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Generate bioinformatics data using Generative Adversarial Network: A Review

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 Generate bioinformatics data using Generative
Adversarial Network: A Review
Sharmilan S 1, Hapugahage Thilak Chaminda 2
Informatics Institute of Technology, Affiliated to Robert Gordon University, Scotland
Colombo, Sri Lanka
sharmilan_s@outlook.com 1, hapugahage@gmail.com 2
Abstract – Data is the most important part in machine learning.
In bioinformatics field the sensitivity of the data is high and
due to that the accessibility of the data for a secondary purpose
(e.g.: research) is consist with many legal and ethical issues.
Due to that in many bioinformatics researches collecting the
data consume more time than the development phase. There
are some researches done to solve the legal and ethical issues
by anonymising the data using encryption, de-identification
and perturbation of potentially identifiable attributes. For
some extend those solutions restricted the data breach but in
other hand anonymized data not performed well during the
analysis and mining tasks. Recently Generative adversarial
networks (GANs) have become a research focus of artificial
intelligence. The goal of GANs is to estimate the potential
distribution of real data samples and generate new samples
from that distribution. Here, researcher review GAN in
bioinformatics to generate data sets, presenting examples of
current research. To provide a useful and comprehensive
perspective, Researcher categorize research both by the
bioinformatics data and GAN architecture and flow.
Additionally, discussed about the issues of GAN in
bioinformatics to generate data sets and suggest future
research directions. Researcher believes that this review will
provide valuable insights for researchers to apply GAN to
generate bioinformatics data sets.
I INTRODUCTION
Access to data is one of the bottlenecks in the development
of machine learning solutions to domain-specific problems.
The availability of standard datasets (with associated tasks)
has helped to advance the capabilities of learning systems in
multiple tasks. However in bioinformatics and medical field
it is hard to collect the standard datasets in a huge amount
[33]. For example in medical, defense, security and some
other fields the sensitivity of the data is high. In that case the
access to data is highly controlled.
The exponential growth of the amount of biological data
available raises two problems: on one hand, efficient
information storage and management and, on the other hand,
the extraction of useful information from these data. The
second problem is which requires the development of tools
and methods capable of transforming all these
heterogeneous data into biological knowledge about the
underlying mechanism [19]. Medical data will be divided in
to two main types such as text and image. Many researchers
done to predict or analysis the medical issues or dieses using
the images [19] [33]. And same time many researchers done
to predict the things using patient records or electronic
health records [8] [36] [33]. In that case the sensitivity and
privacy of the data comes in to play. As most of the health
records consists with personal details.
If we take a process of prediction models it all depend on the
data sets. The attribute selection will be done based on
looking at the data set. The collected data will be
preprocessed and use for model training and testing. So the
model learns about the things that provided based on those
data sets. If the gathers data is poor in quality wise or if the
data is class imbalanced then the trained model will be
inefficient [27]. So to improve this whole process collected
data should be balanced and quality one. Also it should
cover a wide range of inputs.
Modern machine learning methods based on deep neural
network architectures require large amounts of training data
to achieve the best possible results [25]. But due to the
privacy and legal issues it’s not possible to access large scale
of real patient data. But if try to get access some sort of data
sets then the quality and the distribution of the data will be
poor in many times [8] [33] [19] [36]. So in this paper
researcher going to discuss about the issues and difficulties
in the bioinformatics researches in terms of access and
availability of data. Also discussing about the recent
researches done using GAN to generate various things
including data sets as well. Also how GAN improving the
field of bioinformatics in terms of generating data samples.
II BIOINFORMATICS
Bioinformatics is an interdisciplinary field that develops
software tools and machine learning models to understand
the biological data. As it’s an interdisciplinary area of
science, it combines computer, science, mathematics to
analyses and understand biological data. As it’s a wide and
complicated area bioinformatics have different genres
inside itself. Most popular ones are sequence analysis, Gene
and protein expression, Analysis of cellular organization,
Structural bioinformatics and Network and systems biology
[26]. Even we can divide these things in to sub parts as well.
For an example DNA sequencing, Sequence assembly,
Genome annotation, Computational evolutionary biology,
Analysis of mutations in cancer are the sub parts of
sequence analysis [26]. The National Center for
Biotechnology Information reports that there are three main
scientific applications of bioinformatics. They categorize
them as Evolutionary Biology, Protein Modeling and
Genome Mapping [29]. As it’s improving dramatically,
over the past decades the quantity and quality of biological
information has skyrocketed.
As bioinformatics containing mathematics and computer
programing, the advancement of machine learning models
and artificial intelligence largely improved the
bioinformatics field as well. Deep learning has advanced
rapidly since the early 2000s and now demonstrates state-
of-the-art performance in various fields as well as
bioinformatics also [20]. Even the invention of GAN helped
the bioinformatics researchers to develop biomedical data
and images to solve some complicated areas of
bioinformatics [33] [11] [33] [19] [41]. Using the machine
learning and data mining models bioinformatics solved
many complicated issues like predicting diseases in early
stage, calculate the patient risk level in early stage and even
modeling and remodeling the RNA and DNA [26] [28].
There are applications and tools developed by researchers
to detect or identify various types of cancer, brain tumor,
diabetes, heart attack and etc. [26] [29]. So as a conclusion
the field of bioinformatics absorbed the advancement of
computing and AI and used effectively in biology and
medical
III BIOINFORMATICS DATA
A wide array of biomedical data are generated and made
available to healthcare experts and researchers for the
purposes of research. However, due to the diverse nature of
the medical data, it is difficult to analyze and predict
outcomes [28]. When we consider diseases most of the
symptoms and causes are differ from region to region or
even country to country. Also for many disease, symptoms
and causes are vary from many non-medical parameters
such as climate, behaviors and culture [33] [29] [43]. So if
a data collected from a specific place and used for research
will not applicable for another place with different non-
medical parameters. When a researcher tries to access the
medical data many of the important parameters will be hided
due to the privacy issues of patients such as date of birth,
birth place, addictions and some diseases like HIV [30] [17].
Most of the times collected data will not cover all the classes
of prediction or even there will be no data for some rare
cases. With this type of data used to train a supervised model
to predict or classify, it will not able to predict rare cases or
even it will predict them wrong. So the efficiency and the
accuracy of the model will go down due to the class
imbalanced.
A Quality and quantity of the data
Generally a successful decision support or prediction
system needs a good amount of quality data. The data can
be collected as domain knowledge or real patient data sets.
But the first approach is more expensive and we need to
collect good quality and quantity of knowledge [33] [32].
But the other one is easy to get but the amount of data that
needed is the issue. During the big data boom as similar as
other industries health care industry also understand the
importance of the data and they started to collect and stored
them for the future works. Even there are researches done to
unify all the medical data in to a one central system to solve
the data diverse issues as well [35]. But if a researcher try to
access the data they will face many legal and ethical issues
as these data are sensitive as its collected form patients.
Basically to train a supervised model the amount of required
data is not a constant. The amount of data required is depend
on the complexity of the problem and the models as well
[25] [10] [32]. Most of the bioinformatics researches are is
more complex and sensitive. Due to that researchers needs
to build an efficient models to provide high accuracy
predictions. Also if the model build using some nonlinear
algorithm then they need more data samples for training and
testing compare to linear model algorithms [25].
B Lack of data in terms of quality and quantity
Data mining and machine learning is typically associated
with solving real world problems that are characterized by a
large amount of data. However, in practice, collecting large
amounts of data in medical field is infeasible. Although data
mining could make important advances in this field, several
challenges must be addressed [11]. Existing works that
apply data mining to small datasets have shown the
following challenges:
• The over fitting problem. Obviously, a
classification decision based on a small number of
instances is susceptible to the over fitting problem,
because of lack of samples representative of the
whole data distribution [27].
• Due to the small amount of data, it will cause very
poor classification performance [13].
• Noise. The noisy data instances will lead to
unclear class boundaries and reduce overall classification
accuracy.
New researches and innovations are needed in data mining
technology to address these challenges [11]. Class
imbalance is another major problem with data and
especially in medical field. In the imbalance data set the
class having more number of instances is called as major
class while the one having relatively less number of
instances are called as minor class [27] [10]. Most machine
learning algorithms works best when the number of
instances of each classes are roughly equal. When the
number of instances of one class far exceeds the other,
problems arise. In such situation most of the classifier are
biased towards the major classes and hence show very poor
classification rates on minor classes. It is also possible that
classifier predicts everything as major class and ignores the
minor class as it not have enough evidence for the minor
class [27].
IV LEGAL AND ETHICAL ISSUES
One reasons behind limited access stems from the fact that
EHR data are composed of personal identifiers, which in
combination with potentially sensitive medical information,
induces privacy concerns. As a result, access to such data
for secondary purposes (e.g., research) is regulated, as well
as controlled by the health care organizations that are at risk
if data are misused or breached [17]. The review process by
legal departments and institutional review boards can take
months, with no guarantee of access [11]. This process
limits timely opportunities to use data and may slow
advances in biomedical knowledge and patient care. Health
care organizations often aim to mitigate privacy risks
through the practice of de-identification [22], typically
through the perturbation of potentially identifiable attributes
(e.g., dates of birth) via generalization, suppression or
randomization. And then they made the data available for
research uses [21]. But for most of the bioinformatics
researches in diseases predication or risk analysis field
needs a wide range of data that includes exact date of birth
and residential details. So if the data is randomized then
there will be a chance that the accuracy and efficiency is not
up to the high level.
V OTHER ISSUES WHILE ACCESSING DATA
As considering patient data still in many countries like Sri
Lanka there is no EHR management in large scale [40]. And
for some diseases and medical cases such as maternal,
autism and many mental diseases still there is no recorded
data sets and only having the domain knowledge
[36][15][38]. So if there is a bioinformatics research need to
be done to build some machine learning models using data
then the researches by them self they need to collect and
record the data. So the time allocated for research will be
diverted to collect the data and store them [36] [40]. Most
of the times researchers are not in the medical fields, due to
that their domain knowledge is limited in those areas
compare to the doctors and specialist in medical field. So
they may miss some important attributes while building a
model as they will only consider about the data and the
attribute variant. As a conclusion many developed countries
having issues of privacy and storing patient data and the
same time some developing countries still figuring out ways
to collect and store the data. So for these type of countries
there will be no history of previous data and they will only
have current data cases.
VI DATA BREACH AND HACKING
Now a day’s health care industry facing the big issue was
data breaching. As they storing sensitive patient data
including their personal details. Totally 40 biggest health
care record breaches done all around the world in 2017 until
October [14]. Also the data breaches done in places where
the data shared for secondary purposes like researches. To
avoid the privacy issues while if there is a data breach,
health care industries used information randomizes and
generalization techniques. However, this approach is not
impregnable to attacks, such as linkage via residual
information to re-identify the individuals to whom the data
corresponds [24]. Also anonymising and sharing patient
data is the new trend in health care industry. But still this
process consume more time to anonymising the data [24].
Researchers not able to predict the outcome or symptoms by
region or a particular place because the residential data are
anonymised.
In recent times researches done to generate data samples to
overcome these issues. In Recent years advancement of auto
generated data went to next extend to create total fake
records based on some real record samples. This type of
solutions will resolve the data access issues as well as the
data piracy and security issues.
VII GENERATIVE ADVESARILA NETWORKS
GANs are neural networks that learn to create synthetic data
similar to some known input data. For instance, researchers
have generated convincing images from photographs of
everything from bedrooms to album covers, and they
display a remarkable ability to reflect higher-order semantic
logic [2] [1] [37] [19] [11] [7]. GAN was invented by ian
goodfellow [16]. It was first introduced in 2014 and
afterword’s there are many number of GAN variants were
introduced by researchers for different tasks [23]. The
concept is basic as if anyone want to improve some skills
especially in games they will compete with an opponent
better than them. Then they will analyze what went wrong
or which point it went wrong. Afterword’s they use that
knowledge to improve their skills. Same as that hear in GAN
generator network will always compete with the high
accuracy discriminator and then learn his mistakes and
improve his accuracy. So in one point generator will beat
the discriminator [16]. The efficiency and accuracy of the
generator depend on how powerful the discriminator is, so
all the time in GAN must to have a powerful discriminator
[23] [4].
A Architecture and Flow
The architecture of the GAN consist with two classifier
models. One is discriminator and other one is generator. The
task of generator model to learn and generate things such as
images, sound, and etc. and other one is discriminator.
Discriminator will classify the generated things as real or
fake by its trained knowledge. Discriminator model
determines whether a given image looks like a real image
from the dataset or like an artificially created image. This is
basically a binary classifier that will take the form of a
normal convolutional neural network over the course of
many training iterations, the weights and biases in the
discriminator and the generator are trained through back
propagation. The discriminator learns to tell "real"
things/data apart from "fake" things/data created by the
generator. And once the generated one classified as fake
then generator will get that feedback from discriminator and
stat generate a new sample. Until the discriminator fooled
by the generator to classify generated samples as real one.
The sample structure of GAN diagram given below.
Fig. 1 Generative Adversarial Network Architecture
In this section researcher going to discuss about the training
and learning process of GAN. To get in to the training
process first, researcher describe the optimization of
discriminator D given generator G. Similar to the training of
sigmoid function based classifiers, training the
discriminator involves minimizing the cross entropy [23].
The loss function given in the below formula.
1 the D as it is and train the G to minimize the discrimination
𝑂𝑏𝑗𝐷 (𝜃𝐷 , 𝜃𝐺 ) = − 𝐸𝑥~𝑃𝑑𝑎𝑡𝑎(𝑥) [𝑙𝑜𝑔𝐷(𝑥)]
2
1 model achieve the global optimal solution if and only if
− 𝐸𝑧~𝑃𝑧 (𝑧) [𝑙𝑜𝑔(1 − 𝐷(𝑔(𝑧)))]
2 pdata = pg [23] [16]. That time discriminator fooled by the
(1)
In GAN the training data will be in 2 parts. One is the real
data pdata(x) and another one is the generated data
distribution pg(x). Where x is sampled from real data
distribution pdata(x), z is sampled from the prior
distribution pz(z) such as uniform or Gaussian distribution,
and E(·) represents the expectation [23]. Its slightly
differentiate from the conventional binary classification. In
generator need to minimize equation 1 value to get a best
solutions. In continuous space, equation 1 can be
reformulated as below.
(2)
The above equation will achieves its minimum value at y =
m/ (m + n). Hence, given generator G, the objective
equation (2) achieves its minimum value based on the below
equation.
𝑃𝑑𝑎𝑡𝑎 (𝑥)
𝐷𝐺∗ (𝑥) =
𝑃𝑑𝑎𝑡𝑎 (𝑥) + 𝑝𝑔(𝑥)
(3)
This is th ebest solution of discriminator D. based on the
equation 4, discriminator of GAN estimates the ratio of two
probability densities. D(x) denoting the probability of X.
that meand D(x) denoting the real data, so the discriminator
try to make the D(x) as 1. And same time if the input data
comes from G (z). G(z) denoting the generated data, then
the discriminator try to make that D(G(z)) as 0 [16]. And he
same time generator G tries to make it approach 1. Since it’s
a min max game between G nad D, the loss function of G is
ObjG(θG) = −ObjD(θD, θG). Therefore, the optimization of
GAN can be formulated as a minimax problem:
𝑚𝑖𝑛 𝑚𝑎𝑥 𝑉(𝐷, 𝐺) = 𝐸𝑥~𝑃𝑑𝑎𝑡𝑎(𝑥) [𝑙𝑜𝑔𝐷(𝑥)] + 𝐸𝑧~𝑃𝑧 (𝑧) [𝑙𝑜𝑔(1
𝐺 𝐷
− 𝐷(𝑔(𝑧)))]
(4)
As a conclusion, during the learning process of GAN, needs
to train the discriminator D to maximum accuracy to
discriminating input data. That means discriminator should
have high accuracy to confirm whether the input data is real
or generated one. Then need to train the the generator G to
minimize log(1 − D(G(z))) [23] [16]. Normally in GAN first
train the discriminator D to its maximum accuracy and not
train the G. then once the training completed for D then fix
accuracy of D. as this process continue in one point the
generator and, discriminator classify the generated data as
the real data.
VIII RELEATED WORKS TO GENERATE DATA SETS USING
GAN
There is a research done to generate electronic health
records for secondary purposes [11]. The access and
availability of the electronic health records has motivated
the bioinformatics advances in research side. However still
the EHR systems not automatically provide easy access to
the data for researches. The main reason behind the limited
access is the data consist with personal details. So the health
care organizations put high security over their data because
it can easily misused or breach.
As a solution they used GAN and created a new approach
call medGAN (medical Generative Adversarial Network)
[11]. medGAN will generate realistic synthetic patient
records. It’s trained by using real records to create fake
records. They used auto encoder and GAN to generate high
dimensional discrete variables from binary to count values
[11]. Also they proposed mini batch averaging to effectively
avoid mode collapse. That will improve the efficiency of
learning with batch normalizations [11].
They used GAN along with the auto encoder to generate the
datasets. The model was trained using real world data sets
and from that they try to produce similar generated sets. So
the generate network will create data samples and the
discriminator will tell whether the created one is real or fake.
If the data is fake then the generator will recreate another
sample by using the advice from discriminator. For the
experiment they used 3 large electronic health record sets.
They used a proprietary dataset from a private health
organization, which consists of 10-years of longitudinal
medical records of 258K patients, MIMIC-III dataset
(Johnson et al., 2016; Goldberger et al., 2000), which is a
publicly available dataset consisting of the medical records
of 46K intensive care unit (ICU) patients over 11 years old
and a proprietary dataset for a heart failure study from a
private health organization, which consists of 18-months
observation period of 30K patients [11].
They carried variety of experiments and evaluation to check
the quality and the performance of the system. They found
that min batch averaging increased the performance of
medGAN [11].
Fig. 2 Score distribution for real and fake datasets [11].
Also the Independent sampling naturally shows great
performance. medGAN, seems to capture the dimension-
wise distribution relatively well, showing specific weakness
at processing codes with low probability. To evaluate the
medGAN they used two EHR datasets. Then they evaluated
the generated data by get reviews from medical experts. To
get the reviews from doctors they randomly got 50 records
from real data and another 50 from generated data and
shuffle them and presented to experts to scale from 1-10
based on the realistic of the data. The results are given in
figure 2 [11].
The findings suggested that medGAN’s synthetic data are
generally indistinguishable to a human doctor except for
several outliers. The fake records identified by the doctor
are mainly lacked appropriate medication codes [11]. And
these can happen in real world scenarios as well when the
data is missing or not recorded.
medGAN uses GAN to generate real-world multi-label
discrete electronic health records (EHR). Through rigorous
evaluation using real datasets, medGAN showed impressive
results [11]. According to medical filed there is no efficient
way for researchers to access the real data. Considering that
medGAN will improve the healthcare industry and provide
good amount of contribution to bioinformatics field in terms
of data sets. For future directions, they plan to explore the
sequential version of medGAN, and also try to include other
modalities such as lab measures, patient demographics, and
free-text medical notes [11].
Now a days in bioinformatics images are widely using for
predictions and analysis. But the availability of annotated
data in large amount becoming increasingly critical [33].
However, annotated medical data often scarce and costly to
obtain. In recent advances of deep learning and deep
networks are required large amount of data to be trained. A
wide availability of such data may allow researchers to
develop and validate more sophisticated computational
techniques. As a solution for this problem researchers
introduced GAN model to generate synthesis retinal color
images [33]. It’s an image simulation based approach. So
using that researchers can create synthetics retinal images as
much as they want.
Researchers proposed to implement an adversarial auto
encoder for the task of retinal vessel network synthesis. Also
researchers used generated vessel trees as an intermediate
stage for the generation of color retinal images, which is
accomplished with a GAN. To train the model they used
Messidor-1 dataset that consist automatic retinal vessel
segmentations data [33].
This model achieved a 0.9755 AUC on the DRIVE test set,
a result aligned with state-of-the art methods for retinal
vessel segmentation. Only images from Messidor-1 with
grades 0, 1 and 2 were used in this work, reducing the
number of example pairs to 946. This dataset was randomly
divided into training (614 pairs), validation (155 pairs) and
test (177 pairs) sets, which were downscaled to 256 × 256
before training the model [33]. This data preprocessing
happened to avoid the poor generalization of their vessel
segmentation technique, which produced incorrect
segmentations for images in a later stage of diabetic
retinopathy [33]. To evaluate the quality and quantity of the
images they carried out different methods.
As a conclusion about this research, researchers developed
the model using GAN to generate retinal vessels synthetics
images. Even though they produced some good quality
images, the knowledge of the GAN is limited. As they
trained the GAN using only 614 images and that also
retrieved form one database [33]. And researchers
mentioned that the future extension of this research as they
going to trained the model with large scale data sets form
different databases. The size of the synthetic images (256 ×
256) is far from the resolution provided by images produced
by current retinal fundus image acquisition systems. And
these drawbacks can be solved if they using large amount of
data.
As mentioned previously the need of generated data is in
demand for researchers. And to contribute that another
research was done using two stage pipeline for generating
synthetics medical images. To test that they used to generate
retinal synthetic images. In their research they used dual
GAN to generate images [19].
In their two stage pipeline the first one is to produce
segmentation masks that represent the variable geometries
of the dataset, and the second one is to translate the masks
produced in Stage-I to photorealistic images. For the
training and testing they used DRIVE database for stage one
GAN. And it contains forty pairs of retinal fundi images and
segmentation masks extracted manually by two experts
[19]. For stage two they used with segmentation masks,
derived from a CNN segmentation network on the
MESSIDOR database. Stage one GAN is to generate
variable segmentation masks. It is based on the deep
convolutional generative adversarial network (DCGAN)
architecture, and built on the TensorFlow platform [19].
And stage two also build on the TensorFlow. To improve
the realistic of the image they used the u-net. Generation
mask given a photorealistic medical image. The u-net
architecture, specifically formulated for biomedical image
segmentation, is derived from an auto encoder architecture
that relies on unsupervised learning for dimensionality
reduction.
They evaluated the u-net on test images from the DRIVE
database and compared them with the ground truth to
calculate an F1 score. Also calculated the variance between
the 4 synthetic and real datasets through a Kullback–Leibler
(KL) divergence score [19]. They received an F1 accuracy
rating of 0.8877 for synthetic data and an F1 accuracy of
0.8988 on the DRIVE dataset. When testing variance,
received a KL-divergence score of 4.752 [19].
As a conclusion they used dual GAN models to generate
medical images due to the extreme complexion in the
medical images. However, it is able to identify simple
features such as general color, shape, and lighting. But still
they need more variant and accurate real image data to
improve the dual GAN pipeline to generate more realistic
images.
Another similar kind of research done to synthesized
medical images by using GAN. As they also tried to solve
the lack of data problem in bioinformatics field. To
overcome this issues in their research they proposed a new
variant of GAN, which, in addition to synthesized medical
images, also generates segmentation masks for the use in
supervised medical image analysis applications.
To get maximum benefit from the generated images while
using that in supervised algorithms or deep learning tasks
it’s necessary to have a ground truth solution for any given
input image. So for that researcher used a modified GAN to
generate images as well as generate segmentation masks as
well [41]. So it will be easy for the discriminator to decide
whether the image is real or synthetic. That will improve the
learning of generator as well as discriminator networks.
Researcher used DCGAN architecture for this research.
They used tensorfolow implementation of DCGAN in this
research [41]. And they modified that architecture and
include support for the generation of segmentation masks
and increased the image resolution to 128x128.To evaluate
the model they used 3 fold cross validation on the SCR Lung
Database [41]. For the quantitative evaluation, they chose to
perform image segmentation using the U-Net fully
convolutional network architecture. They used the Nesterov
optimizer at a learning rate of 0.00001 for the segmentation
task, with a momentum of 0.99 and a weight decay of
0.0005 [4-].
They tested the model using real data, real and synthetic data
and synthetic data only. To evaluate the segmentation
results, we used the Dice coefficient and Hausdorff distance
metrics [41]. The results shown in table 1 for full training
set and in table 2 for reduce training set.
TABLE 1
Full training set results.
TABLE 2
Reduce training set results.
As a conclusion researcher mentioned that after using the
image segmentation they find out the images showing small
details and noises correctly than before in lung image
datasets [41]. That not shown in details when they using
only GAN. Also they found if the training time for GAN is
too short, generated images are not in a usable format for
later supervised trainings. Finding a suitable stopping point
for GAN training is still a hot topic of current research, as a
lower GAN loss during training typically does not indicate
higher image quality of the generated images. Overall they
did a research and proved that using GAN along with image
segmentation can generate more accurate image data sets.
A research conducted in Switzerland to create a tool using
GAN to generate medical data sets. As GAN shown
remarkable success in generate things and specially produce
data sets. As to evaluate the system they used to generate
medical time series data set for intensive care unit [39]. In
ICUs, doctors have to make snap decisions under time
pressure, where they cannot afford to hesitate. It is already
standard in medical training to use simulations to train
doctors, but these simulations often rely on hand-engineered
rules and physical props. Thus, a model capable of
generating diverse and realistic ICU situations could have
an immediate application, especially when given the ability
to condition on underlying ‘states’ of the patient. As a
solution they proposed a Recurrent GAN (RGAN) and
Recurrent Conditional GAN (RCGAN) to produce realistic
real-valued multi-dimensional time series, with an emphasis methods on classification problems to improve the accuracy
on their application to medical data [39]. of a well-sought class. First one is to remove border samples
The model presented in this work follows the architecture of between two categories, second one is reduce
a regular GAN, where both the generator and the dimensionality through feature selection, third one sacrifice
discriminator have been substituted by recurrent neural the accuracy of less-valuable classes. To train the model
networks. Therefore, researcher present a Recurrent GAN they used the Share2Quit dataset [42].
(RGAN), which can generate sequences of real-valued data, There are many existing methods to deal with this problem.
and a Recurrent Conditional GAN (RCGAN), which can However, their performance needs to be significantly
generate sequences of real-value data subject to some improved in practice. Their results show that applying each
conditional inputs [39]. And researchers evaluated their of these analysis methods improves classification accuracy
work by using some toy data sets. They used generated data of the well-sought class and proved the GANs can generate
to train the model and used real data to test the model many simulation data. Researchers carried out different
(TSTR) [39]. And then they used that in reverse to train the evaluations to get the better accuracy of the methods. They
model with real data and tested with synthetic data (TRTS). tried and check the accuracy before and after feature
In this research to generate icu data they used recently- selection by each time drop one feature, Excluding Border
released Philips eICU database. It contains around 200,000 Samples, Data Augmentation inclusion and Sacrificial
patients from 208 care units across the US, with a total of Boundary. They got around 87% accuracy after include the
224,026,866 entries divided in 33 tables. And for the segmented data and got high accuracy after the Sacrificial
research purpose they get only 4 main variables such as Boundary [42]. But due to the imbalanced of their training
oxygen saturation measured by pulse oximeter (SpO2), data they got some classes’ accuracies were poor.
heart rate (HR), respiratory rate (RR) and mean arterial
pressure (MAP). After preprocessing the data, they end up
with a cohort of 17,693 patients [39].
Suppose that the model has overfit, and most points in latent
space map to training examples. Then all the generated data
will be similar or same as the training data. And if suppose
model underfit then all the generated data will be totally
varying with training data in terms of distribution. To avoid
that hey compared the distribution of reconstruction errors
and compared the generated samples [39].
As a conclusion they created a tool to generate data sets
using RGAN. And they evaluated the model by generating
time series data sets for ICU. And the major finding of the
research is by generating labelled training data - by
conditioning on the labels and generating the corresponding Fig. 3 Accuracy level based on the size of data [42].
samples, anyone can evaluate the quality of the model using
the ‘TSTR technique‘, where they train a model on the
So researcher presented machine learning methods such as
synthetic data, and evaluate it on a real data. They have
removing noise, reducing the number of dimensions,
additionally illustrated that such a synthetic dataset does not
generating simulation data, and sacrificing the accuracy of
pose a major privacy concern or constitute a data leak for
other unimportant classes to improve the accuracy of
the original sensitive training data.
important class [42]. And they got good accuracy of
The primary goal of this research is to generate simulated simulated data as well and it given in image 3. In their future
data which is useful when only limited data is available. For work they going to try to improve the quality of augmented
that researcher took smoking cessation as a case study in this data.
research to generate data sets. Case study is to test a peer
recruitment strategy to increase access to a smoking
cessation resource (a technology-assisted tobacco IX PREVIOUSE WORKS TO GENERATE THINGS USING
GAN
intervention) [42]. As noted, a key challenge is that data is
limited in health interventions. Identifying ideal recruiters is After the remarkable success of GAN, it’s widely used in
therefore a classical classification problem. So researcher many industries to generate things. GAN used to generate
tried to augment the data for this case study to improve the images, text, music and many more things. So hear
efficiency of the classification algorithms. researcher going to discuss about the use of GAN in other
For that they introduce two techniques in this study to industries in terms of generate things. Research done and
augment the datasets. One is to change a very small set of proven that GAN can generate open-domain dialogue [18].
‘fields’ values randomly. And the second one is to augment
the data using GAN [42]. Also they proposed a few analysis
They proposed a solution using GAN to produce sequences
that are indistinguishable from human-generated dialogue
utterances. The aim of this research is to generating
meaningful and coherent dialogue responses given the
dialogue history. And they used the idea of adversarial
evaluation to train a discriminant function to separate
generated and true sentences, in an attempt to evaluate the
model’s sentence generation capability. And they got a good
accuracy levels and they used humans to validate the results
[18].
Another research done to improve the training of GAN for
image synthesis [6]. As GAN is more popular in image
generation field [7] [37][12][33][19]. Recent works has
shown that GANs can produce convincing image samples
on datasets with low variability and low resolution [9][34].
However, GANs struggle to generate globally coherent,
high resolution samples - particularly from datasets with
high variability. They construct a variant of GANs
employing label conditioning that results in 128 × 128
resolution image samples exhibiting global coherence. Also
they expand on previous work for image quality assessment
to provide two new analyses for assessing the
discriminability and diversity of samples from class-
conditional image synthesis models [6].
Hear in another research, researchers tried to generate high
quality samples of natural images. Building a model to
generate high resolution natural images has been a major
problem in computer vision [12]. Recent advancement of
GAN there is a new path open in computer vision to
generate images similar like real ones. Their approach is to
use a cascade of convolutional networks within a Laplacian
pyramid framework to generate images in a coarse-to-fine
fashion [12-]. At each level of the pyramid, a separate
generative convent model is trained using the GAN
approach. In a quantitative assessment by human evaluators,
their samples were mistaken for real images around 40% of
the time, compared to 10% for samples drawn from a GAN
baseline model [12]. They used 15 volunteers to evaluate the
quality of the images generated by model. And they found
that the images generated by their model are far better than
the standard GAN model.
There is an interesting and useful research done to generate
images from text. But for this task normal AI systems and
algorithms are still far from the goal [37]. But to solve this
issue they develop a novel deep architecture and GAN
formulation to effectively bridge these advances in text and
image modeling, translating visual concepts from characters
to pixels. Their main contribution in this work is to develop
a simple and effective GAN architecture and training
strategy that enables compelling text to image synthesis of
bird and flower images from human-written descriptions
[37]. And below image showing the Generated bird images
by interpolating between two sentences (within a row the
noise is fixed). In future work, they target to scale up the
model to higher resolution images and add more types of
text [37].
Fig. 4 Generated bird images using sentences [37].
GAN is famous to generate text data in handwritten format.
Already there are researches done to generate numbers in
hand written format [5][16]. From very early age humans
learn handwriting as a skill. This research deals with this
problem where an intelligent system tries to learn the
handwriting of an entity using GAN. The start to train the
model to generate alphabetic and then single word and then
list of words. For this task they proposed a modified
architecture of DCGAN to achieve this [5]. Also to achieve
faster learning they used the reinforcement method. Early
implementation of their algorithm illustrates a good
performance with MNIST datasets [5]. Also during
evaluation they tried to generate ascii and 0 -9 number data.
And the wide variation in style of handwriting produced a
wide range of different style images of the same digit [5].
Their model hopes to give new insights in this area and its
uses include identification of forged documents, signature
verification, computer generated art, digitization of
documents among others.
Another research done to generate language using GAN.
Training GANs for language generation has proven to be
more difficult, because of the non-differentiable nature of
generating text with recurrent neural networks [31]. In this
work, researcher shown that recurrent neural networks can
be trained to generate text with the use of GANs from
scratch using curriculum learning, by slowly teaching the
model to generate sequences of increasing and variable
length. They evaluate the model by generating 640
sequences from each model and measuring %-IN-TEST-n,
that is, the proportion of word n-grams from generated
sequences that also appear in a held-out test set [31]. They
found that training the generator for 50 iterations every 10
training iterations of the discriminator resulted in superior
performance [31]. They implemented and proved that their
approach vastly improves the quality of generated
sequences compared to a convolutional baseline.
X ADVANTAGES AND LIMITATIONS OF GAN
As a new framework GAN comes with advantages as well
as disadvantages. One of the major advantage is GAN
framework will work with any type of neural networks.
Anyone can implement GAN using conventional neural
networks, recurrent neural network or even advances deep
learning networks. Another advantage is Markov chains are
never needed [16] [4] [23] [3], only the conventional back
propagation is used to get gradients, and no external
interface needed during the training [16-]. In terms of actual
result GAN produce better generated samples than the other
methods [16]. There’s no need to design the model to obey
any kind of factorization. Any generator net and any
discriminator net will work. Compared to the PixelRNN, the
runtime to generate a sample is smaller. GANs produce a
sample in one shot, while PixelRNNs need to produce a
sample one pixel at a time [16] [3].Especially the generation
of HD data GAN perform better than PixelRNN and also
GAN does not limit the generation dimension. Which
increase the scope of the generated data samples in wide
range.
The generation process of GANs does not require tedious
sampling sequence, but can directly sample and predict new
samples, which improve the efficiency of generating new
samples [16]. In practice, the samples generated by GANs
are easy to understand for humans. For example, GANs can
generate very sharp and realistic images [2] [37] [23]. Not
only have GANs made great contributions to the
development of generative models, but they are also
meaningful and instructive for semi-supervised learning [3].
GAN have solved a lot of problems in terms of generative
models and brought a new in AI field, but they still have
limitations. GANs adopt the adversarial learning idea, but
convergence of the model and existence of equilibrium
point have not been proved yet [23]. During the training
process needs to ensure the balance and synchronization of
two adversarial networks. D needs to be synchronized well
with G. The key challenge is to keep both D and G
synchronized. And mainly G must not be trained too much
without updating D, in order to avoid “the Helvetica
scenario” in which G mood collapses too many values of z
to the same value of x [16] [23]. Mode collapse refers in
scenarios which generated samples have the similar
features. For example if the GAN generated images the
color or the texture are same in all generated samples.
.Another disadvantage is if the discriminator is week then
the generator also perform low. So in GAN its must to train
the discriminator to be more powerful with lot of generated
and real data samples. As GAN using the neural networks it
have the common defect called poor interpretability of
neural networks. To overcome these limitations there are
new techniques and variants of GAN were introduced and
it’s emerging continually. Wasserstein GAN [44], [23]
greatly overcomes the training instability problem, and
partially solves the collapse mode problem at the same time.
As similar like that there are variants of GAN models
introduced such as Semi-GAN, C-GAN, BiGAN, InfoGAN,
AC-GAN, SeqGAN, BEGAN [44] [23][4][3]. How to
completely avoid collapse mode and further optimize the
training process remains a research direction of GANs [23].
Furthermore, the theory about model convergence and the
existence of equilibrium point remain important research
subjects in the near future.
XI CONCLUSION
Researcher analyze and review about bioinformatics data,
legal and ethical issues while accessing EHR data and other
security issues such as data breaching and misusing.
Researcher explained about the current methods to stop data
breaching and security. Also explained about the struggles
researchers facing while accessing the medical data for
research purposes. Further in this paper, researcher survey
the state of the art of GANs. This model has been used in
many generative works including images, text, sound and
data. And got good feedback from scientist and researchers.
Basic concept of GAN is min-max game theory. And it
contain generator and discriminator networks. Best part of
this model is it can be develop using any type of neural
networks.
In addition this paper reviewed the researches done to
generate bioinformatics data for secondary purposes such as
research. Researcher review about image data generation
and EHR data generation as well. Additionally this paper
contain review about usage of GAN in other industries.
Further researcher analyses and review about GAN
advantages and disadvantages also explained about future
research direction of GAN as well. Researcher believes that
this review will provide valuable insights and serve as a
starting point for researchers to apply GAN to generate data
sets for their bioinformatics researches.
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