Seven Hub Genes Associated with Huntington’s Disease and Diagnostic and Therapeutic Potentials Identified by Computational Biology
OMICS A Journal of Integrative Biology,
Год журнала:
2025,
Номер
unknown
Опубликована: Март 10, 2025
Huntington's
disease
(HD)
is
characterized
by
progressive
motor
dysfunction
and
cognitive
decline.
Early
diagnosis
new
therapeutic
targets
are
essential
for
effective
interventions.
We
performed
integrative
analyses
of
mRNA
profiles
from
three
microarrays
one
RNA-seq
dataset
the
Gene
Expression
Omnibus
database.
The
datasets
included
were
GSE8762,
GSE24250,
GSE45516,
GSE64810.
Data
pre-processing
background
correction,
normalization,
log2
transformation,
probe-to-gene
symbol
mapping,
differential
expression
analysis.
identified
80
differentially
expressed
genes
(DEGs)
based
on
a
significance
threshold
(p
<
0.05)
absolute
log
fold
change
(logFC)
>0.65.
Additionally,
we
conducted
Ontology
(GO)
pathway
genes.
Protein-protein
interactions
among
DEGs
revealed
network
which
seven
hub
(VIM,
COL1A1,
COL3A1,
COL1A2,
DCN,
CXCR2,
S100A9)
using
cytoHubba
plugin
in
Cytoscape
software.
Two
top
DEGs,
IGHG1
(up-regulated)
PITX1
(up-regulated),
also
hold
potential
as
targets.
Insofar
biological
contextualization
findings
concerned,
enriched
GO
terms
skeletal
system
development,
blood
vessel
vasculature
development.
Molecular
function
highlighted
signaling
receptor
binding,
extracellular
matrix
structural
constituent,
platelet-derived
growth
factor
binding.
Notably,
significant
KEGG
pathways
amoebiasis,
AGE-RAGE
diabetic
complications,
relaxin
pathway.
In
conclusion,
present
computational
biology
multiple
discovered
genes,
shedding
light
molecular
mechanisms
HD.
These
call
translational
clinical
omics
research
may
potentially
lead
to
future
precision
medicine
interventions
novel
diagnostic
biomarkers
Язык: Английский
Elucidating the Impact of Deleterious Mutations on IGHG1 and Their Association with Huntington’s Disease
Journal of Personalized Medicine,
Год журнала:
2024,
Номер
14(4), С. 380 - 380
Опубликована: Апрель 1, 2024
Huntington's
disease
(HD)
is
a
chronic,
inherited
neurodegenerative
condition
marked
by
chorea,
dementia,
and
changes
in
personality.
The
primary
cause
of
HD
mutation
characterized
the
expansion
triplet
repeat
(CAG)
within
huntingtin
gene
located
on
chromosome
4.
Despite
substantial
progress
elucidating
molecular
cellular
mechanisms
HD,
an
effective
treatment
for
this
disorder
not
available
so
far.
In
recent
years,
researchers
have
been
interested
studying
cerebrospinal
fluid
(CSF)
as
source
biomarkers
that
could
aid
diagnosis
therapeutic
development
disorder.
Immunoglobulin
heavy
constant
gamma
1
(IGHG1)
one
CSF
proteins
found
to
increase
significantly
HD.
Considering
this,
it
reasonable
study
potential
involvement
deleterious
mutations
IGHG1
pathogenesis
study,
we
explored
impact
their
subsequent
association
with
We
evaluated
126
single-point
amino
acid
substitutions
structure
functionality
protein
while
exploiting
multiple
computational
resources
such
SIFT,
PolyPhen-2,
FATHMM,
SNPs&Go
mCSM,
DynaMut2,
MAESTROweb,
PremPS,
MutPred2,
PhD-SNP.
sequence-
structure-based
tools
highlighted
10
were
destabilizing.
Subsequently,
out
these
mutations,
eight
variants
(Y32C,
Y32D,
P34S,
V39E,
C83R,
C83Y,
V85M,
H87Q)
identified
pathogenic
phenotype
predictors.
Finally,
two
(Y32C
P34S)
reduce
solubility
protein,
suggesting
propensity
form
aggregates.
These
also
exhibited
higher
residual
frustration
structure.
findings,
hypothesized
may
compromise
its
function
potentially
contribute
pathogenesis.
Язык: Английский