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Published in final edited form as:

Cell. 2020 April 02; 181(1): 92–101. doi:10.1016/j.cell.2020.03.022.

How Machine Learning will Transform Biomedicine

Jeremy Goecks, Vahid Jalili, Laura M. Heiser, Joe W. Gray
Department of Biomedical Engineering, Oregon Health & Science University

Abstract
This Perspective explores the application of machine learning toward improved diagnosis and
treatment. We outline a vision for how machine learning can transform three broad areas of
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biomedicine: clinical diagnostics, precision treatments, and health monitoring, where the goal is to
maintain health through a range of diseases and the normal aging process. For each area, early
instances of successful machine learning applications are discussed, as well as opportunities and
challenges for machine learning. When these challenges are met, machine learning promises a
future of rigorous, outcomes-based medicine with detection, diagnosis and treatment strategies
that are continuously adapted to individual and environmental differences.

eToC blurb - Gray

Gray and colleagues provide an ambitious visión of how machine learning could impact
healthcare, outlining the progress and challenges of applying machine learning approaches to
clinical diagnostics, precision therapeutics, and health monitoring.
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Introduction
Machine learning leverages sophisticated algorithms operating on large-scale, heterogeneous
data sets to uncover useful patterns that would be difficult or impossible for even well-
trained individuals to identify. There already are many applications of this approach
throughout science and society ranging from game playing (Silver et al., 2018) to product
recommendations (Batmaz et al., 2019) to controlling self-driving cars (Bojarski et al.,
2016). In biomedicine, work in the human genome project (Venter et al., 2001), efforts in
cancer omics (e.g., The Cancer Genome Atlas (Tomczak et al., 2015), the International
Cancer Genome Consortium (Zhang et al., 2019), and the Clinical Proteomic Tumor
Analysis Consortium (Ellis et al., 2013)), and numerous international machine learning
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competitions such as DREAM challenges (Saez-Rodriguez et al., 2016; Sage Bionetworks,

2020) and the Critical Assessment of Genome Interpretation (Andreoletti et al., 2019) have
shown the power of this approach. The ability to collect and analyze large datasets related to
medical treatments and outcomes promises to transform medicine into a data-driven,
outcomes-oriented discipline with profound implications for disease detection, diagnosis and
treatment. Collection of molecular and phenotypic data has become pervasive, and includes

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genomic testing for personalized treatment of cancer, high-resolution two-and three-

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dimensional anatomical imaging of organs, histological analyses of tissue biopsies, and

smart watches that monitor heart rates and notify wearers of irregularities (Shilo et al.,
2020). These and many other collected data provide the raw material for a future of early,
more accurate diagnoses, personalized treatments, and ongoing monitoring in support of
overall health.

Machine learning will help realize a future of improved health care by unlocking the
potential of large biomedical and patient datasets. Early uses of machine learning in
diagnosis and treatment have shown promise to diagnosis breast cancer from x-rays
(McKinney et al., 2020; Wu et al., 2019), discover new antibiotics (Stokes et al., 2020),
predict onset of gestational diabetes from electronic health records (Artzi et al., 2020), and
identify clusters of patients that share a molecular signature of treatment response (Zitnik et
al., 2019). Automated pattern recognition through machine learning is essential due to the
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enormity and complexity of biomedical data; manual analysis is both inefficient and
untenable. Equally important, many human diseases involve a complex constellation of
changes that occur dynamically and vary from patient to patient. Understanding this
complexity requires analysis of large-scale heterogeneous data to identify novel patterns
that, after rigorous evaluation, can be used for diagnosis and treatment. Machine learning,
then, can assist biomedicai scientists and medical professionals by identifying and
summarizing meaningful patterns from large datasets (Rajkomar et al., 2019). Careful
evaluation of the patterns found and predictions made by machine learning applications in
diagnosis and treatment is essential. “Ground truth” data, in which associations between data
and outcome are known, can be used to rigorously evaluate the performance of novel
algorithms. Such evaluation data may be quantitative, such as biomarker reduction on
treatment, or more qualitative such as overall patient health. It is also important to appreciate
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that ground truth may change depending on individual characteristics such as age, gender,
and environmental exposures.

Recognizing this, there are a growing number of research programs designed to collect and
organize large scale datasets linking variables to health status, which can be used to train and
evaluate machine learning approaches. Programs in cancer that aggregate molecular profiles
from experimental model systems or patient samples together with diagnostic, prognostic,
and therapeutic responses provide examples of these valuable data repositories. For example,
the Cancer Dependency Map (Tsherniak et al., 2017) has collected multimodal molecular
profiles, drug response, and genetic viability data on more than 1,000 cancer cell lines. The
AACR Project GENIE (AACR Project GENIE Consortium, 2017) has collected genomic
profiles and clinical data for more than 19,000 patients, and the ASCO CancerLinQ is
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building a similar database of hundreds of thousands of patients. Coupled with advanced

algorithms, such programs have the potential to transform our understanding of diseases and
improve our ability to predict disease outcomes.

Machine learning is a subdiscipline of artificial intelligence, and the main conceptual

approaches in machine learning are summarized in Table 1. Whereas artificial intelligence
includes all methods for enabling computers to display human-like understanding and
intelligence, machine learning is focused specifically on developing algorithms to learn from

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data. General classes of machine learning methods include: (a) supervised learning in which
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data groups are associated with a specific outcome; categorical data (e.g., disease vs.
normal) rely on classification methods whereas continuous values (e.g., strength of response
to therapy) are used in regression methods, (b) unsupervised or semi-supervised methods to
cluster data into discrete groups that can then be manually labeled and associated with
outcome, (c) ensemble learning, where results from multiple computational models are
combined to produce a final prediction, can lead to more accurate predictions by enabling
models to generalize to new data better (d) deep learning, which uses artificial neural
networks, a formalization modeled on the human brain, to recognize patterns or associations
in the data, is especially useful when working with unstructured data such as images, speech,
and text and (e) Bayesian learning, in which prior knowledge is encoded into the learning
process, is especially useful in data-poor situations.

There are two complementary approaches that can be used with any of these learning
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methods and are especially useful for biomedical applications. Many biomedical datasets
have a large number of features (dimensions), and the number of features may exceed the
number of data points. Dimensionality reduction can help improve the performance of
machine learning approaches by selecting a subset of relevant attributes of a dataset or
combining attributes into a smaller number that capture variability in a dataset. Reducing the
dimensions of a dataset is also useful for visualizing data or model predictions. When data
are distributed across multiple sites and cannot be moved to create a single dataset for
machine learning, federated learning approaches are used to learn incrementally across all
the data (Konecny et al., 2016; Yang et al., 2019). Federated learning is especially important
in many biomedical applications where data contain sensitive or protected health
information that cannot be easily shared. Most of these approaches are conceptually mature
but are now finding increased use as structured biomedical data become available and as
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computer technology becomes sufficiently powerful to enable discovery of subtle but

important patterns in large data sets. A recent review provides a brief tutorial on machine
learning approaches in the life sciences (Camacho et al., 2018). The application goals and
available data dictate appropriate machine learning methods to use. Table 2 lists prototypic
examples of machine learning applications for medical diagnosis and treatment.

We expect that applications of machine learning will have a profound impact on many
aspects of health management as computers optimized for machine learning increase in
power and as infrastructure for accurate data collection and curation becomes more widely
deployed. Immediate biomedical opportunities summarized in the following sections include
earlier and more accurate disease detection, better diagnosis, and more durable and tolerable
treatments. Of course, the accuracy of the underlying “learned” relationships depends on the
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accuracy and magnitude of the data on which learning is based. This can be enhanced
substantially by widely deploying standardized electronic medical record systems designed
specifically to support machine learning and by supporting their widespread use. Acquisition
of data “at home” using smartphones, commercial home assistant devices (e.g. Amazon
Echo, Google Home), and other electronic devices will further enhance robust biomedical
machine learning. Looking ahead, we envision these trends merging to enable outcomes-
based personalized management of patient health (Figure 1) using algorithms that increase
in accuracy as the quantity and quality of data grows.

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In this Perspective, we outline a vision for how machine learning can be applied to make
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critical advances in biomedicine. We focus on three biomedical areas: improved clinical

diagnostics, precision treatment, and health management and monitoring. For each area, we
describe opportunities for machine learning applications to enable new insights or improve
on current state-of-the-art approaches, discuss successful early applications of machine
learning, and highlight unmet needs to be addressed. We conclude by identifying several
cross-cutting challenges that, if solved, will help realize the full potential of machine
learning in biomedicine.

Improved Diagnostics from Clinical Imaging and Molecular Tests

Technological advances in clinical testing are generating orders of magnitude more data than
tests in the past. High-fidelity imaging tests now produce large two-, three or four-
dimensional (the fourth dimension being time) images of tissue and organs, and molecular
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tests can provide assessment of hundreds or even thousands of genes and proteins. Machine
learning is both essential and ubiquitous for automated analysis of diagnostic features in
these data that are strongly associated with disease type, status or response to treatment.

The use of deep learning to extract meaning from biomedical images is one of the most
active areas of current research. Several recent publications have shown that computer-aided
detection (CAD) software using machine learning can interpret radiologie images on par
with medical professionals indicating the power of this approach. For example, deep
learning-based CAD software was able to detect diabetic retinopathy at high levels of
accuracy (Gulshan et al., 2016) and to retrospectively identify invasive and in-situ breast
cancer of all grades similar to radiologists (McKinney et al., 2020; Wu et al., 2019). A recent
review found that deep learning based approaches performed as well as medical
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professionals across a range of medical imaging diagnostic tasks, though many of these
studies are small and have yet to perform a prospective evaluation (Liu et al., 2019).
Importantly, deep learning approaches benefit from large data sets and will increase
continually in accuracy as the sizes of the training data sets grow.

Molecular assays can identify genetic mutations and quantify gene expression levels and
protein abundance from a variety of samples, including blood, saliva, and tissue. Machine
learning has the potential to increase the utility of these data by discovering complex sets of
biomarkers associated with various disease states, which ultimately can inform patient
outcome and identify effective treatment strategies. Some examples from cancer biology
include using DNA methylation (Kang et al., 2017) and nucleosome positioning (Heitzer et
al., 2019) from blood to predict tumor tissue of origin, quantifying cellular pathway
activation levels in biopsies and other tissue samples (Way and Greene, 2019; Way et al.,
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2018), predicting genomic features of brain cancers using magnetic resonance images
(Chang et al., 2018a), and forecasting cancer patient outcomes based on multi-omics
(Chaudhary et al., 2018) or imaging-omics integrations (Mobadersany et al., 2018). Beyond
cancer, machine learning has been used to identify individuals with sleep deprivation
through analysis of mRNA in the blood, informing how sleep insufficiencies negatively
affect health (Laing et al., 2018). Through integration of multiple data types and biomarkers,

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machine learning models are likely to be substantially more accurate than current practice,
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which is often limited to a few markers and reflects only a narrow view of complex diseases.

Joint human-computer diagnostic approaches such as those illustrated in Figure 1, are likely
to become common because they take advantage of the strengths of both humans and
computers. In this collaborative approach, physicians will make a final diagnosis by
integrating all available information, including that provided by machine learning systems
(Ahuja, 2019). Machine learning systems will have a key role by automating routine
diagnosis, flagging challenging cases that require more human input, and providing
additional information useful in making diagnoses (e.g., (Ardila et al., 2019)). Moreover,
machine learning systems may use different features than medical professionals to make
diagnoses, though care will be required to assess the biological utility of such features. As a
result, approaches that integrate knowledge from both medical professionals and advanced
algorithms will lead to improved diagnoses. Ensuring that machine learning software is
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transparent will be critical before widespread deployment and adoption. ‘Transparency’ in

this context includes description of the optimized objectives, strengths, quantitative
performance and limitations of a particular algorithm (Cai et al., 2019) as well as the
procedures used to validate the algorithm. These attributes will help medical professionals
decide when and how to use machine learning applications to obtain valid results and
improve decision making. Applications that use machine learning can help build trust in the
system and facilitate deeper understanding of the underlying biological mechanism of
disease by explaining predictions, such as by highlighting the most important features used
(Ching et al., 2018; Litjens et al., 2016).

As more advanced clinical testing technologies are coupled with machine learning, it will be
important to consider tradeoffs between disease detection rates, patient outcomes, and other
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factors that impact patient health and quality of life. Disease detection rates may increase
with the use of machine learning technologies, and disease-specific research will be needed
to differentiate indolent versus fatal disease to avoid over-treatment and to identify disease
subtypes in order to guide the selection of the most effective treatments for each subtype.
Careful framing of clinical goals that can be connected to evaluation and validation metrics
will ensure that machine learning improves patient care and overall health (Chen et al.,
2019b).

Precision Treatment through Multiscale Modeling and Expert Guidance

One of the most promising application areas for machine learning is precision medicine,
where a patient receives medical care and treatment tailored to their personal disease profile.
Precision oncology, where the goal is to prescribe cancer treatments based on tumor
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molecular characteristics, is a prime example of the challenges and opportunities for

machine learning in precision medicine. In current practice, individual molecular markers
such as somatic mutations and gene expression levels are often used to inform treatment
selection. However, responses are often highly variable between patients due to differences
at other genomic and epigenomic loci as well as anatomic disease distribution (Brown et al.,
2019; Kobayashi and Mitsudomi, 2016; Rotow and Bivona, 2017). Further complicating

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precision oncology is that there are hundreds of potential drugs and not every combination
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can be tested for every disease profile (Gerstung et al., 2017; Kurnit et al., 2018).

One way that machine learning can help overcome these challenges is through the
development of multifactorial predictive models that are robust against individual diversity.
For example, single-purpose models have been built to forecast the functional consequences
of biological changes, such as how genetic mutations influence splicing and gene expression
(Xiong et al., 2015) as well as transcription factor binding (Chen et al., 2019a). Machine
learning models have also been built to predict drug response in cancer cell lines (Chang et
al., 2018b), transfer predictions from cell lines to patient tumors (Chiu et al., 2019a), and
forecast patient response to therapies based on clinical response data (Huang et al., 2018).
Future advancements in modeling for precision therapeutics are likely to operate over
multiple scales and serve multiple purposes. Multiscale modeling will use large biological
datasets to investigate the growth and development of an organism across diverse temporal
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and spatial domains. Already there are computational models of human-virus interactions
(Lasso et al., 2019), cell-cell interplay such tumor-immune cell interactions, and even whole
cells (Metzcar et al., 2019; Rahman et al., 2017; Sakamoto et al., 2018). Eventually we
anticipate that computational models of organs and entire individuals—so-called “digital
twins” (Bjornsson et al., 2019)—will be developed. The goal of digital twins will be
multifaceted, such as predicting the efficacy of different combination therapies that have
never been used together and modeling the impact of disease on different organs.

While multiscale models may become accurate enough that their predictions can be used
directly for treatment, we envision an intermediate stage in which machine learning
approaches generate a ranked list of suggested therapies that can be used by expertly trained
physicians to help guide treatment decisions. For instance, patient-derived laboratory models
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could be used to test predictions from computational models, with the best-performing
predictions recommended for use in treatment. This hybrid approach has many advantages:
machine learning models can dramatically reduce the space of potential treatment
combinations to be considered and identify others that might otherwise be overlooked. An
experimental validation step could be added to provide additional evidence that a predicted
therapy is likely to be effective.

Precision medicine will also be advanced by using machine learning to automatically mine
and search expert knowledge in published literature and patient databases (Rajkomar et al.,
2019). Patient databases, usually in the form of electronic health records (EHRs), represent a
rich source of information about diagnosis, treatment, and treatment response for large
patient cohorts. Early efforts have attempted to use natural language processing algorithms
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to mine publications (Dong et al., 2018), EHRs (Shickel et al., 2018), and clinical reports
(Kreimeyer et al., 2017; Pons et al., 2016) for useful knowledge, such as biomarker-therapy
associations and biological pathways of interest. Other applications have used structured
information from EHRs to predict disease onset (Artzi et al., 2020). Machine learning will
help harness this information and make it useful for precision medicine through advanced
approaches that address the unstructured nature of data and metadata in publications and
EHRs. Of course, the EHR mining approach assumes that the information needed to

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establish a useful association is accurately and completely captured. Unfortunately, this is

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not always the case and future work will be needed to increase the utility of EHR analyses.

Health Management and Monitoring

We envision a shift in how complex diseases are treated, moving from the goal of a cure to
one of disease management. This comprehensive health management approach will strive to
maintain health through a range of diseases and the normal aging process. Health
management is demanding as it requires ongoing monitoring of all aspects of health for
potential disease, choosing treatments suited to individual patients, and adapting treatments
based on patient response (Figure 2). Here machine learning has a key role to play, largely
by integrating many of the ideas already discussed for diagnosis and treatment into a
continuous learning approach.
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Outside of clinical settings, wearable devices and at-home smart electronic devices provide a
new avenue for health management. These devices can collect large amounts of fine-grained
data on patient health status that can be used by machine learning applications to suggest
one-time actions, changes in daily activities, or referral to a physician for assessment and
testing. Wearable devices now include sensors for motion, pulse, respiratory rate, body
temperature, blood pressure, oxygen levels, and other biometrics. Prototype applications
show how data from wearables might be useful, including: diabetes management (Chang et
al., 2016), detection of atrial fibrillation (Bumgarner et al., 2018), blood cholesterol
monitoring (Fu and Guo, 2018), early detection of Parkinson’s disease (Lonini et al., 2018),
self-adherence to medications (Car et al., 2017; Toh et al., 2016), and early warning of heart
attack (Sahoo et al., 2017). Speech-driven home assistants have been used to detect agonal
breathing, an audible biomarker that is an early sign of cardiac arrest (Chan et al., 2019). In
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the future, machine learning software is likely to be used to identify new biomarkers from
wearable and audio sensor data, perhaps by integrating data across different types of devices.
Both traditional supervised learning and deep learning are likely to play roles in developing
models from wearable data.

Using machine learning together with data collected from smartphones provides new
opportunities for diagnostics as well. Deep learning approaches have been applied to analyze
pictures from smartphone cameras to identify different types of skin cancers (Esteva et al.,
2017) and also to diagnose diabetic retinopathy (Micheletti et al., 2016). Recent studies have
found that sensory data (e.g., voice, tapping, response time, and accelerometer data)
collected from smartphones and processed using machine learning can be used to monitor
symptoms and progression of Parkinson’s disease (Arora et al., 2015; Espay et al., 2016;
Ginis et al., 2016; Pereira et al., 2016). These prototype applications suggest a role for
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machine learning where wearables, home devices, and smartphones are used to capture all
kinds of data, including biometric measurements, photos, dietary intake, and even
environmental information (i.e., the “exposome” (Vermeulen et al., 2020)). By connecting
this information with diagnoses, machine learning will be used to identify patterns within
the data that suggest a particular diagnosis.

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The foundation of health management is the ongoing monitoring of individual behavior and
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body functioning through home and wearable devices together with readouts from routine
blood sampling. Personalized models of baseline functions and activity will be built by
customizing population-level models with data collected for each individual. A key
advantage of this approach is that personal baselines can be established and deviations from
baselines--which may indicate a change in health status--can be detected. Using
personalized models, machine learning applications will monitor individuals for any changes
from normal and notify individuals when a change requires consult with a medical
professional. An interesting possibility along these lines is suggested by recent work
showing that monitoring of individual internet symptom searches (in essence, self-reported
health issues such as weight loss, bronchitis, cough, chest pain, etc.) coupled with machine-
learned tendencies from many individuals can enable early detection of lung (White and
Horvitz, 2017) and pancreatic (Paparrizos et al., 2016) cancers. This could lead to a
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physician or patient alert system that recommends medical attention when a more serious
issue may explain the seemingly innocuous symptoms searched for. Of course, many issues
regarding privacy would have to be overcome to make this possible.

Once in a clinical setting, high-fidelity imaging and molecular testing will be interpreted by
medical professionals with the help of machine learning to identify noteworthy biomarkers
and make a final diagnosis. Disease diagnoses that require treatment will use multiscale
modeling and automated search results for similar patients to inform treatment selection.

After diagnosis and treatment, health management begins again with ongoing monitoring of
individual health. This time, however, there are multiple goals that a machine learning
system must meet: monitor how the individual is responding to treatment, watch for any
adverse effects, and monitor overall health and changes from baseline not accounted for by
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treatment. Machine learning will help adapt the initial personalized model to include the new
diagnosis and therapy information, creating an expected trajectory on treatment that will
serve as the new baseline.

Health management across a person’s lifespan will require data integration and modeling at
a level of sophistication and automation that is only possible with machine learning. Each
step in health management—building personalized models and using them to monitor for
and accurately detect anomalies, aiding physicians in diagnosis and treatment through
automated processing of large datasets and patient databases, and updating individual
models for new diagnoses and treatments—is data intensive and requires automated pattern
recognition of complex datasets. Health management will also continuously learn as models
will be updated with availability of new data. Two general approaches for continuous
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learning are to build new predictive models or to update existing models, and more work is
needed to understand the strengths and limitations of these approaches for different
applications.

Challenges and Concluding Thoughts

For machine learning to play a transformative role in diagnosis and treatment, it is necessary
to develop high-quality, well-curated datasets. High-quality datasets have several important

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benefits: they improve the predictive power of machine learning methods while reducing the
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size of the data needed for training and the complexity of the learned representations.
Famously, machine learning approaches for image recognition accelerated when ImageNet
(Deng et al., 2009), a corpus of labelled and ontologically-linked images, was introduced.
Similar efforts in biomedicine are needed across the variety the tasks where machine
learning may be applied.

Creating high-quality datasets for machine learning applications in diagnosis and treatment
will require addressing technical, legal, and economic issues that often result in siloed
biomedical data that are not standardized. As discussed above, federated learning provides a
technical solution for combining data amongst siloed systems because no actual data
movement is necessary and individual privacy can be protected. Wearables and home
devices provide a way to collect accurate data, and machine learning can be used as a
preprocessing step to extract accurate analytic and clinical data from unstructured sources
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such as electronic health records and publications. Legal procedures must be developed for
the secure management and analysis of Private Health Information (PHI) and community
and legal standards that define the performance of these procedures must be established.
Biomedical institutions and individuals must be incentivized to engage in data
standardization and sharing. Similarly, insurers, the pharmaceutical industry, and agencies
that support biomedical research must be willing to invest the infrastructure, data
acquisition, and data curation required to generate high quality data.

Approaches and incentives for data sharing that promote diversity in the datasets used for
learning are needed as well. This includes national and international data sharing standards
that make it possible to obtain data from both major medical centers and community clinics.
It is likely, for instance, that machine learning applications that improve patient treatment
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response in major medical centers may not perform well in community settings due to
differences in overall care and patient populations. However, the ultimate goal of biomedical
data collection for machine learning is to obtain suitable representative data from patient
cohorts to develop accurate machine learning models that will generalize to diverse
populations. Therefore there must be a concerted effort to also account for variables such as
patient status prior to treatment, treatment regimes, age, gender, race, ethnicity, and
environmental exposures.

Rigorous evaluation approaches are needed for biomedical machine learning applications,
especially in settings where continuous learning is required. In our view, the performance of
a machine learning system is best measured by the accuracy of its predictions in a
prospective setting. We advocate for an iterative approach to machine learning that includes:
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training with retrospective data, algorithm lock-down and deployment, followed by

assessment of the application’s accuracy based on predictions obtained during deployment.
Data collected during deployment, coupled with additional or larger retrospective datasets,
can then be used to retrain and optimize the algorithm, followed by a subsequent
deployment-evaluation cycle. Evaluating continuous learning systems--such as those we
envision for health monitoring that must adapt to changes in health status or habits--will
likely require tightening this loop and use of data collected during the deployment phase to
detect limitations or failures. Quantifying not only accuracy but also confidence intervals is

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critical, as some uses of machine learning will be more tolerant to inexact predictions than
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others and confidence intervals can be used by physicians to inform decision making.
Iteratively training and deploying machine learning applications poses regulatory challenges
as most diagnostic and therapeutic tests assume that models and data are fixed. When
models are updated in response to new data or adapted for new diagnoses or treatments,
ongoing evaluation is needed to ensure that predictions remain accurate. Real or simulated
datasets that are multi-modal, expansive, and longitudinal will be needed to ensure robust
evaluation of biomedical machine learning applications.

While the challenges outlined above are significant, we are optimistic that they can be
overcome. Further, we believe the effort is worthwhile, as success promises a future of
rigorous, outcomes-based medicine with detection, diagnosis, and treatment strategies that
are continuously adapted via machine learning to individual and environmental differences
and enable comprehensive health management.
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Acknowledgements
J.G. and J.W.G. are supported by National Cancer Institute grant U2C CA233280. J.G. is supported by National
Cancer Institute grant U24 CA231877. L.M.H. and J.W.G. are supported by the National Institutes of Health grant
U54 HG008100 and National Cancer Institute grant U54 CA209988. J.G., L.M.H., and J.W.G. are supported by the
Prospect Creek Foundation. J.W.G. is supported by the Susan G. Komen Foundation. L.M.H. is supported by the
Breast Cancer Research Foundation and The Jayne Koskinas Ted Giovanis Foundation.

Declaration of Interests

J.W.G. receives research support from Micron and ThermoFisher and has stock in NVIDIA, Microsoft, Amazon
and Google (Alphabet) and GE.

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Figure 1.
How machine learning applications could help individuals maintain health. At home,
machine learning may help in early detection of disease, monitoring response to treatment,
and adherence to treatment regimens. In the clinic or hospital, machine learning may aid
medical professionals to diagnosis and tune treatment for an individual patient. The dashed
line shows how a patient moves between home and clinical settings and how machine
learning can help at each step to maintain health.
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Figure 2.
Combining data collected from both home (left) and clinical settings (right), or combining
predictive models built at home and in the clinic, has the potential to lead to comprehensive
and integrated models that support personalized health management. Comprehensive models
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are more likely to perform well as they incorporate more information about an individual,
and these models have the potential to be applied in the home, clinic, or wherever an
individual may be.
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Table 1.

Key concepts in machine learning.

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Concepts Definition
Supervised, Supervised learning predicts labels or classes on future data based on past data that includes labels/classes.
unsupervised, and semi- Unsupervised learning identifies structure, usually clusters, amongst unlabeled data. Semi-supervised learning first
supervised learning performs unsupervised learning, and humans label structures found from unsupervised learning.

Classification and Both are supervised learning methods. Classification predicts discreet categories such as normal vs. diseased while
regression regression predicts real-valued outputs such as response to therapy.

Ensemble learning Ensemble methods build many models and use the average of all models to produce predictions. Common
ensemble approaches include random forests, gradient-boosting, and stacking/meta-ensembles.

Deep learning Multi-layer artificial neural networks that can learn complex non-linear functions. Very useful for unstructured data
such as images, speech, or text but typically do not provide insights in to the aspects of the data that are driving the
functions.

Bayesian learning Methods that combine prior knowledge in addition to data to perform machine learning.

Dimensionality Reduces the number of attributes or features of a dataset by selecting important features or combining features to
reduction capture variance in a dataset. Often used to improve performance of machine learning models and to aid
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visualization.

Federated learning Approaches for incrementally learning from data distributed in multiple locations and which cannot be combined
into a single dataset. Federated learning is useful when data are located in multiple clinical systems or when
learning from sensitive personal data.
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Table 2.

Example applications of machine learning for diagnosis and treatment.

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Dataset Goals Successes Data type ML method

Patient molecular 1. Discover Cancer subtyping (Curtis et al., • High-dimensional, Unsupervised clustering for
patient profiles subtypes or stratify 2012; Gao et al., 2019) structured data cluster discovery; supervised
without clinical data patients • Unlabeled data learning and deep learning
2. Identify for subtype assignment.
similarities among
clustered patients

Patient or laboratory Predict most Cancer cell line drug response • High-dimensional, Supervised learning, deep
molecular profiles efficacious prediction (Chiu et al., 2019b; structured data learning, and ensemble
with clinical data therapies Costello et al., 2014) • Unlabeled data learning

Images and Automated Medical imaging diagnostics • Unstructured data Deep learning
associated diagnoses diagnoses (Liu et al., 2019) • Labeled data

EMR data + clinical Predict clinical Diagnosis of gestational • Structured and Traditional machine learning
outcomes outcomes diabetes (Artzi et al., 2020); unstructured data on structured data with
patient similarity (Lee et al., • Labeled data labels. Deep learning/natural
2018) language processing to mine
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unstructured data. Federated

learning.

Wearable and home Early diagnoses Detection of atrial fibrillation • Unstructured, Both supervised and deep
device ambient data (Bumgarner et al., 2018) and longitudinal data learning approaches, with
collection agonal breathing, an audible • Labeled data adjustments made for time-
biomarker of cardiac arrest series analyses.
(Chan et al., 2019)

Deep longitudinal Ongoing health None yet due to lack of • Structured and Continuous learning
data management available datasets unstructured data
• Labeled data
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Cell. Author manuscript; available in PMC 2021 April 02.