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Deep Learning in Medicine and Computational Biology
Dmytro Fishman
(dmytro@ut.ee)
Cat
Cat
Cat
Representation
Cat
Representation
Cat
Representation
Cat
Cat
Representation
Cat
Not a cat
Machine Learning
http://www.asimovinstitute.org/wp-content/uploads/2016/09/neuralnetworks.png
1.2 million images
1000 categories
Errors
2010
2011
28%
26%
http://karpathy.github.io/2014/09/02/what-i-learned-from-competing-against-a-convnet-on-imagenet/
Errors
2010
2011
2012
28%
26%
16%
http://karpathy.github.io/2014/09/02/what-i-learned-from-competing-against-a-convnet-on-imagenet/
AlexNet (A. Krizhevsky et al. 2012)
Errors
2010
2011
2012
2013
2014
2015
2016
28%
26%
16%
12%
7%
3% <3%
AlexNet (A. Krizhevsky et al. 2012)
http://karpathy.github.io/2014/09/02/what-i-learned-from-competing-against-a-convnet-on-imagenet/
Errors
2010
2011
2012
2013
2014
2015
2016
28%
26%
16%
12%
7%
3% <3%
Hypothetical super-
dedicated fine-
grained expert
ensemble of human
labelers
AlexNet (A. Krizhevsky et al. 2012)
http://karpathy.github.io/2014/09/02/what-i-learned-from-competing-against-a-convnet-on-imagenet/
Errors
2010
2011
2012
2013
2014
2015
2016
28%
26%
16%
12%
7%
3% <3%
Hypothetical super-
dedicated fine-
grained expert
ensemble of human
labelers
AlexNet (A. Krizhevsky et al. 2012)
https://www.semanticscholar.org/paper/Fine-grained-Categorization-Short-Summary-of-our-E-G%C3%B6ring-Freytag/0f3b7d252c236d47cf4185fd81bbb40767baf3d8
Different breeds The same breed
http://thelibertarianrepublic.com/wp-content/uploads/2016/01/self-driving-car1.jpg
http://static.dnaindia.com/sites/default/files/styles/half/public/2016/03/09/435253-skype-translator.jpg?itok=1kAl-u1D
http://static.dnaindia.com/sites/default/files/styles/half/public/2016/03/09/435253-skype-translator.jpg?itok=1kAl-u1D
http://static.dnaindia.com/sites/default/files/styles/half/public/2016/03/09/435253-skype-translator.jpg?itok=1kAl-u1D
https://github.com/deepmind/pysc2
Atari
Starcraft
Go
Dota 2
How about
medical
field?
Medicine is complex
Medicine is really complex
ReconMap 2.0
ReconMap 2.0
Medicine is massive
Deep Learning
Super rapid growth
Deep Learning
Fever
Super rapid growth
Medicine is weird
Bloodletting
Bloodletting
Soothing
Bloodletting Lobotomy
Soothing
Nevertheless…
https://pancreaticcanceraction.org/wp-content/uploads/2012/10/Trends-in-cancer-survival-by-tumour-site-1971_2011.png
Year1970 2010
Trends in cancer survival
Skin
Breast
Prostate
Leukaemia
Bowel
Kidney
Myeloma
Ovarian
Pancreatic
Merck Molecular Activity
Challenge 2012
Diabetic Retinopathy
Development and Validation of a Deep
Learning Algorithm for Detection of Diabetic
Retinopathy in Retinal Fundus Photographs
Dermatologist-level classification of skin
cancer with deep neural networks
Skin Cancer
Development and Validation of a Deep
Learning Algorithm for Detection of Diabetic
Retinopathy in Retinal Fundus Photographs
Dermatologist-level classification of skin
cancer with deep neural networks
Skin Cancer
Diabetic Retinopathy
Diabetic Retinopathy
Diabetic Retinopathy
Diabetic Retinopathy
Diabetic Retinopathy
Diagnostics done manually
9 - 12 minutes per patient
128 175 images for training
128 175 images for training
54 US licensed ophthalmologists
128 175 images for training
54 US licensed ophthalmologists
Classify into healthy, mild
and severe
Sample annotation
1st doctor 2nd doctor 3rd doctor 4th doctor
Healthy Disease
0
0
0
0
1st doctor 2nd doctor 3rd doctor 4th doctor
Healthy Disease
Sample annotation
Healthy Disease
0
1st doctor 2nd doctor 3rd doctor 4th doctor
Sample annotation
Healthy Disease
0 1
4
3
4
1st doctor 2nd doctor 3rd doctor 4th doctor
Sample annotation
Healthy Disease
0
Major vote is used
1
4
3
4
1st doctor 2nd doctor 3rd doctor 4th doctor
Sample annotation
Healthy Disease
0 4
Algorithm might only marginally
outperform doctors
1st doctor 2nd doctor 3rd doctor 4th doctor
Sample annotation
Algorithm vs Ophthalmologists
Algorithm vs Ophthalmologists
Sensitivity,%
100 - Specificity, %
0100
0 100
AUC of 97.4%
Algorithm vs Ophthalmologists
Sensitivity,%
100 - Specificity, %
0100
0 100
AUC of 97.4%
The black curve is ROC
for the Deep Learning
algorithm
Algorithm vs Ophthalmologists
Sensitivity,%
100 - Specificity, %
0100
0 100
AUC of 97.4%
Points on ROC are
performances of
individual
ophthalmologists
The black curve is ROC
for the Deep Learning
algorithm
Performances are very
similar
Algorithm vs Ophthalmologists
Points on ROC are
performances of
individual
ophthalmologists
The black curve is ROC
for the Deep Learning
algorithm
Sensitivity,%
100 - Specificity, %
0100
0 100
AUC of 97.4%
Deep Learning algorithm
can operate in any point
on the curve
Algorithm vs Ophthalmologists
Sensitivity,%
100 - Specificity, %
0100
0 100
AUC of 97.4%
Deep Learning algorithm
can operate in any point
on the curve
Sensitivity,%
100 - Specificity, %
0100
0 100
AUC of 97.4%
Algorithm vs Ophthalmologists
High specificity mode (diagnosis)
Deep Learning algorithm
can operate in any point
on the curve
Sensitivity,%
100 - Specificity, %
0100
0 100
AUC of 97.4%
Algorithm vs Ophthalmologists
High specificity mode (diagnosis)
High sensitivity mode (screening)
Deep Learning algorithm
can operate in any point
on the curve
Sensitivity,%
100 - Specificity, %
0100
0 100
AUC of 97.4%
Algorithm vs Ophthalmologists
High specificity mode (diagnosis)
High sensitivity mode (screening)
While
ophthalmologists’s
mode is fixed by
experience
Diabetic Retinopathy
Development and Validation of a Deep
Learning Algorithm for Detection of Diabetic
Retinopathy in Retinal Fundus Photographs
Dermatologist-level classification of skin
cancer with deep neural networks
Skin Cancer
Development and Validation of a Deep
Learning Algorithm for Detection of Diabetic
Retinopathy in Retinal Fundus Photographs
Dermatologist-level classification of skin
cancer with deep neural networks
Diabetic Retinopathy
Skin Cancer
?!
0 1
0 1
0 1
90% VS 14%
Difference in survival rates is
drastic
0 1
90% VS 14%
129 450
images for
training set
129 450
images for
training set
21 board-
certified
dermatologists
Skin disease
Non-neoplastic
Benign
Malignant
DermalEpidermal Melanocytic
GenodermatosisInflammatory
Epidermal Lymphoma
Melanoma
Dermal
DermalEpidermal Melanocytic
Inflammatory
Epidermal Lymphoma
Melanoma
Dermal
Genodermatosis
Google Inception v3
Google Inception v3
9%
1%
5%
4.5%
8.5% 2% 2%
4% 1.5%
0.5%
1.5%
4.5%
1%
3%
7%
15%
10%
1%3.3%
6.3%
0.4%
4%
5%
9%
1%
5%
4.5%
8.5% 2% 2%
4% 1.5%
0.5%
1.5%
4.5%
1%
3%
7%
15%
10%
1%3.3%
6.3%
0.4%
4%
5%
15%
Sum leaf
nodes
9%
1%
5%
4.5%
8.5% 2% 2%
4% 1.5%
0.5%
1.5%
4.5%
1%
3%
7%
15%
10%
1%3.3%
6.3%
0.4%
4%
5%
15%
13% 8%
10%
5.5%
2%
20%
25%
15%
9%
1%
5%
4.5%
8.5% 2% 2%
4%
0.5%
1.5%
4.5%
1%
3%
7%
15%
10%
1%3.3%
6.3%
0.4%
4%
5%
36%
45%
19%
9%
1%
5%
4.5%
8.5% 2% 2%
4%
0.5%
1.5%
4.5%
1%
3%
7%
15%
10%
1%3.3%
6.3%
0.4%
4%
5%
36%
45%
19%
Algorithm vs Dermatologists
Algorithm vs Dermatologists
Specificity,%
Sensitivity, %
AUC of 96%
Carcinoma:
135 images
Dermatologists (25)
Each of the cases
was verified by
biopsy
Specificity,%
Sensitivity, %
AUC of 96%
Carcinoma:
135 images
Dermatologists (25)
Algorithm vs Dermatologists
Specificity,%
Sensitivity, %
AUC of 96%
Carcinoma:
135 images
Dermatologists (25)
Algorithm vs Dermatologists
Specificity,%
Sensitivity, %
AUC of 96%
Carcinoma:
135 images
Dermatologists (25)
Algorithm vs Dermatologists
Performance of the
algorithm was compared
to dermatologists
Performance of the
algorithm was compared
to dermatologists
Average dermatologist’s
performance was marked
as
Specificity,%
Sensitivity, %
AUC of 96%
Carcinoma:
135 images
Dermatologists (25)
Algorithm vs Dermatologists
Performance of the
algorithm was compared
to dermatologists
Average dermatologist’s
performance was marked
as
Specificity,%
Sensitivity, %
AUC of 96%
Carcinoma:
135 images
Dermatologists (25)
Algorithm vs Dermatologists
Specificity,%
Sensitivity, %
AUC of 96%
Specificity,%
Sensitivity, %
AUC of 94%
Specificity,%
Sensitivity, %
AUC of 91%
Carcinoma:
135 images
Melanoma:
130 images
Melanoma:
111 images
Dermatologists (25) Dermatologists (22) Dermatologists (21)
Algorithm vs Dermatologists
Specificity,%
Sensitivity, %
AUC of 96%
Specificity,%
Sensitivity, %
AUC of 94%
Specificity,%
Sensitivity, %
AUC of 91%
Carcinoma:
135 images
Melanoma:
130 images
Melanoma:
111 images
Dermatologists (25) Dermatologists (22) Dermatologists (21)
Algorithm vs Dermatologists
Across all biopsy verified datasets Deep Neural
Network was superior
Diabetic Retinopathy
Development and Validation of a Deep
Learning Algorithm for Detection of Diabetic
Retinopathy in Retinal Fundus Photographs
Dermatologist-level classification of skin
cancer with deep neural networks
Skin Cancer
https://jamanetwork.com/journals/jama/fullarticle/2588763
https://www.nature.com/nature/journal/v542/n7639/full/
nature21056.html
Few more interesting applications
Diagnosing Parkinson from voice
(Al-Fatlawi et al., 2016)
Detection of hypoglycemic
episodes in children (San et al.,
2016)
HemoglobinA1c
03.2010
Timeline
07.2010
12.2010
02.2011
04.2011
?
Painintensity
Frames
Pain estimation from video
(Zhou et al., 2016)
Predicting subsequent
hospitalisation (Choi et al., 2016)
Sleep
Sleep
Hunger
Sleep
Pain
Hunger
Seems like revolution did not
happened
Why Deep Learning has not
revolutionised medicine yet?
Chart of possible reasons why deep
learning may fail to revolutionise medicineLikelihood
Effect
UnlikelyHighlylikely
Not nice, but ok Terrible consequences
We may fail to compose large
enough datasets
Collecting data in
medicine
is very expensive
We may fail to compose large
enough datasets
Collecting data in
medicine
is very expensive
Medical data is
often protected (for
a good reason)
We may fail to compose large
enough datasets
We may fail to compose large
enough datasets
We may fail to compose large
enough datasets
We may fail to compose large
enough datasets
We can build a model that
can distinguish them from
other objects
We may fail to compose large
enough datasets
We can build a model that
can distinguish them from
other objects
We may fail to compose large
enough datasets
We can build a model that
can distinguish them from
other objects
We cannot build a robust
representation for all of them
We may fail to compose large
enough datasets
We can build a model that
can distinguish them from
other objects
We would need a separate
ImageNet for each type
We may fail to compose large
enough datasets
We cannot build a robust
representation for all of them
http://langlotzlab.stanford.edu/projects/medical-image-net/
http://langlotzlab.stanford.edu/projects/medical-image
Possible solution
http://langlotzlab.stanford.edu/projects/medical-image-net/
Chart of possible reasons why deep
learning may fail to revolutionise medicineLikelihood
Effect
UnlikelyHighlylikely
Not nice, but ok Terrible consequences
Data
How doctors diagnose
melanomas?
There is a ABCD rule
they learned in college
How doctors diagnose
melanomas?
There is a ABCD rule
they learned in college
Melanomas are
Asymmetrical
How doctors diagnose
melanomas?
There is a ABCD rule
they learned in college
Melanomas are
Asymmetrical
How doctors diagnose
melanomas?
There is a ABCD rule
they learned in college
Melanomas are
Asymmetrical
How doctors diagnose
melanomas?
Their Borders
are uneven
There is a ABCD rule
they learned in college
Melanomas are
Asymmetrical
Their Borders
are uneven
How doctors diagnose
melanomas?
There is a ABCD rule
they learned in college
Melanomas are
Asymmetrical
Colour can be
patchy and
variegated
How doctors diagnose
melanomas?
Their Borders
are uneven
There is a ABCD rule
they learned in college
Melanomas are
Asymmetrical
Colour can be
patchy and
variegated
Their Borders
are uneven
How doctors diagnose
melanomas?
There is a ABCD rule
they learned in college
Melanomas are
Asymmetrical
Colour can be
patchy and
variegated
How doctors diagnose
melanomas?
Their Borders
are uneven
There is a ABCD rule
they learned in college
Colour can be
patchy and
variegated
their Diameter is
usually > 6
millimetres
How doctors diagnose
melanomas?
Melanomas are
Asymmetrical
Their Borders
are uneven
There is a ABCD rule
they learned in college
Melanomas are
Asymmetrical
Their Borders
are uneven
Colour can be
patchy and
variegated
their Diameter is
usually > 6
millimetres
How doctors diagnose
melanomas?
How computers diagnose melanomas?
How computers diagnose melanomas?
How computers diagnose melanomas?
Melanoma
How computers diagnose melanomas?
Melanoma
https://arxiv.org/pdf/1708.08296v1.pdf
Chart of possible reasons why deep
learning may fail to revolutionise medicineLikelihood
Effect
UnlikelyHighlylikely
Not nice, but ok Terrible consequences
DataInterpretability
Your computer
Your computer
ACCCTTAAGGAGATCCTT
TAACCGAACCTCACCCTT
AAGGAGATCCTTTAACCG
CCCTTTTATTCCTATTACGT
Read 3.5 B more…
Gene Technology
Your computer
ACCCTTAAGGAGATCCTT
TAACCGAACCTCACCCTT
AAGGAGATCCTTTAACCG
CCCTTTTATTCCTATTACGT
Read 3.5 B more…
Genome
Genome
Schizofrenia - 0.15%
Diabetes - 0.05%
Cancer - 0.01%
Gene Technology
Your computer
ACCCTTAAGGAGATCCTT
TAACCGAACCTCACCCTT
AAGGAGATCCTTTAACCG
CCCTTTTATTCCTATTACGT
Read 3.5 B more…
Risks
Genome
Schizofrenia - 0.15%
Diabetes - 0.05%
Cancer - 0.01%
Gene Technology
Your computer
ACCCTTAAGGAGATCCTT
TAACCGAACCTCACCCTT
AAGGAGATCCTTTAACCG
CCCTTTTATTCCTATTACGT
Read 3.5 B more…
Risks
Genome
Schizofrenia - 0.15%
Diabetes - 0.05%
Cancer - 0.01%
Gene Technology
Your computer
ACCCTTAAGGAGATCCTT
TAACCGAACCTCACCCTT
AAGGAGATCCTTTAACCG
CCCTTTTATTCCTATTACGT
Read 3.5 B more…
Application
Cool company
Risks
Genome
Schizofrenia - 0.15%
Diabetes - 0.05%
Cancer - 0.01%
Gene Technology
Your computer
ACCCTTAAGGAGATCCTT
TAACCGAACCTCACCCTT
AAGGAGATCCTTTAACCG
CCCTTTTATTCCTATTACGT
Read 3.5 B more…
Application
Cool company
Risks
Genome
Schizofrenia - 0.15%
Diabetes - 0.05%
Cancer - 0.01%
Gene Technology
Your computer
ACCCTTAAGGAGATCCTT
TAACCGAACCTCACCCTT
AAGGAGATCCTTTAACCG
CCCTTTTATTCCTATTACGT
Read 3.5 B more…
Risks
Application
Cool company
Risks
Genome
Schizofrenia - 0.15%
Diabetes - 0.05%
Cancer - 0.01%
Gene Technology
Your computer
ACCCTTAAGGAGATCCTT
TAACCGAACCTCACCCTT
AAGGAGATCCTTTAACCG
CCCTTTTATTCCTATTACGT
Read 3.5 B more…
Your computer
ACCCTTAAGGAGATCCTT
TAACCGAACCTCACCCTT
AAGGAGATCCTTTAACCG
CCCTTTTATTCCTATTACGT
Read 3.5 B more…
Encrypting your
genome
Your computer
ACCCTTAAGGAGATCCTT
TAACCGAACCTCACCCTT
AAGGAGATCCTTTAACCG
CCCTTTTATTCCTATTACGT
Read 3.5 B more…
!#$#*(#$@&#$@^@
%#@%@^#@#$*(@#)
$#@&#$@^#@$)@#
$#@*#@$#@####@@!!
Read 3.5 B more…
Encrypting your
genome
Your computer
Encrypted
genome
Gene Technology
!#$#*(#$@&#$@^@
%#@%@^#@#$*(@#)
$#@&#$@^#@$)@#
$#@*#@$#@####@@!!
Read 3.5 B more…
Your computer
#@#$!!@@# - #?@%
#@$(%&&& - ?@#%
$&@))#^%? - ??@%
Encrypted
genome
Gene Technology
!#$#*(#$@&#$@^@
%#@%@^#@#$*(@#)
$#@&#$@^#@$)@#
$#@*#@$#@####@@!!
Read 3.5 B more…
Your computer
Encrypted
risks
#@#$!!@@# - #?@%
#@$(%&&& - ?@#%
$&@))#^%? - ??@%
Encrypted
genome
Gene Technology
!#$#*(#$@&#$@^@
%#@%@^#@#$*(@#)
$#@&#$@^#@$)@#
$#@*#@$#@####@@!!
Read 3.5 B more…
Your computer
Encrypted
risks
#@#$!!@@# - #?@%
#@$(%&&& - ?@#%
$&@))#^%? - ??@%
Encrypted
genome
Gene Technology
!#$#*(#$@&#$@^@
%#@%@^#@#$*(@#)
$#@&#$@^#@$)@#
$#@*#@$#@####@@!!
Read 3.5 B more…
Your computer Decrypt your
risks with your
private key
Encrypted
risks
#@#$!!@@# - #?@%
#@$(%&&& - ?@#%
$&@))#^%? - ??@%
Encrypted
genome
Gene Technology
Your computer Decrypt your
risks with your
private key
Schizofrenia - 0.15%
Diabetes - 0.05%
Cancer - 0.01%
and start
panicking
changing your
lifestyle
Encrypted
risks
#@#$!!@@# - #?@%
#@$(%&&& - ?@#%
$&@))#^%? - ??@%
Encrypted
genome
Gene Technology
Your computer Decrypt your
risks with your
private key
Schizofrenia - 0.15%
Diabetes - 0.05%
Cancer - 0.01%
Chart of possible reasons why deep
learning may fail to revolutionise medicineLikelihood
Effect
UnlikelyHighlylikely
Not nice, but ok Terrible consequences
DataInterpretability
! # $ # * ( # $ @ & # $ @ ^ @ % # @
% @ ^ # @ # $ * ( @ # ) $ # @ & #
$ @ ^ # @ $ ) @ # $ # @ * # @
$#@####@@!!
Read 3.5 B more…
Privacy
Original image
Original image Correct segmentation
Segmentation
Road
Cars
Trees
Original image Correct segmentation
Segmentation
Road
Cars
Trees
Original image Adversarial
example
Original image Correct segmentation
Segmentation
Road
Cars
Trees
Original image Adversarial
example
Altered image
Original image Correct segmentation
Segmentation
Road
Cars
Trees
Original image Adversarial
example
Altered image New funny
segmentation
Chart of possible reasons why deep
learning may fail to revolutionise medicineLikelihood
Effect
UnlikelyHighlylikely
Not nice, but ok Terrible consequences
DataInterpretability
! # $ # * ( # $ @ & # $ @ ^ @ % # @
% @ ^ # @ # $ * ( @ # ) $ # @ & #
$ @ ^ # @ $ ) @ # $ # @ * # @
$#@####@@!!
Read 3.5 B more…
Privacy
Adversarial
attacks
This is all great stuff, what is next?
kaggle.com
http://www.datasciencebowl.com/competitions/turning-machine-intelligence-against-lung-cance
Team: Lauri Listak
Supervisor: Dmytro Fishman
Turning Machine Intelligence
Against Lung Cancer
Turning Machine Intelligence
Against Lung Cancer
http://www.datasciencebowl.com/competitions/turning-machine-intelligence-against-lung-cance
Team: Lauri Listak
Supervisor: Dmytro Fishman
Turning Machine Intelligence
Against Lung Cancer
http://www.datasciencebowl.com/competitions/turning-machine-intelligence-against-lung-cance
Team: Lauri Listak
Supervisor: Dmytro Fishman
20%
of lung cancer deaths
can be reduced with
early detection
High False
Positives rates
lead to interventional
treatments, additional
costs and patient
anxiety
20%
of lung cancer deaths
can be reduced with
early detection
Turning Machine Intelligence
Against Lung Cancer
http://www.datasciencebowl.com/competitions/turning-machine-intelligence-against-lung-cance
Team: Lauri Listak
Supervisor: Dmytro Fishman
2023
github.com/concept-to-clinic/concept-to-
clinic
http://dreamchallenges.org/
References
• Series of blog posts “Do machines actually beat doctors?” by
Luke Oakden-Rayner (https://lukeoakdenrayner.wordpress.com/
2016/11/27/do-computers-already-outperform-doctors/)
• Opportunities and obstacles for deep learning in biology and
medicine by Ching et al. (http://www.biorxiv.org/content/biorxiv/
early/2017/05/28/142760.full.pdf)
• Computational biology - deep learning by William Jones, Kaur
Alasoo, Dmytro Fishman et al. (accepted)
Contact: dmytro@ut.ee

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