68
11, 2018
Why Deep Learning Is Changing the Way to
Approach NGS Data Processing: A Review
Fabrizio Celesti , Antonio Celesti, Member, IEEE, Jiafu Wan
and Massimo Villari, Member, IEEE
Abstract—Nowadays, big data analytics in genomics is
an emerging research topic. In fact, the large amount of
genomics data originated by emerging next-generation se-
quencing (NGS) techniques requires more and more fast
and sophisticated algorithms. In this context, deep learn-
ing is re-emerging as a possible approach to speed up the
DNA sequencing process. In this review, we specifically dis-
cuss such a trend. In particular, starting from an analysis
of the interest of the Internet community in both NGS and
deep learning, we present a taxonomic analysis highlighting
the major software solutions based on deep learning algo-
rithms available for each specific NGS application field. We
discuss future challenges in the perspective of cloud com-
puting services aimed at deep learning based solutions for
NGS.
Index Terms—Big data, biotechnology, deep learning, ge-
nomics, next-generation sequencing (NGS).
I. INTRODUCTION
OWADAYS, big data analytics in genomics is an emerg-
N ing research topic. Knowing the nucleotide sequence of
the genome of an organism is extremely important in various
biotechnological research fields. DNA sequencing is a molec-
ular biology process able to determine the right nucleotide se-
quence of a DNA molecule, which is constituted by the alterna-
tion of four nucleotides: adenine (A), thymine (T), guanine (G),
and cytosine (C). Information obtained from the DNA sequenc-
ing process are used for basic biological research and in other
Manuscript received July 5, 2017; revised December 29, 2017; ac-
cepted March 31, 2018. Date of publication April 12, 2018; date of current
version July 24, 2018. This work was supported by the Italian Healthcare
Ministry funded project “Do severe acquired brain injury patients benefit
from telerehabilitation? A cost-effectiveness analysis study,” under Grant
GR-2016-02361306. (Corresponding author: Antonio Celesti.)
F. Celesti is with the Department of Biomedical and Dental Sci-
ences and Morphological and Functional Images, University of Messina,
Messina 98125, Italy (e-mail: fabrizio.celesti@studenti.unime.it).
A. Celesti is with the MIFT Department, University of Messina, Messina
98166, Italy, with the Alma Digit Research Laboratory, Messina 98166,
Italy, and also with the BIG DATA Laboratory, National Interuniver-
sity Consortium for Informatics, Rome 00185, Italy (e-mail: acelesti@
unime.it).
J. Wan is with the School of Mechanical and Automotive Engineer-
ing, South China University of Technology, Guangzhou 510630, China
(e-mail: mejwan@scut.edu.cn).
M. Villari is with the MIFT Department, University of Messina, Messina
98166, Italy, with the IRCCS Centro Neurolesi “Bonino Pulejo,” Messina
98124, Italy, and with the Alma Digit Research Laboratory, Messina
98166, Italy (e-mail: mvillari@irccsme.it).
Digital Object Identifier 10.1109/RBME.2018.2825987
1937-3333 © 2018 IEEE. Personal use is permitted, but republication/redistribution requires IEEE permission.
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IEEE REVIEWS IN BIOMEDICAL ENGINEERING, VOL.
, Member, IEEE,
specific fields, such as comparative genomic, metagenomics, bi-
ological systematic, medical diagnosis, early detection of can-
cer, single nucleotide polymorphisms (SNPs) research, regula-
tion of gene expression, forensic biology, and many others. In re-
cent years, modern high-performance sequencing methods have
been developed. In such a context, next-generation sequencing
(NGS) indicates a number of different modern DNA sequencing
techniques that are applied, for example, for genome sequenc-
ing, genome resequencing, transcriptome profiling (RNA-Seq),
DNA-protein interactions (ChIP-sequencing), epigenome char-
acterization, etc. NGS solutions allow us to speed up DNA
sequencing tasks. Even though it is possible to analyze short
fragments of nucleic acids in a more efficient fashion, the pos-
sibility to carry out a large number of parallel sequencing tasks
causes a huge amount of genomics data that need to be stored
and processed in a short time. Therefore, the huge amount of
genomics data brought by NGS techniques are examples of
the well-known “big data” problem [1]–[3]. NGS allows re-
searchers to perform numerous parallel sequencing processes in
order to obtain a large number of sequences in a short time and
at low cost, compared to a traditional Sanger sequencing based
on chain-termination methods.
With the advent of NGS, one of the major challenges in
bioinformatics is to efficiently transform genomics big data into
valuable knowledge. In fact, on one hand, a key issue is repre-
sented by the complexity of errors that are generated by NGS
data, whereas, on the other hand, another issue is represented
by the processing of the huge amount of NGS data that require
a considerable execution time, making the old statistical ma-
chinery based algorithms not so efficient any more. In order to
address such issues, both industrial and scientific communities
are looking at deep learning solutions. Deep learning is a re-
search field of machine learning and artificial intelligence that
is based on different levels of representation, corresponding to
factors of hierarchy in which high-level concepts are defined on
low-level basis. Although, it was introduced by Ivakhnenko and
Lapa in 1965 [4], currently, it is re-emerging due to its potential
applications to solve many big data problems in different appli-
cation fields, including genomics. In fact, it allows researchers
to perform DNA sequencing tasks in a more efficient and faster
fashion than in the past.
Up to now, several surveys have been proposed regarding the
application of deep learning in bioinformatics. In this context, a
survey on deep learning in medical image analysis was proposed
in [5], whereas a survey of recent advances in deep learning
CELESTI et al.: WHY DEEP LEARNING IS CHANGING THE WAY TO APPROACH NGS DATA PROCESSING: A REVIEW
techniques for electronic health record analysis was proposed
in [6]. However, a survey specifically focusing on the adoption
of deep learning based software tools in the NGS domain is
still missing. In this review, different from existing surveys,
we aim to overcome such a gap in the literature. In particular,
starting from a Google Trends analysis of the interest of the
Internet community in both NGS and deep learning and from
an analysis of scientific works available in the literature, we
present a taxonomic analysis of the current state of the art on
deep learning based solutions for NGS big data analytics. For
the sake of simplicity, in the rest of the paper, we will refer to
such a kind of software family with the term “deep learning
NGS” (DLN). In particular, besides highlighting the countries
where such a trend is more evident, we highlight the major NGS
application fields in which DLN software tools are available.
The remainder of the review is organized as follows. In
Section II, we motivate why deep learning is so important in
the field of NGS. An analysis on the interest of the Internet
community on such topics is provided in Section III. A taxo-
nomic analysis of DLN software tools is discussed in Section III.
A discussion on the current state of the art and future challenges
in the perspective of DLN cloud-based services is provided in
Section V. Section VI concludes the paper.
II. WHY DOES NGS REQUIRE DEEP LEARNING?
In this section, we motivate why deep learning is so important
in the field of NGS in order to introduce the reader toward
a taxonomic analysis of existing related works and initiatives
available in the literature.
DNA sequencing is the process of determining the precise
order of A, T, G, and C nucleotides within a DNA molecule.
The advent of DNA sequencing methods has greatly accelerated
biological and medical research works and discoveries. Knowl-
edge of DNA sequences is fundamental for basic biological
research and in various applied fields, including genome
analysis and SNP research (e.g., diagnostic approaches and
prevention, analysis structure of mutant proteins), comparative
genomics (e.g., metagenomics, ribosomal RNA (rRNA)
classification, infectious disease diagnostics), regulation of
gene expression (e.g., role of messenger RNA (mRNA) and
noncoding RNA), forensic biology, biological systematic, early
detection of cancer, virology, etc. Modern DNA sequencing
technologies have allowed researchers to efficiently analyze the
genomes of various living species, including humans, animal,
plant, and microbial organisms. Several new methods for DNA
sequencing were developed in 90 s and have been implemented
in commercial DNA sequencers since 2000.
NGS, also known as high-throughput sequencing, is a catch-
all term used to describe different modern DNA sequencing
technologies, including Illumina (Solexa) sequencing, Roche
454 sequencing, Ion torrent: Proton/PGM sequencing, and
SOLiD sequencing. NGS technologies allow researchers to se-
quence DNA much more quickly and cheaply compared to the
older Sanger sequencing technology and, as such, have revolu-
tionized the study of genomics and molecular biology.
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69
With the advent of NGS, one of the major challenges in bioin-
formatics has been to efficiently transform genomics big data
into valuable knowledge. In fact, on one hand, the key issue of
NGS is represented by the complexity of errors that are gener-
ated and that have to be managed during genomics big data pro-
cessing. For example, current error rates can vary roughly from
<1% for germline SNPs to >25% somatic INDELs; whereas,
on the other hand, the processing of genomics big data coming
from NGS requires a considerable execution time, making the
old statistical machinery based algorithms not so efficient any
more. In this regard, both industrial and scientific communities
have look at deep learning solutions that allow to perform NGS
data processing tasks faster than in the past.
Nowadays, deep learning is one of the strategic technology
trends reported by Gartner in 2017 [7]. It represents a class of
machine-learning (ML) algorithms that uses different abstrac-
tion levels to give a meaning to data, in which each level takes
input from the previous one [8]. Currently, it is used to address
problems in various application fields, including, e.g., complex
networks [9], finance [10], cancer prediction [11], satellite im-
age processing [12], image classification [13], social networks
data analysis [14], real-time video streaming [15], [16], cloud
management [17], etc. It was born from the artificial neural
networks (ANNs) research in order to improve the poor perfor-
mance of back-propagation algorithms when it is necessary to
consider networks with many hidden layers [18]. Algorithms can
be either supervised or unsupervised. Commonly, deep learning
algorithms are used to solve signal processing, graphical mod-
eling, and pattern recognition problems. Typical deep learning
methods include the following.
1) Deep neural network (DNN): It is an ANN with mul-
tiple hidden layers between the input and output layers,
which can model complex nonlinear relationships. Archi-
tectures generate compositional models where the object
is expressed as a layered composition of primitives.
2) Convolutional neural network (CNN): It is a class of deep,
feed-forward ANNs that has successfully been applied
to analyze images. CNNs use a variation of multilayer
perceptrons (MLPs) designed to require minimal prepro-
cessing. They are also known as shift invariant (or space
invariant) ANN, based on their shared-weight architec-
ture and translation invariance characteristics.
3) Recurrent neural network (RNN): It is a class of ANN in
which connections between units form a directed cycle
that allows us to analyze a dynamic temporal behavior.
Unlike feed-forward ANNs, RNNs can use their internal
memory to process arbitrary sequences of input.
4) Autoencoder (AE): It is an ANN used for unsupervised
learning of efficient codings. Four main variants exist as
follows:
a) Sparse autoencoder (SA): By imposing sparsity
on the hidden units during the training process
(while having a larger number of hidden units than
inputs), an AE can learn useful structures in the
input data. This allows sparse representations of
inputs.
70 IEEE REVIEWS IN BIOMEDICAL ENGINEERING, VOL. 11, 2018

Fig. 1. Google Trends. Interest during the time period ranging from the week of December 18–25, 2011 to the week of December 4–10, 2016.

b) Denoising autoencoder (DA): It takes a partial cor- TABLE I

GOOGLE TRENDS: INTEREST OF THE INTERNET COMMUNITY IN NGS AND
rupted input while it trains to recover the original DEEP LEARNING DURING THE TIME PERIOD RANGING FROM THE WEEK OF
undistorted one. DECEMBER 18–25, 2011 TO THE WEEK OF DECEMBER 4–10, 2016
c) Variational autoencoder (VA): It inherits the AE
architecture, but makes strong assumptions con-
cerning the distribution of latent variables.
d) Contractive autoencoder (CA): It adds an ex-
plicit regularizer in its objective function that
forces the model to learn from slight variations of
input values.
Apart from the aforementioned methods, several variants have
been proposed so far.
The research on deep learning has demonstrated success in
various application fields including, among others, healthcare
and biotechnology. Considering applications of deep learning
in healthcare, a hidden Markov model (HMM) enriched by a
feed-forward neural network was applied for speech recogni-
tion in [19]. Moreover, the interest for deep learning for speech
recognition was also shown by Microsoft in [20]. A CNN-based
method for determining the author’s personality studying the
text was reported in [21]. Other relevant applications of deep
learning in healthcare regarded mammography [22] and analysis
of molecules for discovering new drugs [23]. Regarding genet- Fig. 2. Google Trends. Distribution on map of the interest in deep
ics and genomics problems, AE methods were used to predict learning in the considered time period.
gene ontology annotations and gene-function relationships. In
general, deep learning methods are very useful in the following
conditions: III. INTEREST OF THE INTERNET COMMUNITY IN NGS AND
1) there are genomics big data (e.g., > 50 k samples and DEEP LEARNING
> 1M ideals; In recent years, we have observed a constant interest of the
2) there are high-quality input data and labels for training; Internet community in NGS and an increasing interest in deep
3) the mapping from data and labels is unknown but defi- learning. Fig. 1 shows the interest of the Internet community in
nitely exists; and NGS and Deep Learning according to Google Trends during the
4) there are problems hard to be solved with classical statisti- time period ranging from the week on December 18–25, 2011
cal and ML approaches, in which the analysis of previous to the week on December 4–10, 2016. As shown in Table I,
high-quality results can improve the training task. numbers represent the interest of searching the terms NGS and
Considering the latter, the deep learning approach well fits deep learning with respect to the highest point of the graph
the SNP and INDEL calling from NGS big data. In particular, according to a region in a considered period. The 100 value
figuring out the true genome sequence derived from NGS big indicates the greatest term search frequency, 50 indicates the
data, there is a computational and statistical challenge if we metaterm search, whereas 0 indicates a term search frequency
consider that actual sequencer output includes roughly 1 billion less than 1% with respect to the greatest search frequency. We
basepair long DNA reads (i.e., 30 per coverage) and that a can observe that even though the interest on NGS has been
true genome sequence includes 3 billion bases in 23 contiguous constant since 2011, in the last years, there was a meaningful
chunks (i.e., chromosomes). Moreover, a complex error process increase of the interest in deep learning. Figs. 2 and 3 depict
makes it difficult to call variants accurately in NGS big data. the interest of Google users, respectively, in NGS and deep
In the following, we will provide a comprehensive taxonomic learning, considering different geographical areas. Considering
analysis of deep learning based solutions in the NGS domain. both maps, we can notice that there are peaks of users interested

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CELESTI et al.: WHY DEEP LEARNING IS CHANGING THE WAY TO APPROACH NGS DATA PROCESSING: A REVIEW
Fig. 3. Google Trends. Distribution on map of the interest in NGS in
the considered time period.
in both NGS and deep learning in the United States, Italy, United
Kingdom, Germany, and India.
Looking at Figs. 2 and 3, it is evident how, according to
Google Trends, the Internet community interested in both NGS
and deep learning come from the United States, United King-
dom, Italy, Germany, and India.
IV. TAXONOMIC ANALYSIS OF SCIENTIFIC INITIATIVES
The huge amount of information obtained by means of the
NGS technologies must be stored and analyzed in a proper man-
ner. Therefore, many software solutions are available for these
purposes. In particular, hereby, we focus on deep learning based
software solutions for big NGS data analytics (which we call
DLG) [24]. In order to analyze the state of the art, we considered
databases, PubMed, Web of Science, and Scopus, that include
papers coming from over 5000 of the major publishers spread
all over the world [25]. In particular, in our search, we combined
the “deep learning” and “NGS” terms. Although at the time of
writing of this review, we found more than 28 000 records, only
a few of them specifically focused on DLN software solutions.
From a taxonomic analysis of the state of the art, the major
NGS application fields in which deep learning has been adopted
so far includes the following:
1) regulation of gene expression (including epigenetic mod-
ifications, interactions between proteins and regulatory
sequences, and prediction of splicing variants of mRNA);
2) genome analysis and SNPs research (including SNPs in
coding and noncoding regions of genome, and protein
structure prediction); and
3) early detection of cancer (including research and moni-
toring of biomarkers) [26]–[28].
Regulation of gene expression is on the basis of the correct
progress of all biological functions, which are finely adjusted.
In this regard, an important mechanism involved in it considers
epigenetic modifications (such as DNA methylation and histone
modifications), which affect gene expression without changing
the nucleotide sequence of the genome. In addition, it is also
important that the correct interaction of the DNA with spe-
cific proteins as the transcription factors (TFs) is responsible
for the transcription of DNA into RNA, in a specific-sequence
manner. Even the alternative splicing, responsible for the syn-
thesis of various mRNA from a gene, is an important regulatory
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71
mechanism. Furthermore, mutations in specific regulatory se-
quences are on the basis of the alteration of these cellular pro-
cesses that could compromise cell vitality.
Genome analysis and SNP research have the objective to
identify polymorphisms in the genome (in particular, SNPs that
could be associated with diseases). Accordingly, it is possible
to develop new diagnostic approaches and increase resources
in disease prevention. In addition, the knowledge of polymor-
phisms in the coding regions of DNA allows the prediction of
conformational structures of proteins that should be encoded.
Early detection of cancer is extremely important to fight
diseases caused by an abnormal cell proliferation caused by
genetics anomalies. Furthermore, it is also important for the
administration of the most appropriate medical treatments.
Fig. 4 shows a taxonomic tree related to the major DLN soft-
ware solution currently available over the Internet. In particular,
nodes represent the NGS application fields, whereas leaves rep-
resent the adopted DLN software solution. Furthermore, Table II
summarizes, for each NGS application field, the major recent
DLN software solutions, bibliographic references, title of sci-
entific works, adopted deep learning methods, and countries
of origin.
A. Epigenetic Modifications
Deepmethyl [29] is stacked denoising autoencoder (SDA)
based piece of software aimed at predicting the methylation
state of DNA CpG dinucleotides by adopting features inferred
from a three-dimensional genome topology (based on Hi-C)
and patterns of DNA sequences. DeepChrome [30] is a piece
of framework based on CNN able to classify gene expression
using, as input, histone modification data. It enables automatic
extraction of complex interactions. In addition, in order to simul-
taneously display the combinatorial interactions among histone
modifications, it adopts a novel optimization based technique
that generates feature pattern maps.
B. Proteins and Regulatory Sequences and DNA
Binding Proteins
Basset [31] is an open source software package based on
CNN that is able to learn the functional activity of DNA se-
quences analyzing genomics data. Basset was tested on a com-
pendium of accessible genomic sites mapped in 164 cell types
by DNA sequencing in order to demonstrate greater predic-
tive accuracy compared to other methods. Deep Motif (DeMo)
[32] is a dashboard toolkit that provides a suite of visualiza-
tion strategies in order to extract Motifs, or sequence patterns
from DNN models for TF binding classification. DanQ [33]
is a piece of hybrid framework able to predict new noncoding
functions from sequences. It combines CNNs and bidirectional
long short-term memory network (BLSTM), which is a variant
of the RNN that combines the outputs of two RNNs, one pro-
cessing the sequence from left to right, the other one from right
to left. PEDLA [34] is a piece of framework based on DNN
and HMM, which can directly learn an enhancer predictor from
a huge amount of heterogeneous genomics data and is able to
apply generalization strategies with the purpose to be mostly
72 IEEE REVIEWS IN BIOMEDICAL ENGINEERING, VOL. 11, 2018

Fig. 4. Taxonomic tree reporting the major DLN software tools.

consistent across various cell types and/or tissues. DECRES D. SNPs in Coding and Noncoding Regions of Genome
[35] is a supervised deep learning solution for the identification
DeepSea [41] is a piece of framework based on CNN algo-
of enhancer and promoter regions in the human genome. It com-
rithms that directly learns a regulatory sequence code from large-
bines the following deep learning basic and derived methods:
scale chromatin-profiling data and enables the prediction of
CNN, DA, CA, SDA, stacked contractive autoencoder (SCA),
chromatin effects of sequence alterations with single-nucleotide
multiclass logistic/softmax regression (MCL/SR), MLPs, re-
sensitivity. Diet networks [42] is a software tool based on the
stricted Boltzman machine (RBM), deep belief network (DBN),
concept of CNN reparameterization aimed at solving the over-
and stacked restricted Boltzman machine (SRBM). Flexible In-
fitting problem originated when the number of input features
tegration of Data with Deep LEarning (FIDDLE) [36] is an
can be orders of magnitude larger than the number of training
open source flexible integrative data-agnostic piece of frame-
examples. In particular, by means of a neural network parame-
work that is able to learn a unified representation by analyzing
terization, it is able to considerably reduce the number of free
multiple data types in order to infer another data type. DEEP
parameters. It is based on the idea that it can first learn and pro-
[37], [38] is a predictive piece of framework using the CNN
vide a distributed representation for each input feature (e.g., for
approach able to streamline the analysis of enhancer’s prop-
each position in the genome where variations are observed), and
erties in various cellular conditions. By using such a solution,
then learn by means of another neural network how to map each
it is possible to train many models of individual classification
distributed feature representation into a vector of parameters by
that can be combined to classify DNA regions as enhancers
means of a classifier neural network in which weights links each
or nonenhancers. DEEP uses features that are deduced from
value of the feature to a specific hidden unit.
histone modification marks or attributes coming from differ-
DANN [43] is a software tool aimed at annotating genetic
ent sequence characteristics. DeepBind [39] is a stand-alone
variants, especially noncoding variants, for the purpose of iden-
software tool based on CNN that is totally automatic and is
tifying pathogenic ones. It uses the same feature set and train-
able to handle millions of sequences for each experiment. The
ing data as combined annotation-dependent depletion to train a
specificities that are determined by DeepBind are displayed
DNN that can capture nonlinear relationships among features in
as a weighted position matrix or as a “mutation map,” which
an efficient fashion when there is large number of samples and
indicates how the variations affect binding within a specific
features.
sequence.
E. Protein Structure Prediction
C. Prediction of Splicing Variants of mRNA
Given enough large protein families and using a global statis-
DeepSplice [40] is a CNN-based solution adopted as a splice tical inference approach, it is possible to obtain enough accuracy
junction classification tool employing deepCNNs that offers the in protein residue contact predictions to predict the structure of
following: many proteins. However, these approaches do not consider the
1) offers better performances compared to other methods fact that the contacts in a protein are neither randomly nor
for predicting splice sites; independently distributed, but actually follow precise rules gov-
2) offers high computational efficiency; and erned by the structure of the protein, and thus, are interdepen-
3) can be applied so as to pick out self-defined training data. dent. Considering such a concept, PconsC2 [44] is a multilayer

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CELESTI et al.: WHY DEEP LEARNING IS CHANGING THE WAY TO APPROACH NGS DATA PROCESSING: A REVIEW 73

TABLE II
RELATED WORK TITLE, AUTHORS, COUNTRY, AND DEEP LEARNING BASED SOLUTION FOR EACH NGS SUBFIELD

feed-forward (MLFF) stack of random decision forests learn-
ers aimed at identifying proteinlike contact patterns in order to
improve contact predictions.
F. Research and Monitoring of Biomarkers
Cancer detection from gene expression data is a challenge
due to the high dimensionality and complexity of considered
data. After decades of research, there is still uncertainty in the
clinical diagnosis of cancer and the identification of tumor-
specific markers. The stacked denoising AE (SDAE) solution
[45] adopts a deep learning approach aimed at cancer detection
from gene expression data identifying genes that are critical for
the diagnosis of breast cancer.
V. DISCUSSION AND FUTURE CHALLENGES
From both Google Trends and taxonomic analysis of aca-
demic initiatives, it is evident that deep learning for the process-
ing of NGS big data is an emerging research topic.
Fig. 5 highlights that the highest percentage of DLN software
tools is available in the United States, confirming the interest
of the Internet community of this country on deep learning and
NGS. From an academic point of view, other relevant initiatives

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74
Fig. 5. Percentage of deep learning based NGS tools according
to country.
Fig. 6. Percentage of deep learning based tools according NGS
subarea.
were developed in Canada, China, Sweden, and Saudi Arabia.
Instead, Fig. 6 highlights that 50% of analyzed deep learning
tools are aimed at proteins and regulatory sequences that re-
sults the major NGS subfield, which is currently more treated,
followed by epidemic modification (12.5%). Other NGS fields
that currently are not covered by deep learning based solutions
include comparative genomics (e.g., metagenomics, rRNA clas-
sification, and infectious disease diagnostics), forensic biology,
biological systematic, and virology.
Regarding deep learning methods, the most used DLN soft-
ware tools are CNN, DNN, HMM, and SDA. The major one
is CNN, which is used in DeepChrome, Basset, FIDDLE,
DEEP, DeepBind, DeepSlice, DeepSea, and Diet software tools;
whereas, variants are used in DeMo and DanQ software tools.
The DNN method is used in DANN and PEDLA in combina-
tion with HMM. SDA is used in Deepmethyl and SDAE. In the
end, MLFF, derived from CNN, is used in PconsC2. A partic-
ular consideration deserves DECRES that combines different
deep learning methods including CNN, DA, CA, SDA, SCA,
MCL/SR, MLP, RBM, DBN, and SRBM.
Cloud computing is emerging as a promising solution for the
fast on-demand data processing in distributed systems, thanks
to its theoretical infinite availability of storage and computa-
tion resources. The adoption of such a paradigm opens toward
new business opportunities [46], besides bringing different ad-
vantages in terms of service discovery [47] and security [48].
The advent of this paradigm is changing the way of conceiv-
ing information systems in different application fields, including
biotechnology. From our analysis, even though cloud computing
based NGS solutions [49] exist, currently it is evident how DLN
software tools are currently provided in form of stand-alone ap-
plications and not in an “as a service” form. DLN software tools
could benefit of cloud service levels including Platform as a
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IEEE REVIEWS IN BIOMEDICAL ENGINEERING, VOL. 11, 2018
Service (PaaS) [50] and Software as a Service (SaaS) [51]: The
first provides a global application development and deployment
environment to software developers [cloud providers typically
offer development toolkit through application program interface
(API)]; the second provides applications by means of web inter-
faces. Currently, there are many frameworks that are used to run
parallel algorithms in cloud computing systems. An example is
Apache Hadoop, which is used to run distributed parallel pro-
cessing clusters on top of a scalable virtual infrastructure. In this
regard, we underline that DNA sequencing and the NGS data
processing are typical problems that can be solved by means of
parallel deep learning algorithms.
Future challenges regard the interoperability among heteroge-
neous bioinformatics cloud providers aimed at providing DLN
in form of PaaS and SaaS, which is the ability of information
systems and software applications to communicate each other
and exchange data [52]. Unfortunately, most existing NGS li-
brary preparation devices, sequencing instruments, and software
tools have not been designed to work in a clinical networked
environment even if an interoperable world-wide ecosystem of
cooperating bioinformatics clouds would bring benefits for the
whole research community. In our opinion, evolved federated
PaaS aimed at DLN could push the development of new mash-
up DLN SaaS. However, in order to achieve such a scenario, the
research community has to define the following:
1) common standard communication interfaces to enable the
communication between different federated bioinformat-
ics cloud providers;
2) common standard DNA sequencing data format;
3) common PaaS development and deployment environment
for DLN SaaS solutions exploiting the advantages of
cloud computing in terms of system scalability, data pro-
cessing, and security; and
4) common standard APIs for the development of DLN SaaS
solutions.
VI. CONCLUSION
Deep learning for big data analytics in genomics is an emerg-
ing research topic. In this review, we specifically focused on
deep learning adopted for NGS. Although deep learning was
introduced in 1965, currently it is re-emerging to solve big
data problems in genomics. In particular, first, by means of
the Google Trends tools, we analyzed the interest of the Inter-
net community on NGS and deep learning topics in a period
starting from December 2015 to December 2016, highlighting
how the interest in the latter is constantly growing. Second, we
presented a taxonomy in order to analyze the current state of
the art of DLN software solutions. From our study, we realized
that deep learning software tools are at an early stage. Many
researchers are beginning to look at deep learning especially in
context of regulatory sequences and DNA binding proteins, but
there are not yet so many solutions focusing on other genomics
research fields. Moreover, from our analysis, it is evident how
deep learning is currently adopted in NGS stand-alone applica-
tions and not in cloud computing PaaS and SaaS. In our opinion,
the research community could benefit of the advantages offered
CELESTI et al.: WHY DEEP LEARNING IS CHANGING THE WAY TO APPROACH NGS DATA PROCESSING: A REVIEW
by future cloud computing services based on deep learning al-
gorithms in terms of both computational resource scalability
and DNA fragments data sharing. With this review, we hope we
succeeded in stimulating the biotechnology community toward
the development of advanced DLN software tools.
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Fabrizio Celesti received the master’s degree
in biotechnology from the University of Messina,
Messina, Italy, in 2017. He is currently work-
ing toward the second-level master postgradu-
ate course in advanced medical biotechnology
for diagnostic in laboratory at the Department of
Biomedical and Dental Sciences and Morpho-
functional Images, Messina University.
Since 2016, he has collaborated with the De-
partment of Engineering on research activities
on big genomics data analytics. Since 2016, he
has been a Technical Program Committee member of the IEEE ICT so-
lutions for eHealth (ICTS4eHealth). His main research interests include
ehealth, genomics, and big data analytics.
Antonio Celesti (M’16) received the master’s
degree in computer science in 2008, and the
Ph.D. in advanced technologies for informa-
tion engineering in 2012, from the University of
Messina, Messina, Italy. He is currently an Ad-
junct Professor in databases with the University
of Messina. He has been a collaborator in many
national and international projects, such as the
EU FP7 Project RESERVOIR—Resources and
Services Virtualization Without Barriers, from
2008 to 2011, and the EU FP7 Project VISION
CLOUD—Cloud Virtualized Storage Services Foundation for the Future
Internet, from 2010 to 2013. From 2012 to 2014, he was an Assistant Re-
searcher with the University of Messina working on the POR FSE 2007–
2013 Project SIMONE, focusing on energy management and cloud com-
puting. Since 2012, he has been responsible for the Digital Iconographic
Atlas of Numismatics in Antiquity. Since 2014, he has been an Assistant
Researcher with the University of Messina working on the EU FP7 project
FrontierCities—European Cities Driving the Future Internet. From 2015
to 2016, he was a collaborator in the EU Horizon 2020 Project BEACON,
focusing on federated cloud networking. Since 2017, he has been a Prin-
cipal Investigator of the Horizon 2020 Project FrontierCities2 subgrant
CASMOB and responsible for the University of Messina with the Project
entitled “Do severe acquired brain injury patients benefit from Telere-
habilitation? A cost-effectiveness analysis study,” funded by the Italian
healthcare industry. He has co-authored many scientific publications on
distributed systems and cloud computing. His main research interests
include distributed systems and cloud computing (with particular regard
to federation, storage, security, and energy efficiency), and assistive
technology.
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IEEE REVIEWS IN BIOMEDICAL ENGINEERING, VOL. 11, 2018
Jiafu Wan (M’11) has been a Professor with
the School of Mechanical and Automotive En-
gineering, South China University of Technol-
ogy, Guangzhou, China, since September 2015.
He has directed 16 research projects, including
the National Key Research and Development
Project, the National Natural Science Founda-
tion of China, the High-level Talent Project of
Guangdong Province, and the Natural Science
Foundation of Guangdong Province. His re-
search interests include cyber-physical systems,
intelligent manufacturing, big data analytics, Industry 4.0, smart factory,
cloud robotics, and Internet of vehicles.
Prof. Wan is an Associate Editor for the IEEE ACCESS (SCI) and on
the Editorial Board of PLoS One (SCI), and he is a Managing Editor for
the International Journal of Autonomous and Adaptive Communications
Systems (Ei Compendex) and International Journal of Applied Research
and Technology (Ei Compendex). He has been a Leading Guest Editor
for several SCI-indexed journals, such as IEEE SYSTEMS JOURNAL, IEEE
ACCESS, Computer Networks (Elsevier), Mobile Networks & Applications
(Springer), Computers and Electrical Engineering (Elsevier), and Micro-
processors and Microsystems (Elsevier). He is a senior member of both
CMES and CCF.
Massimo Villari (M’08) received the Laurea
degree in 1999 in electronic engineering, and
the Ph.D. in advanced technologies for informa-
tion engineering in 2002, from the University of
Messina, Messina, Italy. He is currently an As-
sociate Professor in computer engineering with
the University of Messina. He is actively work-
ing as an IT Security and Distributed Systems
Analyst in cloud computing, virtualization, and
storage. For the EU Project RESERVOIR, he
led IT security activities, and for the EU Project
VISION-CLOUD, he covered the role of architectural designer for the
University of Messina. He is currently working on the EU Project Fron-
tierCities, the Accelerator of FIWARE on Smart Cities—Smart Mobility,
where he is responsible for information and communications technology.
He is strongly involved in EU Future Internet initiatives, specifically cloud
computing and security in distributed systems. He has been a co-author
of more than 130 scientific publications and patents on cloud comput-
ing (cloud federation), distributed systems, wireless networks, network
security, cloud security, and cloud and IoTs. He was a General Chair
of ESOCC 2015 and IEEE-ISCC 2016. Since 2011, he has been a fel-
low of IARIA, recognized as a cloud computing expert, and has also
been involved in the activities of the FIArch, the EU Working Group on
Future Internet Architecture. In 2014, he was recognized by an inde-
pendent assessment (IEEE TRANSACTIONS ON CLOUD COMPUTING, April
2014) as one of the worldwide active scientific researchers, top 27 clas-
sification, in the cloud computing area. He has been a General Chair of
EAI-CN4IoT. He is an Editor-in-Chief of the EAI-endorsed Transactions
on Smart Cities. He is currently the scientifist responsible for research
activities on Cloud and eHealth agreed upon between the University
of Messina and IRCCS Centro Neurolesi “Bonino Pulejo” in eHealth:
http://healthycloud.irccsme.it/.