Abstract
Background
Detecting
human
cancers
through
cell-free
DNA
(cfDNA)
in
blood
is
a
sensitive
and
non-invasive
option.
However,
capturing
multiple
forms
of
epigenetic
information
remains
technical
financial
challenge.
Methods
To
address
this,
we
developed
multimodal
sequencing
analysis
(MESA),
flexible
approach
to
integrating
diverse
range
features
cfDNA
using
single
experimental
assay,
i.e.,
non-disruptive
bisulfite-free
methylation
sequencing,
such
as
Enzymatic
Methyl-seq.
MESA
enables
simultaneous
inference
four
modalities:
methylation,
nucleosome
occupancy,
fuzziness,
windowed
protection
score
for
regions
surrounding
gene
promoters
polyadenylation
sites.
Results
When
applied
690
samples
from
3
colorectal
cancer
clinical
cohorts,
MESA’s
novel
modalities,
which
include
genomic
features,
including
sites,
improve
detection
beyond
the
traditional
markers
promoter
methylation.
Conclusions
Together,
stands
major
advancement
field
by
utilizing
comprehensive
complementary
profiles
effective
detection.
Liquid
biopsies
enable
early
detection
and
monitoring
of
diseases
such
as
cancer,
but
their
sensitivity
remains
limited
by
the
scarcity
analytes
cell-free
DNA
(cfDNA)
in
blood.
Improvements
to
have
primarily
relied
on
enhancing
sequencing
technology
ex
vivo.
We
sought
transiently
augment
level
circulating
tumor
(ctDNA)
a
blood
draw
attenuating
its
clearance
report
two
intravenous
priming
agents
given
1
2
hours
before
recover
more
ctDNA.
Our
consist
nanoparticles
that
act
cells
responsible
for
cfDNA
DNA-binding
antibodies
protect
cfDNA.
In
tumor-bearing
mice,
they
greatly
increase
recovery
ctDNA
improve
detecting
small
tumors.
Nature Biotechnology,
Год журнала:
2024,
Номер
42(10), С. 1559 - 1570
Опубликована: Янв. 2, 2024
Bisulfite
sequencing
(BS-seq)
to
detect
5-methylcytosine
(5mC)
is
limited
by
lengthy
reaction
times,
severe
DNA
damage,
overestimation
of
5mC
level
and
incomplete
C-to-U
conversion
certain
sequences.
We
present
ultrafast
BS-seq
(UBS-seq),
which
uses
highly
concentrated
bisulfite
reagents
high
temperatures
accelerate
the
~13-fold,
resulting
in
reduced
damage
lower
background
noise.
UBS-seq
allows
library
construction
from
small
amounts
purified
genomic
DNA,
such
as
cell-free
or
directly
1
100
mouse
embryonic
stem
cells,
with
less
higher
genome
coverage
than
conventional
BS-seq.
Additionally,
quantitatively
maps
RNA
(m
Nature Communications,
Год журнала:
2024,
Номер
15(1)
Опубликована: Фев. 28, 2024
No
consensus
strategies
exist
for
prognosticating
metastatic
castration-resistant
prostate
cancer
(mCRPC).
Circulating
tumor
DNA
fraction
(ctDNA%)
is
increasingly
reported
by
commercial
and
laboratory
tests
but
its
utility
risk
stratification
unclear.
Here,
we
intersect
ctDNA%,
treatment
outcomes,
clinical
characteristics
across
738
plasma
samples
from
491
male
mCRPC
patients
two
randomized
multicentre
phase
II
trials
a
prospective
province-wide
blood
biobanking
program.
ctDNA%
correlates
with
serum
radiographic
metrics
of
disease
burden
highest
in
liver
metastases.
strongly
predicts
overall
survival,
progression-free
response
independent
therapeutic
context
outperformed
established
prognostic
factors.
Recognizing
that
ctDNA-based
biomarker
genotyping
limited
low
some
patients,
leverage
the
relationship
between
factors
to
develop
clinically-interpretable
machine-learning
tool
whether
patient
has
sufficient
informative
ctDNA
(available
online:
https://www.ctDNA.org
).
Our
results
affirm
as
an
actionable
provide
practical
framework
optimized
testing.
CA A Cancer Journal for Clinicians,
Год журнала:
2024,
Номер
74(4), С. 368 - 382
Опубликована: Март 22, 2024
Abstract
Multicancer
detection
(MCD)
tests
use
a
single,
easily
obtainable
biospecimen,
such
as
blood,
to
screen
for
more
than
one
cancer
concurrently.
MCD
can
potentially
be
used
improve
early
detection,
including
cancers
that
currently
lack
effective
screening
methods.
However,
these
have
unknown
and
unquantified
benefits
harms.
differ
from
conventional
in
the
organ
responsible
positive
test
is
unknown,
broad
diagnostic
workup
may
necessary
confirm
location
type
of
underlying
cancer.
Among
two
prospective
studies
involving
greater
16,000
individuals,
identified
those
who
had
some
without
recommended
tests,
pancreas,
ovary,
liver,
uterus,
small
intestine,
oropharyngeal,
bone,
thyroid,
hematologic
malignancies,
at
stages.
Reported
sensitivities
range
27%
95%
but
by
are
lower
stage
cancers,
which
treatment
toxicity
would
lowest
potential
cure
might
highest.
False
reassurance
negative
result
reduce
adherence,
risking
loss
proven
public
health
standard‐of‐care
screening.
Prospective
clinical
trials
needed
address
uncertainties
about
accuracy
detect
different
asymptomatic
whether
sufficiently
mortality
reduction,
degree
contribute
overdiagnosis
overtreatment,
work
equally
well
across
all
populations,
appropriate
evaluation
follow‐up
patients
with
test.
