Scientific Reports,
Journal Year:
2024,
Volume and Issue:
14(1)
Published: Aug. 6, 2024
The
utility
of
deep
neural
nets
has
been
demonstrated
for
mapping
hematoxylin-and-eosin
(H&E)
stained
image
features
to
expression
individual
genes.
However,
these
models
have
not
employed
discover
clinically
relevant
spatial
biomarkers.
Here
we
develop
MOSBY
(Multi-Omic
translation
whole
slide
images
Spatial
Biomarker
discoverY)
that
leverages
contrastive
self-supervised
pretraining
extract
improved
H&E
features,
learns
a
between
and
bulk
omic
profiles
(RNA,
DNA,
protein),
utilizes
tile-level
information
We
validate
gene
set
predictions
with
transcriptomic
serially-sectioned
CD8
IHC
data.
demonstrate
MOSBY-inferred
colocalization
survival-predictive
power
orthogonal
expression,
enable
concordance
indices
highly
competitive
survival-trained
multimodal
networks.
identify
(1)
an
ER
stress-associated
feature
as
chemotherapy-specific
risk
factor
in
lung
adenocarcinoma,
(2)
the
T
effector
cell
vs
cysteine
signatures
negative
prognostic
multiple
cancer
indications.
discovery
biologically
interpretable
biomarkers
showcases
model
unraveling
novel
insights
biology
well
informing
clinical
decision-making.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2022,
Volume and Issue:
unknown
Published: June 9, 2022
ABSTRACT
Advances
in
artificial
intelligence
have
paved
the
way
for
leveraging
hematoxylin
and
eosin
(H&E)-stained
tumor
slides
precision
oncology.
We
present
ENLIGHT-DeepPT,
an
approach
predicting
response
to
multiple
targeted
immunotherapies
from
H&E-slides.
In
difference
existing
approaches
that
aim
predict
treatment
directly
slides,
ENLIGHT-DeepPT
is
indirect
two-step
consisting
of
(1)
DeepPT,
a
new
deep-learning
framework
predicts
genome-wide
mRNA
expression
(2)
ENLIGHT,
which
based
on
DeepPT
inferred
values.
successfully
transcriptomics
all
16
TCGA
cohorts
tested
generalizes
well
two
independent
datasets.
Importantly,
true
responders
five
patients’
involving
four
different
treatments
spanning
six
cancer
types
with
overall
odds
ratio
2.44,
increasing
baseline
rate
by
43.47%
among
predicted
responders,
without
need
any
data
training.
Furthermore,
its
prediction
accuracy
these
datasets
comparable
supervised
images,
trained
same
cohort
cross
validation.
Its
future
application
could
provide
clinicians
rapid
recommendations
array
therapies
importantly,
may
contribute
advancing
oncology
developing
countries.
Statement
Significance
first
shown
immune
H&E
slides.
distinction
previous
approaches,
it
does
not
require
training
specific
each
drug/indication
but
then
can
further
oncologists
help
advance
underserved
regions
low-income
Cell Reports Medicine,
Journal Year:
2023,
Volume and Issue:
4(12), P. 101313 - 101313
Published: Dec. 1, 2023
Identification
of
the
gene
expression
state
a
cancer
patient
from
routine
pathology
imaging
and
characterization
its
phenotypic
effects
have
significant
clinical
therapeutic
implications.
However,
prediction
individual
genes
whole
slide
images
(WSIs)
is
challenging
due
to
co-dependent
or
correlated
multiple
genes.
Here,
we
use
purely
data-driven
approach
first
identify
groups
with
then
predict
their
status
WSIs
using
bespoke
graph
neural
network.
These
allow
us
capture
small
number
binary
variables
that
are
biologically
meaningful
carry
histopathological
insights
for
cases.
Prediction
based
on
these
allows
associating
histological
phenotypes
(cellular
composition,
mitotic
counts,
grading,
etc.)
underlying
patterns
opens
avenues
gaining
biological
directly.
bioRxiv (Cold Spring Harbor Laboratory),
Journal Year:
2023,
Volume and Issue:
unknown
Published: Sept. 30, 2023
Abstract
Cancer
is
a
heterogeneous
disease
that
demands
precise
molecular
profiling
for
better
understanding
and
management.
Recently,
deep
learning
has
demonstrated
potentials
cost-efficient
prediction
of
alterations
from
histology
images.
While
transformer-based
architectures
have
enabled
significant
progress
in
non-medical
domains,
their
application
to
images
remains
limited
due
small
dataset
sizes
coupled
with
the
explosion
trainable
parameters.
Here,
we
develop
SEQUOIA
,
transformer
model
predict
cancer
transcriptomes
whole-slide
To
enable
full
potential
transformers,
first
pre-train
using
data
1,802
normal
tissues.
Then,
fine-tune
evaluate
4,331
tumor
samples
across
nine
types.
The
performance
assessed
at
individual
gene
levels
pathway
through
Pearson
correlation
analysis
root
mean
square
error.
generalization
capacity
validated
two
independent
cohorts
comprising
1,305
tumors.
In
predicting
expression
25,749
genes,
highest
observed
cancers
breast,
kidney
lung,
where
accurately
predicts
11,069,
10,086
8,759
respectively.
predicted
genes
are
associated
regulation
inflammatory
response,
cell
cycles
metabolisms.
trained
tissue
level,
showcase
its
spatial
patterns
transcriptomics
datasets.
Leveraging
performance,
digital
signature
risk
recurrence
breast
cancer.
deciphers
clinically
relevant
images,
opening
avenues
improved
management
personalized
therapies.
Scientific Reports,
Journal Year:
2024,
Volume and Issue:
14(1)
Published: Aug. 6, 2024
The
utility
of
deep
neural
nets
has
been
demonstrated
for
mapping
hematoxylin-and-eosin
(H&E)
stained
image
features
to
expression
individual
genes.
However,
these
models
have
not
employed
discover
clinically
relevant
spatial
biomarkers.
Here
we
develop
MOSBY
(Multi-Omic
translation
whole
slide
images
Spatial
Biomarker
discoverY)
that
leverages
contrastive
self-supervised
pretraining
extract
improved
H&E
features,
learns
a
between
and
bulk
omic
profiles
(RNA,
DNA,
protein),
utilizes
tile-level
information
We
validate
gene
set
predictions
with
transcriptomic
serially-sectioned
CD8
IHC
data.
demonstrate
MOSBY-inferred
colocalization
survival-predictive
power
orthogonal
expression,
enable
concordance
indices
highly
competitive
survival-trained
multimodal
networks.
identify
(1)
an
ER
stress-associated
feature
as
chemotherapy-specific
risk
factor
in
lung
adenocarcinoma,
(2)
the
T
effector
cell
vs
cysteine
signatures
negative
prognostic
multiple
cancer
indications.
discovery
biologically
interpretable
biomarkers
showcases
model
unraveling
novel
insights
biology
well
informing
clinical
decision-making.