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Chapter

Applications of Machine Learning

in Healthcare
Christopher Toh and James P. Brody

Abstract

Machine learning techniques in healthcare use the increasing amount of health

data provided by the Internet of Things to improve patient outcomes. These
techniques provide promising applications as well as significant challenges. The
three main areas machine learning is applied to include medical imaging, natural
language processing of medical documents, and genetic information. Many of
these areas focus on diagnosis, detection, and prediction. A large infrastructure
of medical devices currently generates data but a supporting infrastructure is
oftentimes not in place to effectively utilize such data. The many different forms
medical information exist in also creates some challenges in data formatting and
can increase noise. We examine a brief history of machine learning, some basic
knowledge regarding the techniques, and the current state of this technology in
healthcare.

Keywords: machine learning, healthcare, big data, medicine, genetics, disease

1. Introduction

The advent of digital technologies in the healthcare field is characterized by

continual challenges in both application and practicality. Unification of disparate
health systems have been slow and the adoption of a fully integrated healthcare
system in most parts of the world has not been accomplished. The inherent nature
and complexity of human biology, as well as the variation between individual
patients has consistently shown the importance of the human element in diagnos-
ing and treating diseases. However, advances in digital technologies are no doubt
becoming indispensable tools for healthcare professionals in providing the best care
for patients.
The improvement of data technologies, including storage size, computational
power, and data transfer speeds, has enabled the widespread adoption of machine
learning in many fields—healthcare included. Due to the multivariate nature of
providing quality healthcare to an individual, the recent trends in medicine have
emphasized the need for a personalized medicine or “precision medicine” approach
to healthcare. The goal of personalized medicine is to use large amounts of health-
care data to find, predict, and analyze diagnostic decisions, which physicians can in
turn implement for each individual patient. Such data includes but is not limited to
genetic or familial information, medical imaging data, drug combinations, popula-
tion wide patient health outcomes, and natural language processing of existing
medical documentation.

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Smart Manufacturing - When Artificial Intelligence Meets the Internet of Things

We will focus primarily on three of the largest applications of machine learning

(ML) in the medical and biomedical fields. As a rapidly evolving field, there is a
wide range of potential applications of machine learning in the healthcare field
which may encompass auxiliary aspects of the field such as personnel management,
insurance policies, regulatory affairs, and much more. As such, the topics covered
in this chapter have been narrowed down to three common applications of machine
learning.
The first is the use of machine learning in medical images such as magnetic reso-
nance imaging (MRIs), computerized axial tomography (CAT) scans, ultrasound
(US) imaging, and positron emission tomography (PET) scans. The result of these
imaging modalities is a set or series of images which typically requires a radiologist
to interpret and make a diagnosis. ML techniques have rapidly been advancing to
predict and find images which may indicate a disease state or serious issue.
The second is natural language processing of medical documents. With the
push towards electronic medical records (EMR) in many countries, the consensus
from many healthcare professionals has been that the process is slow, tedious,
and, in many cases, completely botched. This can sometimes lead to poorer overall
healthcare for patients. One of the major challenges is the amount of physical medi-
cal records and documentation that already exists in many hospitals and clinics.
Different formatting, hand-written notes, and a plethora of incomplete or non-
centralized information has made the switch to adopting electronic medical records
less than efficient.
The third machine learning application encompasses the use of human genetics
to predict disease and find causes of disease. With the advent of next-generation
sequencing (NGS) techniques and the explosion of genetic data including large
databases of population-wide genetic information, the attempt to discern meaning-
ful information of how genetics may affect human health is now at the forefront of
many research endeavors. By understanding how complex diseases may manifest
and how genetics may increase or decrease an individual person’s risk can aid in
preventative healthcare. This could provide physicians with more information
on how to tailor a specific patients’ care plan to reduce the risk of acquiring more
complex diseases.
The common issue present in all three of these topics is how to translate health
data acquired from the Internet of Things, into understandable, useful, trustworthy
information for patients and clinician. How do we interpret hundreds of thousands
of inputs and parameters from the data? How do we do this efficiently? What is the
progress of addressing this problem currently?

2. Artificial intelligence and machine learning

Artificial intelligence (AI) has been intricately linked to the rise of modern-day
computing machines. Machine learning has its roots and beginnings firmly planted
in history. Alan Turing’s work in cracking the German Enigma machine during
World War II became the basis for much of modern computer science. The Turing
Test, which aims to see if AI has become indistinguishable from human intelligence,
is also named after him [1, 2].
At the height of the Second World War, the Allies had a significant logistical
hurdle in the Atlantic. The United States and United Kingdom needed to set up
secure shipping lines to move both armaments and troops to England in preparation
for a mainland European invasion. However, the German U-boats were extremely
effective at disrupting and sinking many of the ships traversing these shipping lanes
[3]. As such, the Allies needed to intercept German communications to swing the

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Battle of the Atlantic in their favor. The Germans encrypted their communications
with The Enigma Machine, the most sophisticated encryption device of its time.
Turing and the rest of Bletchley Park were tasked with breaking the coded
messages produced by The Enigma Machine and eventually produced The Bombe,
a mechanical computing device which successfully decoded the cipher of The
Enigma machine (Figure 1). Using the Bombe, they read the German orders sent to
submarines and navigated their ships around these dangers. This was Turing’s first
intelligent machine. Alan Turing would later go on to describe the idea of a thinking
machine which would eventually be called AI [4].
Machine learning is a subset of AI and the term was coined in the late 1950s by
Arthur Samuel who published a paper on training computers to play checkers when
he worked with IBM [5]. AI is best described as giving human-like intelligence to
machines in a manner that directly mimics the decision making and processing of
the human conscience. ML is the subset of AI that focuses on giving machines the
ability to learn in an unaided manner without any human intervention.
By the late 1960s, researchers were already trying to teach computers to play
basic games such as tic-tac-toe [6]. Eventually, the idea of neural networks,
which were based on a theoretical model of human neuron connection and com-
munication, was expanded into artificial neural networks (ANNs) [7, 8]. These
foundational works laid dormant for many years due to the impracticality and poor
performance of the systems created. Computing technology had not yet advanced
enough to reduce the computational time to a practical level.
The modern computer era led to exponential increases in both computational
power and data storage capacity. With the introduction of IBM’s Deep Blue and
Google’s AlphaGo in recent decades, several leaps in AI have shown the capacity of

Figure 1.
Picture of the German Enigma machine which was used to code military communications. Taken from
Wikimedia Commons.

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Smart Manufacturing - When Artificial Intelligence Meets the Internet of Things

AI to solve real world, complex problems [9, 10]. As such, the promise of machine
learning has taken hold in almost every sector imaginable.
The widespread adoption of machine learning can be mostly attributed to the
availability of extremely large datasets and the improvement of computational
techniques, which reduce overfitting and improve the generalization of trained
models. These two factors have been the driving force to the rapid popularization
and adoption of machine learning in almost every field today. This coupled with the
increasing prevalence of interconnected devices or the Internet of Things (IoT) has
created a rich infrastructure upon which to build predictive and automated systems.
Machine learning is a primary method of understanding the massive influx of
health data today. An infrastructure of systems to complement the increasing IoT
infrastructure will undoubtedly rely heavily on these techniques. Many use cases
have already show enormous promise. How do these techniques work and how do
they give us insight into seemingly unconnected information?

2.1 Machine learning algorithms

Machine learning is broadly split into supervised and unsupervised learning.

Algorithms falling under both categories implement mathematical models. Each
algorithm aims to give computers the ability to learn how to perform certain tasks.

2.1.1 Supervised learning

Supervised learning typically employs training data known as labeled data.

Training data has one or more inputs and has a “labeled” output. Models use these
labeled results to assess themselves during training, with the goal of improving the
prediction of new data (i.e., a set of test data) [11]. Typically, supervised learning
models focus on classification and regression algorithms [12]. Classification prob-
lems are very common in medicine. In most clinical settings, diagnosing of a patient
involves a doctor classifying the ailment given a certain set of symptoms. Regression
problems tend to look at predicting numerical results like estimated length of stay
in a hospital given a certain set of data like vital signs, medical history, and weight.
Common algorithms included in this supervised learning group are random for-
ests (RF), decision trees (DT), Naïve Bayes models, linear and logistic regression,
and support vector machines (SVM), though neural networks can also be trained
through supervised learning [13]. Random forests are a form of decision trees but
are an ensemble set of independently trained decision trees. The resulting predic-
tions of the trees are typically averaged to get a better end result and prediction
[14]. Each tree is built by using a random sample of the data with replacement and
at each candidate split a random subset of features are also selected. This prevents
each learner or tree from focusing too much on apparently predictive features of the
training set which may not be predictive on new data. In other words, it increases
generalization of the model. Random forests can have hundreds or even thousands
of trees and work fairly well on noisy data [15]. The model created from aggregat-
ing results from multiple trees trained on the data will give a prediction that can be
assessed using test data (Figure 2).
A method used to improve many supervised algorithms is known as gradient
boosting. Taking decision trees as an example, the gradient boosting machine as it
is commonly known, performs a similar ensemble training method as the random
forest but with “weak learners.” Instead of building the decision trees in parallel as
in the random forest algorithm, the trees are built sequentially with the error of the
previous tree being used to improve the next tree [16]. These trees are not nearly
as deep as the random forest trees, which is why they are called “weak” (Figure 3).

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Figure 2.
Example of a workflow for training and assessing a random forest model. Each green triangle represents an
independently trained tree from the training data. The prediction of each tree is summed and is represented
as the model. Test data is then fed to the model, i.e., all the trees, and the resulting prediction is made. The
prediction is then compared to the original test data to assess how the model performs.

Typically, better results can be achieved with gradient boosting, but tuning is much
more difficult, and the risk of overfitting is higher. Gradient boosting works well
with unbalanced data and training time is significantly faster due to the gradient
descent nature of the algorithm [17, 18].

2.1.2 Unsupervised learning

Unsupervised machine learning uses unlabeled data to find patterns within

the data itself [19]. These algorithms typically excel at clustering data into rel-
evant groups, allowing for detection of latent characteristics which may not be

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Smart Manufacturing - When Artificial Intelligence Meets the Internet of Things

Figure 3.
Example of a simple workflow for training and assessing a gradient boosting machine model. Each green
triangle represents a trained tree from the training data with the subsequent tree using the residuals or errors
from the prior tree to improve its prediction. The prediction of each tree is summed and is represented as the
model. Test data is then fed to the model, i.e., all the trees, and the resulting prediction is made. The prediction
is then compared to the original test data to assess how the model performs.

immediately obvious. However, they are also more computationally intensive and
require a larger amount of data to perform.
The most common and well-known algorithms are K-means clustering and deep
learning, though deep learning can be used in a supervised manner [12, 20]. Such
algorithms also perform association tasks which are similar to clustering. These
algorithms are considered unsupervised because there is no human input as to what
set of attributes the clusters will be centered on.
The typical k-means algorithm has several variations such as k-medians and
k-medoids, however the principle is the same for each algorithm. The algorithm
uses Euclidian distance to find the “nearest” center or mean for a cluster assuming
there are k clusters. It then assigns the current data point to that cluster and then

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recalculates the center for the cluster, updating it for the next data point [21]. The
biggest drawback to this algorithm is that it must be initialized with an expected
number of “means” or “centers.” Improper selection of the k value can result in poor
clustering.
Deep learning uses neural nets to perform predictions even on unlabeled data as
well as classification techniques. Based off models of human neurons, perceptrons,
as they are typically called, are organized into many networked layers making the
network “deep” in nature [20]. Each perceptron has multiple inputs and a single
output. They are organized into layers where the outputs of the previous layer
serve as the inputs for the next layer. The input layer requires one perceptron
per input variable and the subsequent layers are determined before training by
a human (Figure 4). This is one of the difficulties and challenges in building an
effective neural net. The computationally intensive nature of computing each
perceptron for a large neural net can mean that training alone can take days to
weeks for large data sets [22].

2.1.3 Hyperparameters

In machine learning, a model typically has a set of parameters as well as a set of

hyperparameters. Parameters are variables about the model that can be changed
during training. For example, parameters can be the values of the training data
itself with each piece of data being different along one or several of the parameters.
Whereas hyperparameters are typically set before training occurs and cannot
change once learning begins. Hyperparameters typically are set to tune values like
the model’s learning speed and constrain the algorithm itself.
Different algorithms will have different sets of hyperparameters. For example,
a common hyper parameter for artificial neural networks is the number of hidden
layers. Additionally, a separate but related hyperparameter is the number of per-
ceptrons in each hidden layer. Whereas a similar equivalent in decision trees would

Figure 4.
Example of a simple neural net with two hidden layers of three perceptrons each. The number of inputs,
number of hidden layers, and number of perceptrons in each layer can be changed. Additionally, the
connections between layers and perceptrons can also be changed.

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Smart Manufacturing - When Artificial Intelligence Meets the Internet of Things

be the maximum number of leaves in a tree or the maximum depth for a tree. Other
common hyperparameters include learning rate, batch size, dropout criterion, and
stopping metric.
Properly selecting hyperparameters can significantly speed up the search for
a proper generalized model without sacrificing performance. However, in many
cases finding the proper set is more of an art than a science. Many researchers have
attempted to make hyperparameter searching a more efficient and reproducible
task [23–25]. Again, this process also highly depends on the algorithm, dataset, and
problem you are trying to solve. A machine learning model can be tuned a nearly
infinite amount of different ways to achieve better performance. Hyperparameters
represent a way to reproduce results and also serve as a tool to properly vali-
date models.

2.1.4 Algorithm principles

Considering the pace of research in the field, there are constant advances
and improvements to many of these machine learning techniques, but the
important thing to remember is that not all algorithms work for all use cases.
Each algorithm has advantages and disadvantages. Certain data types may also
affect the performance of individual algorithms and the time spent implement-
ing such models will often be a result of testing different variations, parameters,
and hyperparameters within these algorithms to achieve the best generalized
performance.

2.2 Assessment of model performance

The goal of any machine learning algorithm is to utilize real data to create a
model that performs the best on real-world scenarios, and that can be assessed in
a quantitative, reproducible manner. Assessment of statistical models is a whole
subfield in itself, but we will briefly discuss the basics, which are applicable for
almost any machine learning algorithm you will come across.

2.2.1 Sensitivity vs. specificity

Sensitivity and specificity are two important metrics used in a statistical or

machine learning model to assess if the model is performing successfully. As such, it
is important to understand what each of these numbers tell us about what a trained
model can do, and what the model cannot do.
Sensitivity is the probability that a positive result occurs given that the sample is
indeed positive. Mathematically,
(Number of True Positives)
Sensitivity = _______________________________________
Number of True Positives + Number of False Negatives

This is also sometimes referred to as the recall or hit rate, or just simply the true
positive rate, and the sensitivity is equivalent to 1 − False Negative Rate.
Specificity is the probability of a negative result given that the sample is nega-
tive. Mathematically,
Number of True Negatives
Specificity = _______________________________________
Number of True Negatives + Number of False Positives

This value is also referred to as the selectivity of the test. This is equivalent to
1 − False Positive Rate.

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2.2.2 The receiver operator curve and area-under the curve

The standard metric for assessing the performance of machine learning

models is known as the receiver operating characteristic (ROC). The ROC can be
summarized by a number from 0 to 1, which is the measured area-under-the-ROC
curve (AUC). The ROC curve is a 2D plot that measures the false positive rate vs.
true positive rate. There are four numbers that are used to determine the effective-
ness of a test: true positive rate, false positive rate, true negative rate, and false
negative rate.
True positive and true negative are the correct answers to a test while false posi-
tive and false negative are incorrect answers to the test or model. These numbers
can be condensed further into two numbers known as sensitivity and specificity.
We have already discussed sensitivity and specificity but now we will discuss how
they are used to create the ROC.
Ideally a test would have both high sensitivity and high specificity. However,
there is a tradeoff, prioritizing one often leads to the detriment of the other. When
setting the threshold low, one will receive a high true positive rate (high sensitivity)
and a high false positive rate (low specificity). Conversely, setting the threshold
high will result in a low true positive rate (low sensitivity) and a low false positive
rate (high specificity).
The ROC and AUC metric is used to characterize most of the classification tasks
many machine learning models are attempting to do; does this person have the
disease or do they not? If a test has a high sensitivity and a high specificity it is con-
sidered a near perfect test and the AUC is close to 1 (Figure 5). If the test is random
then the AUC is 0.5. The x-axis is typically the false positive rate (or 1 – specificity).
Ideally, the false positive rate is as low as possible. The y-axis is typically the true
positive rate (sensitivity). The sensitivity is what is usually maximized. On a typical
curve, the midpoint of the curve is the most balanced trade-off between sensitiv-
ity and specificity though this is not always the case. The AUC value is a simpler,
more generalized way, to assess the performance rather than the varying tradeoffs
between sensitivity and specificity.
Another way to think of AUC is as a percentage the model can correctly identify
and separate a positive result from a negative result. Given an unknown case, a
model with an AUC of 0.75 has a 75% chance of correctly identifying whether the
case is a positive case or a negative case. This number will quickly tell you the results
of any model.

2.2.3 Overfitting

Overfitting is one of the main concerns when training any model [26]. Simply
put, when training a model on a set of data, over-training the model will improve
the performance of the model on that specific dataset but at the cost of losing
generalization to other datasets. An overfitted model will not work when applied to
new data it has never seen before. From a practical standpoint, such a model is not
very useful in a real-world application.
When training any machine learning model, the ideal result is a generalized
model. A generalized model works well on a variety of different cases and a vari-
ety of different datasets, especially data it has never seen before. As such, many
researchers are hesitant to give too much credence to a model or method that utilizes
a single dataset.
A variety of methods have been used to prevent models from overfitting and
many of these are now encapsulated in the hyperparameters discussed earlier.

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Smart Manufacturing - When Artificial Intelligence Meets the Internet of Things

Figure 5.
Examples of an AUC denoting a model which has good predictive power (left) and an AUC denoting a model
with poor or near random predictive power (right). 1 – Specificity is sometimes written as false positive rate
( fpr) and sensitivity can be read as true positive rate (tpr).

The idea is to prevent the models from adapting too quickly to the dataset it is being
trained on. This subset of methods is known as regularization [27].
One such method, used in neural nets, is called dropout. This method is widely
used to prevent artificial neural nets from overfitting during classification tasks.
The method is fairly simple. During the training process, random perceptrons and
their corresponding connections are “dropped” from the network. These “thinned”
networks have better performance compared to other regularization techniques on
supervised learning tasks [28].
Often a method known as cross-validation is used to assess the performance and
validate the generalized predictive ability of a model. The most common method for
building machine learning models is the partitioning of the data set into roughly
80% for training and 20% for testing. This partition is typically less useful for linear
models but splitting is more beneficial for complex models [29]. During cross-val-
idation, this split is done in separate sections of the data to ensure proper coverage.
For example, if a 10-fold cross-validation is performed, the first split in a data set
with 100 observations could be a the first 80 for training and the last 20 for test, the
second split could be the first 10 and last 10 for test and the middle 80 for training,
etc. (Figure 6). This creates 10 models using the same algorithm just trained and
tested on different portions of the same data. The average performance of these 10
models gives a good measurement of the generalized performance of the algorithm
on that type of data.

2.3 Big data and the health information explosion

The healthcare sector has always had a very large amount of information, often
times stored as physical documents in clinics, hospitals, regulatory agencies, and
biomedical companies [30, 31]. With the push to electronic medical records (EMR),
this information is rapidly being transformed into a form which can be leveraged
by AI technologies. The estimated amount of healthcare data stored in 2011 was
around 150 exabytes (1 EB = 1018 bytes), though that number is most likely expo-
nentially larger almost a decade later [32, 33]. These large databases, when in a
digitized form, are often known as Big Data.
However, such healthcare information is very different in both form and func-
tion. Visual data in the form of medical images is very different than familial history

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Figure 6.
Example of a set of cross validation splits. There are n splits for the number of iterations desired and the results
of all iterations are averaged to assess the generalized performance of a model trained on a dataset.

which may be simple text-based information. Laboratory and clinical tests may be
reported as numbers only, while health outcomes are often qualitative in nature
and may be a simple yes or no entry in a spreadsheet. Insurance and administrative
data is also indirectly linked to various information, such as patient outcomes, while
information from sensor based technologies like EKGs, pulse oximeters, and EEG
provide time-series data of vital signs [34].
Additionally, the genomic revolution has contributed enormously to the data
explosion. Large-scale genetic databases such as the Cancer Genome Atlas (TCGA)
and the UK Biobank include thousands of patients’ genetic sequencing information
along with various other health information such as disease state, age of diagnosis,
time of death, and much more [35–38]. Copy number variation (CNV) data from
the UK Biobank’s roughly 500,000 patients, which does not even contain the raw
sequence reads, is almost 2 Terabytes (TB) alone in flat text files. These genetic
databases rely on an array of assays and sequencers spread across different hospitals

Database Size of data Number of Status Start

participants date
The Cancer Genome Atlas 2.5 petabytes 11,300 [36, 41] Completed 2005
* +
The UK Biobank ~26 terabytes , ~488,377 [42] Ongoing 2006
*
The European Prospective Unclear ~521,000 [43] Ongoing 1992
Investigation into Cancer
and Nutrition (EPIC)

Estonian Genome Project Unclear* ~52,000 [44] Ongoing 2007

*
deCODE Unclear ~160,000 [45, 46] Ongoing 1998

China Kadoorie Biobank Unclear* ~510,000 [47, 48] Ongoing 2004

*
Lifelines Cohort Study Unclear ~167,000 [49] Ongoing 2006

All of Us (Precision Unclear* Currently ~10,000, Ongoing 2015

Medicine Initiative) planned 1,000,000
[12, 50–52]

FinnGen Unclear* Planned 500,000 [53] Ongoing 2017

*Project is continuing to collect more data.
+
Number represents genetic data only. Project or study may also include unreported data including medical images
and health records.

Table 1.
Overview of largest biobank databases as of 2019.

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Smart Manufacturing - When Artificial Intelligence Meets the Internet of Things

and research facilities around the globe, before being processed and transferred to
their respective centralized storage databases [35, 39, 40].
The collection of biological data and creation of these databases show no
evidence of slowing down. Many biobanks, databases which contain some form
of biological samples such as blood or serum, contain thousands of participants
and many have plans to collect hundreds of thousands of samples from patients
(Table 1). Because many databases are growing so quickly it is unclear how much
data resides in many of these databases. However, The Cancer Genome Atlas alone
contains 2.5 petabytes (1 PB = 1015 bytes) of data and the UK Biobank contains 26
terabytes (1 TB = 1012 bytes) of just genetic information (UK Biobank also contains
medical images such as brain scans which is not included in this table).
Implementing machine learning systems into a hospital with this complex
information Web is usually slow, due to the abundance of caution needed to ensure
patient health. Many physicians are also wary of adopting new systems that are
unproven in a clinical setting due to the risk of litigation and potentially cata-
strophic consequences for their patients.

3. Machine learning of medical images

Modern medical images are digital in nature. To effectively utilize them in

healthcare there are several challenges that must be overcome. Medical imaging
describes a collection of techniques to create visual representations of interior
portions of the human body for the purpose of diagnosis, analysis, and medi-
cal intervention. This is beneficial in avoiding or reducing the need for the older
clinical standard of exploratory surgery. Since opening any portion of the human
body through surgical means increasing the risk of infections, strokes, and other
complications, medical imaging is now the preferred tool for initial diagnosis in the
clinical setting.
The current clinical standard of assessing medical images is the use of trained
physicians, pathologists, or radiologists who examine the images and determine the
root cause of clinical ailments. This clinical standard is prone to human error and is
also costly and expensive, often requiring years or decades of experience to achieve
a level of understanding which can consistently assess these images. Considering
that the demonstration of viable machine learning capabilities in the modern age
was demonstrated by Andrew Ng using images pulled from YouTube videos, it is
clear why medical images were one of the first areas addressed during the initial
adoption of machine learning techniques in healthcare [54].
Accuracy of diagnosis is extremely important in the medical field as improper
diagnosis could lead to severe consequences and results. If a surgery is performed
where none was needed or a misdiagnosis leads to improper dosages of prescribed
medication, the possibility of a fatal outcome increases. In the realm of image pro-
cessing, most techniques rely fundamentally on deep learning (DL) and specifically
in artificial neural networks (ANNs). Modern techniques utilize improvements to
ANNs in the form of convolutional neural networks (CNNs) to boost performance
when classifying images.
The majority of the current publications are using some form of CNNs when it
comes to object detection in medical images [55]. Graphic-processing unit (GPU)
acceleration has made the building of deep CNNs more efficient, however signifi-
cant challenges in creating a competent model still exist. The biggest issue is the
need for a large amount of annotated medical image data. The cost to aggregate and
create such databases is often prohibitive since it requires trained physicians’ time to
annotate the images. Additionally, concerns involving patient privacy often hinders

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the ability to make such databases open-source. Many studies only use around
100–1000 samples in training CNNs. This limited sample size increases the risk of
overfitting and reduces the accuracy of the predictions [56].
Concerns regarding the implementation of machine learning into clinical diagno-
sis have been raised regarding proper validation of models [57]. The main fears entail
properly scoping the intended goals of a machine learning model, reducing dimen-
sionality of the data, and reproducibility of training such models on real-world and
new clinical data. Validating results on other datasets can be difficult due to the lack
of larger datasets for niche diseases, where the aggregation of this data can take more
work than the actual training of the model. Medical imaging data is inherently more
difficult to acquire and is more difficult to store and process. The infrastructure to
handle the data has simply not kept up with the increase in the amount of data.

3.1 Lesion detection and computer automated detection

The most common use of current machine learning technologies in medicine

is for computer automated detection (CAD) specifically in the detection of lesions
such as those commonly found in mammograms, brain scans, and other body scans
[58]. These methods use CNNs to arrive at the probability that a candidate lesion is
in fact a lesion, often utilizing several 2D slices of 3D rotational scans of either CAT
or MRI images.
Ultrasound images are also used in training and a variety of methods such as
randomized rotation of the images or centering candidate lesions in the center of
the image. Especially in mammography, CAD techniques have reached a level where
they are used as a “second opinion” for most radiologists, greatly improving the
accuracy of screenings without doubling the cost associated with using a human as
the “second opinion” Figure 7.
CAD is also currently split into detection and diagnosis. This distinction is subtle
but important. A lesion can be categorized as either benign or malignant, based off
a physician’s knowledge and assessment. However, the actual detection is a crucial
first step in treating a patient.

Figure 7.
Example of mammogram with the left image being that of a raw mammogram and the right hand being the
image with the detection overlaid with the region of interest in white, using NASA software originally used to
enhance earth science imagery. Taken from NASA press release, credited to Bartron Medical Imaging.

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Smart Manufacturing - When Artificial Intelligence Meets the Internet of Things

Computer aided detection is the actual recognition of potential lesions from a

medical image. For example, detection and segmentation of glioblastoma is a dif-
ficult task, due to the invasive and widespread nature of these tumors. Unlike other
brain tumors, they are not easily localized and assessing how treatments such as
chemotherapy are performing is in itself a difficult task. Deep learning has aided in
this by helping automate assessment of glioblastoma MRIs [59].
Computer aided diagnosis describes the probability a lesion is malignant in
nature. These methods are primarily used to improve the accuracy of diagnosis and
improve early diagnosis in the clinical setting. Again, these tasks have consistently
been performed by machine learning especially in brain related applications, due to
the difficult nature of assessing brain health. Additionally, diagnosis of Alzheimer’s
through medical imaging is a possible application for deep learning which is show-
ing some promise [60, 61].

4. Natural language processing of medical documents and literature

Electronic medical records (EMR), the new standard in many hospitals, require
complex digital infrastructure. Unification of health data in a formatted manner is a
major goal as it should increase the efficiency of hospitals as well as improve patient
health outcomes. However, a significant problem is the historical existing physical
documentation. Transferring these existing documents into an electronic form is
difficult and would be very tedious and expensive if people were hired to manually
input such information into an electronic system.
One application of machine learning, which may aid in this problem, is natural
language processing (NLP). By scanning these documents rapidly and integrating
the resulting images into a database, these systems attempt to extract readable data
from free text and incorporates image processing to identify key words and terms.
Handwritten physician notes contain information such as patient complaints, the
physicians own observations, and patient family history. This clinical information
can be annotated. However, poorly worded or inaccurate writing by the physician
can make it difficult to accurately assign this information to appropriate categories.
Forms and documents that already have structure make for much easier language
processing, though there is still the risk of missing data Figure 8.
Creating a system for improved clinical decision support (CDS) with old patient
records is feasible. Any such system is structured to aid in clinical decision making
for individual patients based on a database of computerized knowledge. Such a
system could be envisioned as two-fold: 1. extracting facts about the patient from
their medical record, either through written or typed physician notes or labs or dic-
tation involving audio NLP, 2. Associating possible disease states based on extracted
information from previous known cases or through literature search via NLP [62].
Integration of several specialized NLP systems is required for any true and practical
implementation of such a CDS system.
Likewise, compilation of the existing scientific research into central repositories
is a difficult task. Sometimes physicians may be unaware of a promising new treat-
ment just due to the difficulty of parsing the tidal wave of new papers. Scientific
publications have always been widely dispersed across multiple journals and the
modern-day information explosion has only exacerbated the issue. When it comes
to compiling information such as results from genome-wide association studies
(GWAS), the primary method has been a manual curation of the information by
certain individuals within the scientific community: “librarians” so to speak.
Recently, a paper published in Nature Communications used machine learning
systems to automatically compile GWAS information from open-access publications

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DOI: http://dx.doi.org/10.5772/intechopen.92297

Figure 8.
Example of a nursing care plan which represents a formatted health document. Most of these plans were filled
out by hand and many hospitals have transitioned such forms to electronic records. However, older documents
still need to be transferred to digital form. Taken from Wikipedia commons.

and extract GWAS associations into a database with the aim of helping curators.
Though the results are somewhat inconsistent (60–80% recall and 78–94% preci-
sion) it represents one of the many ways NLP is being utilized to aid in medical
discovery [63].

4.1 Examples of natural language processing in healthcare research

There are many exciting possibilities where NLP could be used to improve medi-
cine and medical research. We will discuss a few interesting findings with similar
approaches but different goals. This is by no means an expansive list but highlights
the broad spectrum of possible machine learning applications.
In 2015, a research group published a paper reporting 100% accuracy of predict-
ing onset of psychosis using recorded dialog of clinically high-risk youth. Each
youth was interviewed over a period of 2.5 years every 3 months. Based on the

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Smart Manufacturing - When Artificial Intelligence Meets the Internet of Things

transcripts of these interviews, a machine learning algorithm was trained to predict

whether a patient would develop psychosis. This was done using what is known as
Latent Semantic Analysis to determine coherence of speech using NLP. The sample
size for this study was rather small however (n = 34) [64].
Another study used NLP to identify cirrhosis patients and risk-stratify the
patients. This study was able to correctly identify cirrhosis patients from electronic
health records, ICD-9 code combinations, and radiological scans with a 95.71%
sensitivity and 93.88% specificity [65]. This indicates that such a system could cor-
rectly identify cirrhosis patients based off existing medical data in most hospitals.
Yet another study used NLP to accurately identify reportable cancer cases for
national cancer registries. This method analyzed pathology reports and diagnosis
codes to identify patients with cancer patients using supervised machine learning.
The accuracy was 0.872 with a precision of 0.843 and sensitivity of 0.848 [66]. The
primary goal of this study was to automate the process of reporting cancer patients
to the National Program of Cancer Registries in the United States.
These examples of NLP use in healthcare highlight the wide diversity of applica-
tions within medicine. Language is the primary means of communicating complex
information, doctors’ notes and annotated medical documents hold valuable
insights in populations and individual patient health. The irregularity and variance
of language and extraction of higher-level information into relevant subcategories
makes analysis difficult. Machine learning is showing promising results in perform-
ing such complex analyses.

5. Machine learning in genetics for the prediction and understanding of

complex diseases

Genetic information and technologies have exploded since 2008, creating dif-
ficult challenges in how to handle the exponentially increasing data. Advances in
genetic sequencing speed, namely NGS technologies have exponentially increased
the speed at which a whole human genome is sequenced, while also dramatically
reducing costs. The human genome is a complex physical structure that encodes all
the information of human development and characteristics. The genome is highly
interconnected and deciphering most of these instructions is still a mystery to us.
Variation of genomes between people also increases the complexity of understand-
ing gene interactions.
Many health initiatives have focused on acquiring large sample sizes of human
genomes to help identify statistically relevant trends among different populations
of humans. However, the 23 chromosomes of the human genome contain around
20,000 genes which have been identified as the primary coding sequences for the
proteins necessary in building the biological components of our cells [67]. This
number is still a rough estimate and some estimates indicate that there may be as
many as 25,000 genes or as few as 19,000 [68, 69]. A large swathe of genetic infor-
mation that does not code for any proteins is not included in these estimates.
A growing body of literature indicates that certain sections of what has been
colloquially called genetic dark matter, or missing heritability, exists [70–74]. These
terms refer to the portions of DNA which have no apparent protein coding function,
but may be relevant to the level of gene expression in a person’s genetic code [75, 76].
Levels of gene expression may cause protein overload or deficiency, which can lead
to a variety of health problems. Additionally, structural differences in the physi-
cal structure of how the DNA is bound into chromosomes and then subsequently
unwrapped during both the duplication process and translation and transcription
process, can also affect the level of gene expression.

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For example, methylation or acetylation of the DNA backbone can make it more
difficult (methylation) or easier (acetylation) to unravel the DNA strand during
normal cell processes like replication or protein assembly. Evidence of multiple
copies of the same gene have also been classified in what is described as copy
number variations (CNV) which indicate duplication, triplication, and deletion
events of certain areas of the genome in an individual. Understanding this highly
interconnected and nonlinear relationship between all the different of the areas of
the human genome is difficult.
With machine learning, scientists have begun to find patterns and trends which
can be modeled in a more predictable manner. Utilizing the ever-growing amount
of genetic data, machine learning has the potential of accurately predicting who is
at risk of acquiring certain diseases such as cancers and Alzheimer’s disease. Mental
illnesses such as schizophrenia and bipolar disorder have also been known to run in
families, indicating a possible genetic link.

5.1 Inherited vs. environmental risk

Disease risk can be broadly categorized into inherited risk and environmental
risk. Inherited risk describes a person’s disposition to acquiring complex diseases
due to a trait which is genetically passed down from their predecessors. This
includes genetic mutations contained within their germline DNA which may predis-
pose them to cancers or other health conditions [77, 78].
Environmental risk describes somatic mutations, or mutations to a person’s DNA
due to something they have encountered in their environment. These mutations can
still increase a person’s risk of acquiring a disease but they do not affect the germ-
line, and will not be passed on to their progeny and thus will not be inherited [79].
Inherited risk describes mutations that exist in the human germline and which
will be passed onto the offspring through normal reproduction. Whereas, somatic
mutations may affect organs or a set of cells, germline mutations exist in all the cells
of the offspring. Many of these mutations may be passed through paternal lineage
and there is some indication that certain individuals may have disease predisposi-
tion but which cannot be directly linked to familial history but could still be due to
these hidden germline mutations [80–82].
Several different types of mutations may exist within a human genome. They are
broadly categorized as single nucleotide polymorphisms (SNPs), structural varia-
tions or copy-number variations (CNVs), and epigenetic variations.
SNPs are a single or point mutation of one base pair in the human genome that
occurs in at least 1% of the human population [83, 84]. These mutations are the
most common source of genetic variation and can occur both within coding regions
and outside of coding regions of the genome. SNPs contribute to vast differences
even between relatives and can arise because of both inheritance and development
in the womb. Within SNPs there are common and rare variants, with rare variants
occurring less than 0.5% within the global sample [84].
Structural variations and specifically CNVs are deletions, insertions, duplica-
tions, and inversions of large regions of DNA. These structural differences are
usually inherited and a typical human can have anywhere between 2100 and 2500
structural variations [84]. These variations were found to cover more of the human
genome than SNPs alone [83].
Epigenetic variation describes variations in the chemical tags attached to
DNA or associated structures such as histones, which affects how genes are read
and activated. Epigenetics includes DNA methylation and acetylation, histone
modifications, and non-coding RNAs which all affect the degree to which a gene
may be expressed [85]. As a newer field, it is unclear how much of these epigenetic

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Smart Manufacturing - When Artificial Intelligence Meets the Internet of Things

Type of cancer Cases Controls AUC

Breast invasive carcinoma (men and women) 977 8821 0.81

Glioblastoma multiforme 484 9314 0.86

Ovarian serous cystadenocarcinoma 424 4268 0.89

Thymoma 111 9687 0.78

Uveal melanoma 80 9718 0.80

Table 2.
Sampling of performance of GBM models trained on data from the Cancer Genome Atlas.

variations are inherited from generation to generation, and how much is a result of
environmental factors [86].

5.2 Prediction of cancers through germline copy number variations

One of the exciting methods we have discovered is the utilization of germline

copy number variations in the prediction of different cancers. We have found that it
is possible to use machine learning models, specifically gradient boosting machines
(GBM), a form of decision trees (DT), to predict whether a person has a particular
cancer. The models created were able to predict cancers such as ovarian cancer (OV)
and glioblastoma multiforme with an AUC of 0.89 and 0.86 respectively [87], using
copy number variation data taken from germline blood samples only. This result
indicates that there is a significant inherited portion contributing to cancer risk in
many, if not all cancers. Since these CNVs are also taken from germline DNA, the
likelihood of continued inheritance to future generations is high.
This method does not look solely at SNPs as many previous methods rely on
[88]. Most SNP data specifically looks at mutations within protein coding genes
while ignoring the rest of the genome, whereas our method utilizes a whole genome
approach by averaging the copy numbers of a person’s entire genome as the basis for
predicting cancer. Copy number variation accounts for a large amount of human
genetic diversity and is functionally significant though the exact mechanisms are
still unclear [77, 83].
These results demonstrate that almost all cancers have a component of pre-
dictability in germline CNVs which can be used to predict an individual’s risk to
acquiring that cancer Table 2. Experiments were performed on two independent
databases: The Cancer Genome Atlas and the UK Biobank. The first database
contains about 10,000 individuals and latter contains about 500,000 individuals.
Future studies may improve on the performance and the models could poten-
tially be used as a tool to assess individual risk for diseases. Since the method can
also be easily generalized to other diseases, we anticipate work to continue to
encompass other potentially complex diseases which may have inherited compo-
nents to them.

6. Conclusions

Application of digital technologies such as machine learning in the healthcare

field is entering an exciting era. The collision of informatics, biology, engineering,
chemistry, and computer science will rapidly accelerate our knowledge of both
hereditary and environmental factors contributing to the onset of complex dis-
eases. The potential of utilizing copy number variations in the prediction of cancer

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Applications of Machine Learning in Healthcare
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diagnosis is exciting. Utilizing machine learning to create an interpretable method

of understanding how the genomic landscape interlinks across genes to contribute
to inherited cancer risk could potentially improve patient healthcare on an indi-
vidual level.
Databases such as The Cancer Genome Atlas and UK Biobank are invaluable
resources, providing high statistical power to scientific analysis. As other large-scale
population data projects near completion in the coming decade, the methods laid
on the foundation of The Cancer Genome Atlas and UK Biobank will continue to
benefit and improve as sample sizes easily begin to move into the regime of millions
of patients. Tracking populations around the world will truly aid in the goal of
precision medicine.
Natural language processing will be essential in improving the practicality of
translating scientific findings and results of other machine learning methods into
a clinical setting. Multiple specialized systems will have to be integrated with each
other to effectively extract the wealth of information into a format which can be
utilized effectively by physicians and healthcare professionals.
Image analysis is becoming a staple in many diagnostic endeavors and will
continue to improve the accuracy of radiological diagnosis. Detection of malignant
masses and validation and verification of existing diagnosis has the potential to
improve patient outcomes, while reducing errors. As a non-invasive method of
looking inside the human body, any improvements in healthcare imaging will
reduce the need for risky or ill-informed operations that could lead to other compli-
cations such as infections and blood clots.
The examples discussed in this chapter are some of the most promising works
in applying machine learning in the healthcare field. Resolving big health data into
a usable form will undoubtedly require machine learning techniques to improve.
Infrastructure to support such learning techniques is currently not stable or stan-
dardized. Bringing such methods from concept to practical clinical use is contingent
on both validation of these results and an appropriate infrastructure to support it.
A large variety of devices and storage methods will need to be unified and
standardized to benefit from the increased data collection. Information about how
human genetic variation can contribute to individual susceptibility allows patients
and doctors to make early lifestyle changes in a preventative manner. Likewise, it
can inform physicians of which types of prognostics and diagnostics would be the
most relevant for a specific patient, saving both time and money, while improv-
ing patient outcomes in the long term. Just as AI started with Turing decoding the
enigma machine, we are now going to use AI and machine learning to decode the
secrets of the human body and genome.

Conflict of interest

The corresponding author is a distant relative of the editor of this book.

Notes/thanks/other declarations

The author would like to thank the University of California, Irvine for support
during the writing of this chapter.

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Smart Manufacturing - When Artificial Intelligence Meets the Internet of Things

Author details

Christopher Toh* and James P. Brody

University of California, Irvine, United States of America

*Address all correspondence to: [email protected]

© 2020 The Author(s). Licensee IntechOpen. Distributed under the terms of the Creative
Commons Attribution - NonCommercial 4.0 License (https://creativecommons.org/
licenses/by-nc/4.0/), which permits use, distribution and reproduction for
non-commercial purposes, provided the original is properly cited.

20
Applications of Machine Learning in Healthcare
DOI: http://dx.doi.org/10.5772/intechopen.92297

References

[1] Copeland J. The turing test. Minds Cliffs, NJ. The Knowledge Engineering
and Machines. 2000;10(4):519-539 Review. 1996;11(1): 78-79

[2] French RM. The turing test: The first [12] Alpaydin E. Introduction to Machine
50 years. Trends in Cognitive Sciences. Learning. London: The MIT Press.
2000;4(3):115-122 2014;3:640

[3] Edwards S. World war II at sea: A [13] Kotsiantis SB. Supervised machine
global history. The Journal of American learning: A review of classification
History. 2019;106(1):237 techniques. Informatica (Ljubljana).
2007;31(3):249-268
[4] Turing AM. Computing machinery
and intelligence. Parsing the Turing [14] Hastie T, Tibshirani R, Friedman J.
Test: Philosophical and Methodological The Elements of Statistical Learning -
Issues in the Quest for the Thinking Data Mining, Inference, and
Computer. 2009. p. 23-65 Prediction. Springer Series in Statistics.
Switzerland: Springer. 2009;2(1):93-85
[5] Samuel AL. Some studies in machine
learning. IBM Journal of Research and [15] Ho TK. A data complexity analysis
Development. 1959;3(3):210-229 of comparative advantages of decision
forest constructors. Pattern Analysis &
[6] Samuel AL. Programming computers Applications. 2002;5(2):105-112
to play games. Advances in Computers.
1960;1(C):165-192 [16] Friedman JH. Stochastic gradient
boosting. Computational Statistics and
[7] Fukushima K. Cognitron: A Data Analysis. 2002;38(4):367-378
self-organizing multilayered neural
network. Biological Cybernetics. [17] Friedman JH. Greedy function
1975;20(3-4):121-136 approximation: A gradient boosting
machine. The Annals of Statistics.
[8] Fukushima K. Neocognitron: 2001;29(5):1189-1232
A self-organizing neural network
model for a mechanism of pattern [18] Mason L, Baxter J, Bartlett P,
recognition unaffected by shift in Frean M. Boosting algorithms as
position. Biological Cybernetics. gradient descent in function space. NIPS
1980;36(4):193-202 Conference Proceedings. 1999:512-518

[9] Huang K, Mashl RJ, Wu Y, Ritter DI, [19] Libbrecht MW, Noble WS. Machine
Wang J, Oh C, et al. Pathogenic germline learning applications in genetics and
variants in 10,389 adult cancers. Cell. genomics. Nature Reviews. Genetics.
2018 2015;16(6):321-332

[10] Silver D, Hassabis D. AlphaGo: [20] Längkvist M, Karlsson L,

Mastering the ancient game of go with Loutfi A. A review of unsupervised
machine learning. Google Research feature learning and deep learning
Blog. 2016 for time-series modeling. Pattern
Recognition Letters. 2014;42(1):11-24
[11] Brewka G. Artificial intelligence—a
modern approach by Stuart Russell [21] Lloyd SP. Least squares quantization
and Peter Norvig, Prentice Hall. Series in PCM. IEEE Transactions on
in Artificial Intelligence, Englewood Information Theory. 1982;28(2):129-137

21
Smart Manufacturing - When Artificial Intelligence Meets the Internet of Things

[22] Schmidhuber J. Deep learning in Healthcare Information Management.

neural networks: An overview. Neural 2005;19(2):64-72
Networks. 2015;61(1):85-117
[32] Cottle M, Hoover W,
[23] Hazan E, Klivans A, Yuan Y. Kanwal S, Kohn M, Strome T,
Hyperparameter optimization: Treister NW. Transforming Health
A spectral approach. In: In: 6th Care through Big Data: Strategies for
International Conference on Learning Leveraging Big Data in the Health
Representations, ICLR 2018; Conference Care Industry. Institute for Health
Track Proceedings. 2018 Technology Transformation. New York,
iHT2; 2013
[24] Bardenet R, Brendel M, Kégl B,
Sebag M. Collaborative hyperparameter [33] Wang Y, Kung LA, Byrd TA. Big data
tuning. In: 30th International analytics: Understanding its capabilities
Conference on Machine Learning; and potential benefits for healthcare
ICML. 2013. p. 2013 organizations. Technological Forecasting
and Social Change. 2018;126(1):3-13
[25] Hutter F, Hoos H, Leyton-
Brown K. An efficient approach for [34] Raghupathi W, Raghupathi V. Big
assessing hyperparameter importance. data analytics in healthcare: Promise
In: 31st International Conference on and potential. Health Information
Machine Learning; ICML. 2014. p. 2014 Science and Systems. 2014;2(1):3

[26] Hawkins DM. The problem of [35] The Cancer Genome Atlas
Overfitting. Journal of Chemical Program—National Cancer Institute
Information and Computer Sciences. [Internet]. 2019. Available from:
2004;44(1):1-12 https://www.cancer.gov/about-
nci/organization/ccg/research/
[27] Ng A. Regularization—Solving the structural-genomics/tcga
Problem of Overfitting. Coursera; 2011.
Available from: https://www.coursera. [36] tcga-infographic-enlarge.__
org/learn/machine-learning/lecture/ v100169753.png (1400×2580)
ACpTQ/the-problem-of-overfitting [Internet]. 2019. Available
from: https://www.cancer.gov/
[28] Srivastava N, Hinton G, PublishedContent/Images/images/nci/
Krizhevsky A, Sutskever I, organization/tcga/tcga-infographic-
Salakhutdinov R. Dropout: A simple enlarge.__v100169753.png
way to prevent neural networks from
overfitting. Journal of Machine Learning [37] Peakman TC, Elliott P. The UK
Research. 2014;15(56):1929-1958 biobank sample handling and storage
validation studies. International Journal
[29] Picard RR, Cook RD. Cross- of Epidemiology. 2008;37(2):234-244
validation of regression models. Journal
of the American Statistical Association. [38] Sudlow C, Gallacher J, Allen N,
1984;79(387):575-583 Beral V, Burton P, Danesh J, et al. UK
biobank: An open access resource for
[30] Jothi N, Rashid NA, Husain W. identifying the causes of a wide range of
Data mining in healthcare—A review. complex diseases of middle and old age.
Procedia Computer Science. PLoS Medicine. 2015;12(3)
2015;72(1):306-313
[39] Protocol for the UK Biobank—
[31] Koh HC, Tan G. Data mining Wayback Machine [Internet]. 2019.
applications in healthcare. Journal of Available from: https://web.archive.

22
Applications of Machine Learning in Healthcare
DOI: http://dx.doi.org/10.5772/intechopen.92297

org/web/20060214144838/http://www. for cardiovascular research. European

ukbiobank.ac.uk/docs/draft_protocol.pdf Heart Journal. 2017;44:1158-1166

[40] Elliott P, Peakman TC. The UK [49] Scholtens S, Smidt N, Swertz MA,
biobank sample handling and storage Bakker SJL, Dotinga A, Vonk JM, et al.
protocol for the collection, processing Cohort profile: LifeLines, a three-
and archiving of human blood generation cohort study and biobank.
and urine. International Journal of International Journal of Epidemiology.
Epidemiology. 2008;37(2):234-244 2015;44(4):1172-1180

[41] Gao GF, Parker JS, Reynolds SM, [50] The Health 202: NIH wants 1
Silva TC, Wang LB, Zhou W, et al. million Americans to contribute
Before and after: Comparison of legacy to new pool of gene data. The
and harmonized TCGA genomic Washington Post [Internet]. 2019.
data commons data. Cell Systems. Available from: https://www.
2019;9(1):24-34.e10 washingtonpost.com/news/powerpost/
paloma/the-health-202/2018/01/16/
[42] Bycroft C, Freeman C, the-health-202-nih-wants-1-
Petkova D, Band G, Elliott LT, Sharp K, million-americans-to-contribute-to-
et al. The UK biobank resource with new-pool-of-gene-data/5a5ba45a30fb04
deep phenotyping and genomic data. 69e8840135/
Nature. 2018;562(7726):203-209
[51] FACT SHEET: President Obama’s
[43] Background—EPIC [Internet]. Precision Medicine Initiative.
2019. Available from: http://epic.iarc.fr/ whitehouse.gov [Internet].
about/background.php 2019. Available from: https://
obamawhitehouse.archives.gov/
[44] Leitsalu L, Haller T, Esko T, the-press-office/2015/01/30/fact-
Tammesoo ML, Alavere H, Snieder H, sheet-president-obama-s-precision-
et al. Cohort profile: Estonian biobank medicine-initiative
of the Estonian genome center,
university of Tartu. International [52] Precision Medicine Initiative (PMI)
Journal of Epidemiology. Working Group. The precision medicine
2015;44(4):1137-1147 initiative cohort program—Building
a research foundation for 21st century
[45] Master Decoder: A Profile of Kári medicine. Precision Medicine Initiative
Stefánsson | The Scientist Magazine® Work Group Report to Advisory
[Internet]. 2019. Available from: Committee to Director NIH; 2015
https://www.the-scientist.com/profile/
master-decoder--a-profile-of-kri- [53] FinnGen, a global research project
stefnsson-65517 focusing on genome data of 500,000
Finns, launched. EurekAlert! Science
[46] Gulcher J, Stefansson K. Population News [Internet]. 2019. Available from:
genomics: Laying the groundwork for https://www.eurekalert.org/pub_
genetic disease modeling and targeting. releases/2017-12/uoh-fag121917.php
Clinical Chemistry and Laboratory
Medicine. 1998;36(8):523-527 [54] Le QV. Building high-level features
using large scale unsupervised learning.
[47] China Kadoorie Biobank [Internet]. In: ICASSP, IEEE International
2019. Available from: https://www. Conference on Acoustics, Speech and
ckbiobank.org/site/ Signal Processing—Proceedings. 2013

[48] Littlejohns TJ, Sudlow C, Allen NE, [55] Greenspan H, Van Ginneken B,
Collins R. UK biobank: Opportunities Summers RM. Guest editorial deep

23
Smart Manufacturing - When Artificial Intelligence Meets the Internet of Things

learning in medical imaging: Overview [64] Bedi G, Carrillo F, Cecchi GA,

and future promise of an exciting Slezak DF, Sigman M, Mota NB,
new technique. IEEE Transactions on et al. Automated analysis of free
Medical Imaging. 2016;35(5):1153-1159 speech predicts psychosis onset in
high-risk youths. NPJ Schizophrenia.
[56] Giger ML. Machine learning 2015;1(1):15030
in medical imaging. Journal of the
American College of Radiology. [65] Chang EK, Christine YY, Clarke R,
2018;15(3):512-520 Hackbarth A, Sanders T, Esrailian E,
et al. Defining a patient population
[57] Foster KR, Koprowski R, Skufca JD. with cirrhosis: An automated algorithm
Machine learning, medical diagnosis, with natural language processing.
and biomedical engineering research— Journal of Clinical Gastroenterology.
Commentary. BioMedical Engineering 2016;50(10):889-894
Online. 2014. Online: Published 5 July
2014. Article number: 94 [66] Osborne JD, Wyatt M, Westfall AO,
Willig J, Bethard S, Gordon G. Efficient
[58] Lundervold AS, Lundervold A. An identification of nationally mandated
overview of deep learning in medical reportable cancer cases using natural
imaging focusing on MRI. Zeitschrift fur language processing and machine
Medizinische Physik. 2019;29(2):102-127 learning. Journal of the American
Medical Informatics Association.
[59] Havaei M, Davy A, Warde-Farley D, 2016;23(6):1077-1084
Biard A, Courville A, Bengio Y, et al.
Brain tumor segmentation with deep [67] Collins FS, Lander ES,
neural networks. Medical Image Rogers J, Waterson RH. Finishing
Analysis. 2017;35(1):18-31 the euchromatic sequence of
the human genome. Nature.
[60] Islam J, Zhang Y. Brain MRI analysis 2004;431(7011):931-945
for Alzheimer’s disease diagnosis
using an ensemble system of deep [68] Willyard C. Expanded human gene
convolutional neural networks. Brain tally reignites debate. Nature. 2018;558.
Informatics. 2018;5(2) Online: Published 19 June 2018

[61] Liu M, Zhang J, Adeli E, [69] Ezkurdia I, Juan D, Rodriguez JM,

Shen D. Landmark-based deep multi- Frankish A, Diekhans M, Harrow J, et al.
instance learning for brain disease Multiple evidence strands suggest that
diagnosis. Medical Image Analysis. there may be as few as 19000 human
2018;43(1):157-168 protein-coding genes. Human Molecular
Genetics. 2014;23(22):5866-5878
[62] Demner-Fushman D,
Chapman WW, McDonald CJ. What [70] Galvan A, Ioannidis JPA,
can natural language processing Dragani TA. Beyond genome-
do for clinical decision support? wide association studies: Genetic
Journal of Biomedical Informatics. heterogeneity and individual
2009;42(5):760-772 predisposition to cancer. Trends in
Genetics. 2010;26(3):132-141
[63] Kuleshov V, Ding J, Vo C,
Hancock B, Ratner A, Li Y, et al. A [71] Insel TR. Brain somatic mutations:
machine-compiled database of genome- The dark matter of psychiatric
wide association studies. Nature genetics. Molecular Psychiatry.
Communications. 2019;10(1):3341 2014;19(2):156-158

24
Applications of Machine Learning in Healthcare
DOI: http://dx.doi.org/10.5772/intechopen.92297

[72] Diederichs S, Bartsch L, copy number alteration. Nature

Berkmann JC, Fröse K, Heitmann J, Genetics. 2013;45(10):1134-1140
Hoppe C, et al. The dark matter of the
cancer genome: Aberrations in regulatory [80] Campbell CD, Eichler EE.
elements, untranslated regions, splice Properties and rates of germline
sites, non-coding RNA and synonymous mutations in humans. Trends in
mutations. EMBO Molecular Medicine. Genetics. 2013;29(10):575-584
2016;8(5):442-457
[81] Kuusisto KM, Akinrinade O,
[73] Eichler EE, Flint J, Gibson G,
Vihinen M, Kankuri-Tammilehto M,
Kong A, Leal SM, Moore JH, et al. Laasanen SL, Schleutker J. Copy number
Missing heritability and strategies variation analysis in familial BRCA1/2-
for finding the underlying causes of negative Finnish breast and ovarian
complex disease. Nature Reviews. cancer. PLoS One. 2013;8(8):e71802
Genetics. 2010;11(6):446-450
[82] Zhang J, Walsh MF, Wu G,
Edmonson MN, Gruber TA, Easton J,
[74] Zuk O, Hechter E, Sunyaev SR,
et al. Germline mutations in
Lander ES. The mystery of missing predisposition genes in pediatric cancer.
heritability: Genetic interactions create The New England Journal of Medicine.
phantom heritability. Proceedings 2015;373(24):2336-2346
of the National Academy of Sciences
of the United States of America. [83] Redon R, Ishikawa S, Fitch KR,
2012;109(4):1193-1198. DOI: 10.1073/ Feuk L, Perry GH, Andrews TD, et al.
pnas.1119675109 Global variation in copy number
in the human genome. Nature.
[75] Gibson G, Dworkin I. Uncovering 2006;444(7118):444-454
cryptic genetic variation. Nature
Reviews. Genetics. 2004;5(9):681-690 [84] Auton A, Abecasis GR,
Altshuler DM, Durbin RM, Bentley DR,
[76] Kiser DP, Rivero O, Lesch KP. Chakravarti A, et al. A global reference
Annual research review: The (epi) for human genetic variation. Nature.
genetics of neurodevelopmental 2015;526(7571):68-74
disorders in the era of whole-genome
sequencing—Unveiling the dark matter. [85] Bredfeldt TG, Walker CL.
The Journal of Child Psychology and Epigenetics. In: Comprehensive
Psychiatry and Allied Disciplines. Toxicology. 2nd ed. 2010
2015;56(3):278-295
[86] Heard E, Martienssen RA.
Transgenerational epigenetic
[77] Fanciulli M, Petretto E, Aitman TJ.
inheritance: Myths and mechanisms.
Gene copy number variation and
Cell. 2014;157(1):95-109
common human disease. Clinical
Genetics. 2010;77(3):201-213
[87] Toh C, Brody JP. Chromosomal
scale length variation of germline DNA
[78] Park RW, Kim TM, Kasif S, can predict individual cancer risk.
Park PJ. Identification of rare germline bioRxiv. 2018;10(1101):303339. DOI:
copy number variations over- 10.1101/303339
represented in five human cancer types.
Molecular Cancer. 2015;14(25):1 [88] Lello L, Raben T, Yong SY,
Tellier LC, Hsu SDH. Genomic
[79] Zack TI, Schumacher SE, Carter SL, prediction of complex disease risk.
Cherniack AD, Saksena G, Tabak B, bioRxiv. 2018;10(1101):506600. DOI:
et al. Pan-cancer patterns of somatic 10.1101/506600

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