Seminars in Immunopathology,
Год журнала:
2021,
Номер
44(1), С. 137 - 147
Опубликована: Сен. 10, 2021
Genetic
studies,
including
genome-wide
association
have
identified
many
common
variants
that
are
associated
with
autoimmune
diseases.
Strikingly,
in
addition
to
being
frequently
observed
healthy
individuals,
a
number
of
these
shared
across
diseases
diverse
clinical
presentations.
This
highlights
the
potential
for
improved
disease
understanding
which
could
be
achieved
by
characterising
mechanism
lead
increased
risk
disease.
Of
particular
interest
is
identifying
novel
drug
targets
or
repositioning
drugs
currently
used
other
The
majority
do
not
alter
coding
regions
and
it
often
difficult
generate
plausible
hypothetical
affect
disease-relevant
genes
pathways.
Given
this
area,
considerable
effort
has
been
invested
developing
applying
appropriate
methodologies.
Two
most
important
technologies
space
include
both
low-
high-throughput
genomic
perturbation
using
CRISPR/Cas9
system
massively
parallel
reporter
assays.
In
review,
we
introduce
field
functional
genomics
use
numerous
examples
demonstrate
recent
future
impact
technologies.
International Journal of Molecular Sciences,
Год журнала:
2023,
Номер
24(3), С. 2943 - 2943
Опубликована: Фев. 2, 2023
As
an
emerging
sequencing
technology,
single-cell
RNA
(scRNA-Seq)
has
become
a
powerful
tool
for
describing
cell
subpopulation
classification
and
heterogeneity
by
achieving
high-throughput
multidimensional
analysis
of
individual
cells
circumventing
the
shortcomings
traditional
detecting
average
transcript
level
populations.
It
been
applied
to
life
science
medicine
research
fields
such
as
tracking
dynamic
differentiation,
revealing
sensitive
effector
cells,
key
molecular
events
diseases.
This
review
focuses
on
recent
technological
innovations
in
scRNA-Seq,
highlighting
latest
results
with
scRNA-Seq
core
technology
frontier
areas
embryology,
histology,
oncology,
immunology.
In
addition,
this
outlines
prospects
its
innovative
application
Chinese
(TCM)
discusses
issues
currently
being
addressed
great
potential
exploring
disease
diagnostic
targets
uncovering
drug
therapeutic
combination
multiomics
technologies.
Allergy,
Год журнала:
2023,
Номер
78(4), С. 940 - 956
Опубликована: Фев. 2, 2023
Abstract
Asthma
is
a
complex
and
heterogeneous
chronic
inflammatory
disease
of
the
airways.
Alongside
environmental
factors,
asthma
susceptibility
strongly
influenced
by
genetics.
Given
its
high
prevalence
our
incomplete
understanding
mechanisms
underlying
susceptibility,
frequently
studied
in
genome‐wide
association
studies
(GWAS),
which
have
identified
thousands
genetic
variants
associated
with
development.
Virtually
all
these
reside
non‐coding
genomic
regions,
has
obscured
functional
impact
asthma‐associated
their
translation
into
disease‐relevant
mechanisms.
Recent
advances
genomics
technology
epigenetics
now
offer
methods
to
link
gene
regulatory
elements
embedded
within
started
unravel
molecular
(epi)genetics
asthma.
Here,
we
provide
an
integrated
overview
(epi)genetic
asthma,
focusing
on
efforts
associations
biological
insight
pathophysiology
using
state‐of‐the‐art
methodology.
Finally,
perspective
as
how
decoding
epigenetic
basis
potential
transform
clinical
management
predict
risk
Nature,
Год журнала:
2024,
Номер
630(8016), С. 447 - 456
Опубликована: Июнь 5, 2024
Abstract
Increasing
rates
of
autoimmune
and
inflammatory
disease
present
a
burgeoning
threat
to
human
health
1
.
This
is
compounded
by
the
limited
efficacy
available
treatments
high
failure
during
drug
development
2
,
highlighting
an
urgent
need
better
understand
mechanisms.
Here
we
show
how
functional
genomics
could
address
this
challenge.
By
investigating
intergenic
haplotype
on
chr21q22—which
has
been
independently
linked
bowel
disease,
ankylosing
spondylitis,
primary
sclerosing
cholangitis
Takayasu’s
arteritis
3–6
—we
identify
that
causal
gene,
ETS2
central
regulator
macrophages
delineate
shared
mechanism
amplifies
expression.
Genes
regulated
were
prominently
expressed
in
diseased
tissues
more
enriched
for
GWAS
hits
than
most
previously
described
pathways.
Overexpressing
resting
reproduced
state
observed
chr21q22-associated
diseases,
with
upregulation
multiple
targets,
including
TNF
IL-23.
Using
database
cellular
signatures
7
identified
drugs
might
modulate
pathway
validated
potent
anti-inflammatory
activity
one
class
small
molecules
vitro
ex
vivo.
Together,
illustrates
power
genomics,
applied
directly
cells,
immune-mediated
mechanisms
potential
therapeutic
opportunities.
Human Molecular Genetics,
Год журнала:
2021,
Номер
30(R2), С. R187 - R197
Опубликована: Июль 22, 2021
The
application
of
genomics
to
medicine
has
accelerated
the
discovery
mutations
underlying
disease
and
enhanced
our
knowledge
molecular
underpinnings
diverse
pathologies.
As
amount
human
genetic
material
queried
via
sequencing
grown
exponentially
in
recent
years,
so
too
number
rare
variants
observed.
Despite
progress,
ability
distinguish
which
have
clinical
significance
remains
limited.
Over
last
decade,
however,
powerful
experimental
approaches
emerged
characterize
variant
effects
orders
magnitude
faster
than
before.
Fueled
by
improved
DNA
synthesis
and,
more
recently,
CRISPR/Cas9
genome
editing,
multiplex
functional
assays
provide
a
means
generating
effect
data
wide-ranging
systems.
Here,
I
review
applications
that
link
phenotypes
describe
emerging
strategies
will
enhance
their
utility
coming
years.
Human Molecular Genetics,
Год журнала:
2020,
Номер
29(R1), С. R81 - R88
Опубликована: Авг. 3, 2020
Abstract
Whilst
thousands
of
genetic
variants
have
been
associated
with
human
traits,
identifying
the
subset
those
that
are
causal
requires
a
further
‘fine-mapping’
step.
We
review
basic
fine-mapping
approach,
which
is
computationally
fast
and
only
summary
data,
but
depends
on
an
assumption
single
variant
per
region
recognized
as
biologically
unrealistic.
discuss
different
ways
approach
has
built
upon
to
accommodate
multiple
in
incorporate
additional
layers
functional
annotation
data.
methods
for
simultaneous
datasets,
either
exploiting
linkage
disequilibrium
(LD)
structures
across
ancestries
or
borrowing
information
between
distinct
related
traits.
Finally,
we
look
future
opportunities
will
be
offered
by
increasingly
accurate
maps
multitude
Nature Communications,
Год журнала:
2020,
Номер
11(1)
Опубликована: Дек. 8, 2020
Rapidly
advancing
genomic
technologies
and
cross-disciplinary
partnerships
are
accelerating
the
biological
clinical
interpretation
of
genome-wide
association
studies,
with
some
therapies
developed
based
on
these
findings
already
being
tested
in
trials.
The
next
decade
promises
further
progress
understanding
function
genetic
variants.
