We
postulate
mutations
occurring
within
DNA
sequences
have
potential
to
instigate
diseases
by
interrupting
essential
biological
processes,
hypothesis
fundamentally
drives
research.
To
test
this,
undertaken
meticulous
extraction
key
attributes
from
range
databases
hosted
National
Center
Biotechnology
Information
(NCBI).
These
are
subsequently
processed
using
one-hot
encoding,
technique
effectively
transforms
categorical
variables
form
could
be
provided
machine
algorithms.
A
sophisticated
model
is
then
utilized
ascertain
accuracy
hypothesis.
The
output,
depicted
as
graph,
elucidates
relationships
interactions
between
in
question,
providing
graphical
representation
proposed
Our
research
suggests
strategic
modifications
sequence
or
alterations
set
induce
significant
changes
processes.
This,
turn,
can
lead
structure
function
proteins,
cornerstone
cellular
operations.
also
underline
importance
statements
formulating
hypotheses
driving
intelligent
behavior.
Despite
their
untestable
nature
inherent
subjectivity,
these
counterfactuals
serve
powerful
tools
comprehending
predicting
outcomes.
implications
extend
beyond
academic
interest.
It
provides
pathway
deeper
understanding
genomics
holds
promise
development
targeted
therapies
genetic
diseases.
fosters
possibility
personalized
medicine
therapeutic
strategies
alter
course
disease
at
level,
potentially
revolutionizing
healthcare.
Scientific Reports,
Год журнала:
2024,
Номер
14(1)
Опубликована: Окт. 27, 2024
Oral
cancer
(ORCA)
is
the
most
prevalent
histological
subtype
of
oral
malignancies
in
which
immune
modulation
relevant.
The
goal
this
work
was
to
employ
Mendelian
randomization
(MR)
investigate
causal
connection
between
immune-related
proteins
MICB,
CTSA,
MMP9,
and
ORCA.
Open
GWAS
database
Integrative
Epidemiology
Unit
(IEU)
accessed
collect
data
for
ORCA
(ieu-b-4961),
MICB
(prot-a-1898),
CTSA
(prot-a-717)
MMP9
(prot-a-1921).
From
372,373
samples,
dataset
comprises
7,723,107
single
nucleotide
polymorphisms
(SNPs).
all
have
10,534,735
SNPs
3,301
sample
sizes.
Then,
primary
SVMR
implementation
approaches
were
weighted
mode,
simple
inverse
variance
(IVW),
median,
MR-Egger.
IVW
effective
technique.
A
sensitivity
study
also
carried
out
assess
correctness
data,
with
special
focus
devoted
heterogeneity,
horizontal
pleiotropy,
Leave-One-Out
(LOO).
MVMR
eventually
implemented
as
well.
analysis
three
exposure
factors
(ieu-b-94,
ebi-a-GCST012237)
performed
validate
results.
According
results,
there
a
noteworthy
interaction
(P
=
0.0014),
0.0343),
0.0003).
Furthermore,
odds
ratios
(ORs)
values
revealed
that
(OR
1.0005)
an
risk
factor,
whereas
0.9994)
0.9993)
security
factors.
robustness
findings
confirmed
by
p-values
heterogeneity
both
greater
than
0.05.
result
did
not
affect
any
safety
or
hazard
features
these
However,
P
value
0.05,
implying
may
influence
on
MMP9.
validation
outcomes
datasets
harmonized
from
previous
research,
thereby
solidifying
reliability
Our
investigation
provided
crucial
resource
further
research
subject
demonstrating
relationship
International Journal of Oncology,
Год журнала:
2024,
Номер
65(4)
Опубликована: Сен. 5, 2024
Hepatocellular
carcinoma
(HCC)
tissue
is
rich
in
dendritic
cells,
T
B
macrophages,
natural
killer
cells
and
cellular
stroma.
Together
they
form
the
tumor
microenvironment
(TME),
which
also
numerous
cytokines.
Tumor‑associated
macrophages
(TAMs)
are
involved
regulation
of
development.
TAMs
HCC
receive
stimuli
different
directions,
polarize
directions
release
cytokines
to
regulate
development
HCC.
mostly
divided
into
two
cell
phenotypes:
M1
M2.
secrete
pro‑inflammatory
mediators,
M2
a
variety
anti‑inflammatory
pro‑tumorigenic
substances.
The
TAM
polarization
tumors
Both
direct
indirect
methods
for
discussed.
indirectly
support
by
promoting
peripheral
angiogenesis
regulating
immune
TME.
In
terms
between
present
review
mainly
focuses
on
molecular
mechanism.
both
proliferation
apoptosis
quantitative
changes
HCC,
stimulate
related
invasive
migratory
ability
stemness
cells.
aims
identify
immunotherapeutic
options
based
mechanisms
TME
Biocell,
Год журнала:
2024,
Номер
48(1), С. 65 - 78
Опубликована: Янв. 1, 2024
Over
the
past
decade,
swift
advancement
of
metabolomics
can
be
credited
to
significant
progress
in
technologies
such
as
mass
spectrometry,
nuclear
magnetic
resonance,
and
multivariate
statistics.
Currently,
garners
widespread
application
across
diverse
fields
including
drug
research
development,
early
disease
detection,
toxicology,
food
nutrition
science,
biology,
prescription,
chinmedomics,
among
others.
Metabolomics
serves
an
effective
characterization
technique,
offering
insights
into
physiological
process
alterations
in
vivo.
These
changes
may
result
from
various
exogenous
factors
like
environmental
conditions,
stress,
medications,
well
endogenous
elements
genetic
protein-based
influences.
The
potential
scientific
outcomes
gleaned
these
have
catalyzed
formulation
innovative
methods,
poised
further
broaden
scope
this
domain.
Today,
has
evolved
a
valuable
widely
accepted
instrument
life
sciences.
However,
comprehensive
reviews
focusing
on
sample
preparation
analytical
methodologies
employed
within
sciences
are
surprisingly
scant.
This
review
aims
fill
that
gap,
providing
overview
current
trends
recent
advancements
metabolomics.
Particular
emphasis
is
placed
preparation,
sophisticated
techniques,
their
applications
science
research.
Research Square (Research Square),
Год журнала:
2024,
Номер
unknown
Опубликована: Июнь 7, 2024
Abstract
Triple-negative
breast
cancer
(TNBC)
is
recognized
for
its
aggressive
nature,
lack
of
effective
diagnosis
and
treatment,
generally
poor
prognosis.
The
objective
this
study
was
to
investigate
the
metabolic
changes
in
TNBC
using
metabolomics
approaches
explore
underlying
mechanisms
through
integrated
analysis
with
transcriptomics.
In
study,
serum
untargeted
profiles
were
firstly
explored
between
18
21
healthy
controls
(HC)
by
liquid
chromatography-mass
spectrometry
(LC-MS),
identifying
a
total
22
significantly
altered
metabolites
(DMs).
Subsequently,
receiver
operating
characteristic
revealed
that
7-methylguanine
could
serve
as
potential
biomarker
both
discovery
validation
sets.
Additionally,
transcriptomic
datasets
retrieved
from
GEO
database
identify
differentially
expressed
genes
(DEGs)
normal
tissues.
An
integrative
DMs
DEGs
subsequently
conducted,
uncovering
molecular
TNBC.
Notably,
three
pathways—tyrosine
metabolism,
phenylalanine
glycolysis/gluconeogenesis—were
enriched,
explaining
energy
metabolism
disorders
Within
these
pathways,
two
(4-hydroxyphenylacetaldehyde
oxaloacetic
acid)
six
(MAOA,
ADH1B,
ADH1C,
AOC3,
TAT,
PCK1)
identified
critical
components.
summary,
highlights
biomarkers
potentially
be
utilized
screening
comprehensive
transcriptomics
data
provides
validated
in-depth
understanding
metabolism.
Frontiers in Molecular Biosciences,
Год журнала:
2023,
Номер
10
Опубликована: Окт. 23, 2023
Oral
cancer
is
one
of
the
most
common
types.
Many
factors
can
express
certain
genes
that
cause
proliferation
oral
tissues.
Overexpressed
were
detected
in
patients;
three
highly
impacted.
FAP,
FN1,
and
MMP1
targeted
showed
inhibition
results
silico
by
ginsenoside
C
Rg1.
Approved
drugs
retrieved
from
DrugBank
database.
The
docking
scores
show
an
excellent
interaction
between
ligands
macromolecules.
Further
molecular
dynamics
simulations
binding
stability
proposed
natural
products.
This
work
recommends
repurposing
Rg1
as
potential
binders
for
selected
targets
endorses
future
experimental
validation
treatment
cancer.
European Journal Of Oral Sciences,
Год журнала:
2024,
Номер
132(4)
Опубликована: Июнь 3, 2024
Abstract
Colony‐stimulating
factor
2
(CSF2)
plays
a
regulatory
role
in
numerous
cancers.
However,
there
is
needed
to
investigate
the
of
CSF2
oral
squamous
cell
carcinoma
(OSCC)
malignant
phenotype
and
specific
mechanisms
N‐6‐methyladenosine
(m6A)
modification.
Therefore,
we
investigated
mechanism
m6A‐modified
by
WT1‐associated
protein
(WTAP)
OSCC
via
qRT–PCR,
western
blot,
WTAP
overexpression
OSCC.
In
panel
OSCCs,
Kaplan–Meier
plot
analysis
indicated
that
high
expression
was
associated
with
poorer
prognosis.
Cell
functional
experiments
revealed
enrichment
promoted
proliferation
migration
cells
activating
JAK/STAT3
pathway,
whereas
reduced
resulted
decline
blocking
pathway.
This
study
also
confirmed
enhanced
m6A
level
facilitated
silencing
blocked
invasive
reversed
malignancy
induced
overexpression.
Overall,
this
demonstrated
mediates
modification
which
an
oncogenic
development
can
be
target
for
treatment
patients
