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Annual Review of Pharmacology and Toxicology

Big Data and Artificial
Intelligence Modeling for
Drug Discovery
Hao Zhu
Department of Chemistry and Center for Computational and Integrative Biology,
Rutgers University, Camden, New Jersey 08102, USA; email: hao.zhu99@[Link]

Annu. Rev. Pharmacol. Toxicol. 2020. 60:573–89 Keywords

First published as a Review in Advance on
artificial intelligence, big data, deep learning, machine learning, rational
September 13, 2019
drug design, computer-aided drug discovery
The Annual Review of Pharmacology and Toxicology is
online at [Link] Abstract
[Link]
Due to the massive data sets available for drug candidates, modern drug dis-
023324
covery has advanced to the big data era. Central to this shift is the develop-
Copyright © 2020 by Annual Reviews.
ment of artificial intelligence approaches to implementing innovative mod-
All rights reserved
eling based on the dynamic, heterogeneous, and large nature of drug data
sets. As a result, recently developed artificial intelligence approaches such as
deep learning and relevant modeling studies provide new solutions to effi-
cacy and safety evaluations of drug candidates based on big data modeling
and analysis. The resulting models provided deep insights into the contin-
uum from chemical structure to in vitro, in vivo, and clinical outcomes. The
relevant novel data mining, curation, and management techniques provided
critical support to recent modeling studies. In summary, the new advance-
ment of artificial intelligence in the big data era has paved the road to future
rational drug development and optimization, which will have a significant
impact on drug discovery procedures and, eventually, public health.

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INTRODUCTION
Drug research and development is a complex, expensive, time-consuming procedure and has a
high attrition rate (1). Drug attritions that happen in clinical studies induce great resource loss, and
currently, nine out of ten drug candidates fail between phase I clinical trials and regulatory approval
(2). Compared to traditional animal models, both in vitro and in silico approaches have great
potential to lower the cost of drug discovery. The application of in vitro and in silico protocols
in the early stages of the drug research and development procedure can reduce the number of
drug attritions by identifying drug candidates with suitable therapeutic activities and excluding
unsuitable compounds with undesirable side effects (3–6). However, the results of in vitro and in
silico testing normally have low correlations to drug activities in vivo, especially for efficacy and
complex side effects (7, 8).
Artificial intelligence (AI), which is sometimes presented as machine intelligence, refers to the
ability of computers to learn from existing data. Computational modeling based on AI is a promis-
ing method to evaluate compounds for their potential biological activities and toxicities. Existing
computational models, such as those based on quantitative structure-activity relationship (QSAR)
approaches (9), can be used to quickly predict large numbers of new compounds for various biolog-
ical end points. The existing models (e.g., those available in commercial drug discovery software)
can make predictions of simple physicochemical properties (e.g., logP and solubility) and thus are
relatively precise in predicting the pharmacokinetic properties of new compounds with simple
mechanisms; however, the models for complex biological properties (e.g., drug efficacy and side
effects) are far from optimal (8, 10) (Figure 1). Critical issues existed in previous QSAR mod-
eling studies such as the use of small training sets (11), experimental data errors in training sets
(12, 13), and a lack of experimental validations (14). The resulting QSAR model predictions of
new compounds were questionable due to their coverage of a limited chemical space (15), existing

Artificial Intelligence

Physical-chemical Membrane Target Cellular Animal Efficacy and

properties transport binding response activities side effects

Data sparsity and variety

Model reliability and predictivity

Figure 1
Challenges of data-driven artificial intelligence modeling in modern, computer-aided drug discovery.

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activity cliffs (16), and overfitting (17, 18). The primary hypothesis of QSAR modeling (i.e., simi-
lar compounds will have similar activities) sometimes proved to be flawed (10, 19–21), indicating
that training sets with only chemical structure information and target activity are not enough to
answer the above challenges.
With the great progress of combinatorial chemistry since the 1990s, large chemical libraries
have become the major source of new chemical development procedures (22, 23). Over the past ten
years, this effort has also stimulated the development of high-throughput screening (HTS) tech-
niques (24–26). HTS is a process that screens thousands to millions of compounds using a rapid
and standardized protocol. Current HTS techniques are usually combined with robotic meth-
ods and require few resources to test a chemical library. Parallel HTS data processing and assay
miniaturization have become increasingly popular in pharmaceutical industries and regulatory
agencies as they greatly reduce the cost of experimental testing (27, 28). The chemical-response
data obtained from HTS keep growing daily and contribute to the current big data environment.
Facilitated by the combined efforts of HTS and combinatorial chemical synthesis, modern screen-
ing programs produce enormous amounts of biological data, especially regarding drug responses
on specific targets (29, 30).
The challenges raised by big data are known as the “four Vs”: volume (scale of data), velocity
(growth of data), variety (diversity of sources), and veracity (uncertainty of data) (31, 32). The data
sets available for drug development, especially in pharmaceutical industries, may involve many
compounds (e.g., from 100,000 to several million) that were tested against many targets (33), and
traditional QSAR modeling and machine learning approaches are not always suited to dealing
with these types of data under these conditions. Furthermore, the uncertainty of available data (or
data sparsity) is one of the major obstacles of using big data (32). Unfortunately, when coupled
with more complex biological mechanisms such as drug responses, the sparsity and variety of
the resulting data increased dramatically from in vitro to in vivo studies (Figure 1). This big
data scenario necessitated the development of new computational approaches to deal with high-
volume, multidimensional, and high-sparsity data sources to predict drug efficacy and side effects
in animals and/or humans.
The challenges to using big data discussed above and the involvement of new types of data (e.g.,
images) have demanded the recent development of novel AI approaches to advance predictive
modeling in modern drug discovery (34–36). The popular AI approaches in the current big data
era are based on deep learning (3, 4, 37). One of the early efforts of applying deep learning in
the drug discovery process in pharmaceutical industries was the 2012 QSAR machine learning
challenge supported by Merck (38). In this challenge, deep learning models showed significantly
better predictivity than traditional machine learning approaches for 15 absorption, distribution,
metabolism, and excretion (ADME) and toxicity data sets for drug candidates developed at Merck.
Since then, and with the development of neural network approaches [e.g., convolutional neural
networks (CNNs)], deep learning has been widely applied to drug discovery approaches. Although
still viewed as a black box algorithm (39, 40), the current progress of AI supported by deep learning
has shown great promise in rational drug discovery in this era of big data. The big data challenges;
relevant AI developments; and modeling for drugs and drug candidates, especially those studies
using deep learning and other new techniques, are the primary focus of this review.

BIG DATA IN DRUG DISCOVERY

The term big data describes a collection of data sets that are so large and complex that they are
too difficult to process with traditional data analysis tools (41). Big data is gaining increasing
recognition in clinical studies and other research areas driven by biological data (42, 43). As one of

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the fields generating a massive amount of data, modern drug discovery has moved into the big data
era. The need for novel computational techniques, including data mining/generation, curation,
storage, and management, brings new challenges and opportunities to the research community.
Several data-sharing projects, in parallel with the developments of HTS techniques in vari-
ous screening centers, were also initiated in the past ten years. For example, PubChem is a public
repository for chemical structures and their biological properties (44–46). In ten years, the number
of PubChem compounds increased from 25 million in 2008 (46) to 96 million in 2018 (47). During
the same period, the number of bioassays that were deposited into PubChem increased from 1,197
in 2008 (46) to over a million in 2018 (47). The current statistics of PubChem indicate that the
repository contains 97.3 million compounds and 1.1 million bioassays ([Link]
[Link]). The tremendous amount of PubChem bioassay data that are updated daily con-
stitutes a publicly accessible big data resource for compounds, including most drugs and drug
candidates, with a variety of target response information. Similar to PubChem, ChEMBL is a
database containing binding, functional, ADME, and toxicity data for numerous compounds (48).
Compared to PubChem, ChEMBL contains a large amount of manually curated data from the
literature. Currently, the ChEMBL database consists of over 2.2 million compounds tested against
over 12,000 targets, resulting in activity data for 15 million compound-target pairs (https://
[Link]/chembl/).
Several other data sources are specifically designed for drugs and drug candidates. For ex-
ample, DrugBank ([Link] is a publicly available database containing all ap-
proved drugs with their mechanisms, interactions, and relevant targets (49). The latest release of
DrugBank (version 5.1.2, released December 20, 2018) contains 12,110 drug entries, including
2,553 approved small-molecule drugs, 1,280 approved biotech (protein/peptide) drugs, 130 nu-
traceuticals, and over 5,842 experimental drugs. DrugMatrix ([Link]
drugmatrix/[Link]), on the other hand, focuses on the toxicogenomic data of drugs to re-
duce the time to formulate a xenobiotic’s potential for toxicity. The current DrugMatrix database
contains large-scale gene expression data from tissues of rats administered over 600 drugs, mostly
targeting several major organs (e.g., liver). The Binding Database (BindingDB) is a public, web-
accessible resource of drug-target binding data, shown as measured binding affinities (50). The
targets included in BindingDB are proteins/enzymes that are considered drug targets. BindingDB
currently contains 1,587,753 binding data for 7,235 protein targets and 710,301 small molecules
([Link]
The public big data sources can also be characterized by the size of electronic files for these data
sets. For example, the current PubChem bioassay database has around 240 million bioactivities,
which are contained in 30 GB of XML files. Instead of using personal computers with central
processing units, the use of new hardware techniques such as cloud computation (41, 51) and
graphics processing units (GPUs) (52) is necessary to process and analyze these available big data.

BIG DATA MODELING CHALLENGES: MISSING DATA

AND BIASED DATA
The response profiles of 2,118 approved drugs tested against 531 PubChem assays (each assay
having at least 25 active responses among these drug molecules) are shown in Figure 2. The results
were generated using an in-house automatic data profiling tool ([Link] (53).
There are more than a million data points in this response profile. Nevertheless, many responses
in this profile were shown as missing data (Figure 2). Furthermore, the ratio of active versus
inactive responses is also biased (approximately 1:6 in this profile). For example, two well-known
drugs were included in this profile: acetaminophen (CAS 103-90-2), which has 16 active and 213

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Active results PubChem assays

Inconclusives/
untested results
Inactive results
Drugs

Figure 2
Bioprofile of 2,118 approved drugs from DrugBank (x axis) represented by the response data obtained from 531 PubChem assays
(y axis). Each assay against all drug molecules (one column) has at least 25 active responses (red spots). Data from DrugBank (https://
[Link]) and PubChem ([Link]

inactive responses, and acetylsalicylic acid (aspirin, CAS 50-78-2), which has 14 active and 237
inactive responses. Due to the nature of the HTS techniques, the HTS data normally consist of
much fewer active than inactive responses (21, 54), especially for the drugs. In an early review of
pharmacological space based on 4.8 million unique compounds, only 275,000 of them showed one
(or more) active response when tested against 1,036 targets (55), indicating that most of the testing
results were negative. Notably, the drugs that showed the most active responses in public big data
sets are for chemotherapy purposes, which normally have critical side effects and other off-target
interactions. For example, bortezomib (CAS 179324-69-7) is a chemotherapy drug used to treat
multiple myeloma and mantle cell lymphoma. It has the most active responses (258 actives and 49
inactives) in the response profile of Figure 2.

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The missing data issue is a common problem of big data modeling (56). In previous stud-
ies, a common solution was to develop QSAR models for individual assays and use the resulting
models to predict target compounds that were not tested against these assays (19, 20, 57). This
approach was applicable only when the predicted data used for model development had simple
biological mechanisms (e.g., logPs or structural rigid target bindings). However, this process still
introduced uncertainty into the modeling process due to the prediction errors from QSAR mod-
els (57). When dealing with heterogeneous and complex data (e.g., clinical data), advanced sta-
tistical methods such as multiple imputations are needed (58, 59). To reflect the biased nature
of HTS data, emphasis should be given to active rather than inactive results during modeling
procedures (53). Early-stage computational studies normally used pharmacophore modeling to
identify chemical features that were responsible for relevant bioactivities (60–62). The later mod-
eling projects using machine learning approaches needed the biased training sets to be prepro-
cessed by using various methods such as downsampling to balance active and inactive results (63–
65).

ADVANCING ARTIFICIAL INTELLIGENCE FROM MACHINE

LEARNING TO DEEP LEARNING
The historical progress of AI coupled with the increase of the data size used for model develop-
ment and hardware improvement in drug discovery is summarized in Figure 3. The concept of AI
was born in the 1950s (66) and was used in drug discovery after the first study of QSAR was pre-
sented in the 1960s (67). In the early stage of drug discovery (e.g., before the 1990s), the common
computational approaches used for model developments were linear regressions (68). In these
early studies, the chemical descriptors used for modeling were also limited to chemical structural
features, such as atomic type and fragmental descriptors (69, 70). The advancement of AI in drug
discovery was first facilitated by the development of novel chemical descriptors such as topological
descriptors (71) and molecular fingerprints (72, 73), which greatly increased the size/categories of

Data sizes Processors

Deep
Terabytes neural networks Multi-GPA cloud
computing

Gigabytes
Deep learning
GPU
Validations and
applicability domains
Megabytes
64-bit CPU
Artificial neural networks
Big data

Computer-aided
Kilobytes drug discovery
Birth QSAR 32-bit CPU
of AI Variable selections

Bytes 8-bit CPU

Docking

1950s 1960s 1970s 1980s 1990s 2000s 2010s

Figure 3
The historical progress of artificial intelligence in drug discovery coupled with increasing data size and
computer power (shown as processor improvement).

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descriptors calculated from training sets. Instead of using all available descriptors, descriptor selec-
tion was integrated into the modeling procedure, e.g., the genetic algorithm (74, 75) and simulated
annealing (76). Instead of using linear regression, new machine learning approaches, which were
developed based on nonlinear modeling algorithms such as k-nearest neighbors (77), support vec-
tor machines (78), and random forest (79, 80), were used frequently in modeling studies from the
1990s to the 2000s. In the same period, model validation was emphasized and treated as a must-
have component of modeling (81). Instead of only showing self-correlations, the developed models
using these new machine learning approaches were always validated using cross-validations, ex-
ternal validations, and/or experimental validations (14, 63, 82, 83). In addition, the applicability
domain became standard practice for model development (17, 84–86). In the early 2000s, QSAR
modeling, together with relevant studies (e.g., docking), became a well-developed workflow based
on the progress of AI discussed above (Figure 3). These milestones of AI in drug discovery are
emphasized in other reviews (9, 87–91).
In addition to the development of AI, the computational power of hardware and the available
data for modeling were also significantly improved to facilitate this progress (Figure 3). The
early-stage computational modeling of small training sets by simple algorithms (e.g., linear
regressions) did not require significant computational power. The advancement of computa-
tional power and the availability of biological data for drugs enabled the application of novel
modeling techniques such as large-scale networks to address challenges in drug discovery. The
first application of the neural network, which was designed as a computational tool in the 1980s
(92), in drug discovery was reported in 1989 (93). Since then, various neural network approaches
have been applied to drug discovery (90, 94). The first popular approach was the artificial neural
network (ANN) (95, 96), which focuses on the variable selection procedure (97). This approach is
a machine learning algorithm inspired by biological neural networks such as those in the human
brain. With several variables as the input (e.g., chemical descriptors), ANN approaches form
hundreds of artificial neurons, which are connected with relationships (quantified as weights) in
the form of a network. A single neuron might have some effectiveness in predicting output, but the
actual predictions are made by the network consisting of hundreds or even thousands of neurons.
Since they learn from the input data, ANNs represent an excellent machine learning approach for
constructing nonlinear relationships among the variables and the target biological activities (98).
The advanced computational models using various machine learning approaches, such as ANNs,
required powerful computers and benefited directly from the hardware developments in the 1990s
(Figure 3).
The concept of deep learning was originally presented together with ANNs in the 1980s (4).
However, neural networks did not show significant advantages over other machine learning ap-
proaches when data used for model development are limited (99, 100). From the 1990s to 2000s,
computer hardware was still not adequate for training neural networks with many hidden layers
and/or when the data sets for model development were large. In the 2010s, hardware develop-
ment reached the milestone of using GPUs and cloud computing, which directly benefited neural
network modeling studies (Figure 3). Advanced as one of the major interests of AI by various in-
formation technology companies, deep neural networks (DNNs), sometimes referred to as deep
neural nets, with many hidden layers were developed to address challenging questions such as
speech recognition (101). In the Google DeepMind project of 2015, an AI program based on a
DNN with 13 hidden layers first mastered the game of Go, which has long been viewed as the
most challenging of the classic games for AI (102). The milestone paper of deep learning was
published at almost the same time (103), and the big data concept was proposed the next year (41,
104). Deep learning was immediately applied to the life sciences and demonstrated its capability to
identify complex patterns in biological systems (4, 105). The first project in which deep learning

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approaches showed significantly better performance than other machine learning approaches for
drug discovery was a QSAR machine learning challenge supported by Merck (38). Another simi-
lar effort organized by the National Center for Advancing Translational Sciences of the National
Institutes of Health (NIH) was to model around 12,000 chemicals, including many drugs, for 12
different toxic effects (106). In this competition, DeepTox, a computational toxicity model based
on DNNs outperformed other models based on machine learning approaches (107).
Besides the modeling challenges mentioned above, there have been various individual deep
learning studies for drug discovery in the past three years. For example, Wen et al. (108) reported
a deep learning model developed to predict interactions between drugs and their biological tar-
gets based on 15,524 drug-target pairs obtained from the DrugBank database. Another similar
deep learning study was performed using transcriptome data obtained from the Library of Inte-
grated Network-Based Cellular Signatures program (109). Furthermore, multitask learning based
on DNNs is a modeling approach that allows multiple related tasks to be modeled simultaneously.
Modeling several biologically related end points (i.e., bioactivities sharing similar mechanisms) for
drug discovery purposes through multitask learning has shown superior performance to traditional
QSAR models by reducing overfitting, solving issues of biased data, and identifying variables from
related tasks (110–113). The high performance of these DNN models demonstrates the advan-
tages of using deep learning approaches to model large data sets and select meaningful features.
However, there were also recent reports that showed mixed results from the comparison between
deep learning and machine learning modeling (114, 115). Since deep learning is a brand-new con-
cept being applied to computer-aided drug discovery, there are no universal criteria for selecting
relevant modeling parameters and/or constructing the modeling workflow (115).

OTHER AREAS OF COMPUTATIONAL MODELING UTILIZING

ARTIFICIAL INTELLIGENCE FOR DRUG DISCOVERY
Rational Nanomaterials Design
Modern nanotechnology highly impacts drug discovery by offering biocompatible nanomaterials
(e.g., nanomedicines with desirable therapeutic activities and low side effects) to the drug research
and development process, especially as versatile yet reliable carriers for the delivery of drugs to
treat systemic diseases such as cancers (116, 117). Early efforts of using AI in nanomodeling for
drug discovery were based on molecular dynamic (MD) simulations. For example, several studies
using MD simulations detected the insertion of nanoparticles in the plasma membranes of the re-
cipient cells and an overall change in the cell membrane structure (118). Later, the same approach
was used to estimate the affinity of carbon nanotubes to organic molecules (119). In another study,
a set of nanoparticles was tested in vitro in four cell lines, and the potential membrane perturbation
effects of these nanoparticles were studied (120). The reaction behaviors of individual nanoparti-
cles were also investigated under certain conditions using MD simulations (e.g., interactions with
or passing through membranes), along with the effects of the size, density, position, distribution,
length, and type of surface ligands on the biological properties of the nanomaterials (121). The ad-
vantage of MD simulations is that they can precisely simulate molecular structures, but the clear
disadvantages are that modeling procedures are computationally expensive and cannot provide
rapid predictions for big databases due to the current limitations of computational resources. An-
other computational approach is to apply traditional QSAR modeling methods to nanomaterials.
For example, the QSAR technique was used to create predictive models for nanoparticles with
similar or different metal cores (122). Recently, membrane-nanoparticle interactions were mod-
eled based on the atomization energy of the metal oxide, the period of the nanoparticle metal, and
the primary size of the nanoparticle (123).

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H2O molecules

Accessible
ligand layer

Surface Inaccessible ligand layer

ligands

Core

Figure 4
Nanomaterial surface simulations for computational modeling: surface ligand orientations and accessibility
assessments.

The current application of AI approaches in nanomodeling has been limited to designing new
nanomaterials due to a lack of suitable chemical descriptors. Although descriptors calculated from
only the surface ligands are useful in predicting specific bioactivities/properties of nanomateri-
als, as described above, the effects of the nanomaterial’s size/shape, density, position, distribution,
length, and type of surface ligands were not considered in these studies. Some other nanomodel-
ing studies have incorporated descriptors derived from experimental properties (e.g., nanoparticle
size) (123, 124) or even biological data (e.g., proteomics data) (125, 126). Due to the diversity and
complexity of nanomaterial structures, Puzyn et al. (127) argued that no universal nano-QSAR
model can accurately predict the biological properties of variable nanomaterials. Figure 4 presents
a recent methodology for nanostructure simulations in the modeling procedure (128). Briefly, the
properties and bioactivities of nanomaterials were largely determined by their surface chemistry.
To simulate the nano surface chemistry correctly, the surface ligand orientations and accessibility
of functional groups needed to be considered in the calculations (Figure 4). For example, in an
early modeling of nanohydrophobicity, the contributions of heavy atoms and functional groups
to nanologP values were correlated with their accessibility by solvent molecules (128). In a re-
cent study, an advanced method of integrating the solvent-accessible surface into calculations can
be viewed as a universal nanologP calculator (129). A similar modeling strategy has been applied
to model nanocellular uptake capacities (130) and several other nano bioactivities. The result-
ing models were utilized to design and synthesize several new nanoparticles with desired nano
bioactivities (130).

Convolutional Neural Networks and Image Modeling

The CNN is a special network modeling approach inspired by neuroscience to imitate images
within the visual cortex, where individual neurons respond to stimuli only in the receptive fields.
Different neurons can partially overlap with each other to cover the entire receptive field. The
CNN architecture is constructed in a way that hidden layers are particularly adept at screening
multidimensional input such as the red, green, and blue saturation values obtained from thousands
of pixels for an image. In the training process, the CNN approach uses kernels and grids of a

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predefined dimension to scan the image and learn to recognize certain critical features such as
lines and contours for a human face. The concept of CNNs was proposed in the 1980s for image
recognition purposes but did not draw great attention until the 2010s (4). This approach has
become well known, as it has dominated all image recognition challenges since 2012, and it is now
the base of image/speech recognition, video analysis, language understanding, and other relevant
applications (131).
As one of the most popular deep learning approaches, CNNs have been used for image model-
ing in clinical diagnoses such as cancer (132), Alzheimer’s disease (133), and heart disease (134). In
traditional drug discovery, CNNs were also applied to analyze image data obtained from experi-
mental drug testing, such as HTS results (135). Due to its unique advantages in image recognition,
CNNs were also used to recognize 3-D experimental and virtual images to predict ligand-protein
interactions (136, 137). In some studies, CNNs were coupled with other computational approaches
to realize specific goals. For example, CNNs were used as a new approach to recognize molecu-
lar features from drug molecular graphs (138). In this study, drug molecules were treated as 2-D
graphs with atom features. The CNN was used to transform the input molecular graphs into new
molecular features for training purposes. In another study, an advanced CNN approach called the
survival convolutional neural network was used to predict the cancer outcomes of patients based on
histological images and genomic biomarker data (139). Furthermore, CNNs were able to function
as a text-mining technique to extract drug-drug interaction data from biomedical literature (140).

Personalized Medicine
A drug commonly interacts with multiple targets, including both on- and off-targets, and drug effi-
cacy and side effects are greatly affected by this (141). The perturbation of an individual biological
system (e.g., a patient) by a drug molecule is determined by various genetic, epigenetic, and en-
vironmental factors. To identify this hidden hierarchical information, personalized medicine was
designed to respond to the individual characteristics of each patient (142). Personalized medicine
strongly relies on a scientific understanding of how an individual patient’s unique characteristics,
such as molecular and genetic profiles, make this patient vulnerable to a disease and sensitive
to a therapeutic treatment. Driven by biomarker studies starting in the late 1990s, hundreds of
genes have been identified for their contributions to human illness, and genetic variability in pa-
tients has been used to distinguish individual responses to dozens of treatments (142). Along with
the huge amount of data generated by these studies, such as the Human Genome Project (143),
computational modeling has become one of the most important tools for personalized medicine.
Drug-target predictions (144), metabolic network modeling (145), and population genetics pat-
tern identifications (146) are several recent advancements in this field that rely on computational
modeling. Under the NIH Precision Medicine Initiative (147), many data generation and sharing
initiatives and computational modeling efforts have arisen to support the expansion of precision
medicine. For example, the Genomic Data Commons program of the National Cancer Institute
aims to provide a data repository that enables data sharing across cancer genomic studies in support
of precision medicine (148). So far, 33,549 case studies have been submitted and shared via this
portal ([Link] Although it is not the focus of this review, genome sequencing
analysis has been a widely applied approach involving AI techniques, and there are many reviews
available on this popular bioinformatics topic (149–151).

CONCLUSIONS
AI is a promising method to greatly reduce the cost and time of drug discovery by providing eval-
uations of drug molecules in the early stages of development. In the current big data era, clinical

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and pharmaceutical data continue to grow at a rapid pace, and novel AI techniques to deal with
big data sets are in high demand. The recent deep learning modeling studies have shown advan-
tages compared to traditional machine learning approaches for this challenge. However, standard
criteria and modeling workflows are still needed for deep learning models to be applicable. The
applications of AI have been widely extended into all relevant areas beyond traditional drug dis-
covery. Coupled with database curation, web portal development as data repository servers, and
the improvement of computer hardware, AI and recent deep learning studies have paved the road
to modern drug discovery.

DISCLOSURE STATEMENT
The author is not aware of any affiliations, memberships, funding, or financial holdings that might
be perceived as affecting the objectivity of this review.

ACKNOWLEDGMENTS
The author thanks Dr. Wenyi Wang, Daniel P. Russo, and Heather Ciallella for their contributions
to figure and text editing.

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