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Big data analytics for personalized medicine
Davide Cirillo1 and Alfonso Valencia1,2
Big Data are radically changing biomedical research. The
unprecedented advances in automated collection of large-
scale molecular and clinical data pose major challenges to data
analysis and interpretation, calling for the development of new
computational approaches. The creation of powerful systems
for the effective use of biomedical Big Data in Personalized
Medicine (a.k.a. Precision Medicine) will require significant
scientific and technical developments, including infrastructure,
engineering, project and financial management. We review
here how the evolution of data-driven methods offers the
possibility to address many of these problems, guiding the
formulation of hypotheses on systems functioning and the
generation of mechanistic models, and facilitating the design of
clinical procedures in Personalized Medicine.
Addresses
1
Barcelona Supercomputing Center (BSC), C/Jordi Girona 29, 08034,
Barcelona, Spain
2
ICREA, Pg. Lluı́s Companys 23, 08010, Barcelona, Spain
Corresponding author: Cirillo, Davide (davide.cirillo@bsc.es)
Current Opinion in Biotechnology 2019, 58:161–167
This review comes from a themed issue on Systems biology
Edited by Maria Klapa and Yannis Androulakis
https://doi.org/10.1016/j.copbio.2019.03.004
0958-1669/ã 0001 Elsevier Ltd. All rights reserved.
Introduction
In the last few decades, we have undergone an unprec-
edented transformation of biomedical research, conduct-
ing to a novel paradigm of data-driven biomedical science
complementing the well-developed hypothesis-driven
knowledge discovery [1]. Along with high-throughput
genome sequencing, marked by plummeting costs and
increasing availability, healthcare organizations have
started to embrace extraction of information from digita-
lized clinical records and imaging data. The outstanding
improvement in automated collection of massive data
volumes is exemplified by community movements such
as the Global Alliance for Genomics and Health
(GA4GH, www.ga4gh.org), research infrastructures like
ELIXIR [2] and Big Data to Knowledge (BD2K) [3], and
international initiatives such as the International Cancer
Genome Consortium (ICGC), the International Human
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Epigenome Consortium (IHEC), and the International
Rare Disease Consortium (IRDiRC), among others
(Table 1).
The accessibility to ‘big data’, a term first introduced in
1997 in the context of data visualization [4], sets down
both an exceptional and ambitious challenge for biomed-
ical research, with special emphasis on Personalized
Medicine [5]. A typical portrait of biomedical big data
features heterogeneous, multi-spectral, incomplete, and
imprecise observations [6]. Hence, data-intensive analyt-
ics require ad hoc capabilities for complex data represen-
tation and modeling, algorithmic optimization, and
computational power. In healthcare, for instance, such
systems are defined by five distinctive capabilities: pat-
terns of care identification, unstructured data analysis,
decision support, prediction, and traceability [7].
Nonetheless, data gathering moves faster than both
data processing and data analysis, emphasizing the
widening gap between the rapid technological progress
in data acquisition and the comparatively slow func-
tional characterization of biomedical information [8]. In
this regard, the integration of molecular information,
such as multi-omics data, and the phenotypic informa-
tion of individual patients from electronic health
records (EHRs), is becoming of critical importance.
Considering the relevance of biomedical data protec-
tion, efficient and secure models for storage, integra-
tion, data-driven discovery, and interpretation must
distinguish big data analytics systems for Personalized
Medicine. In the following, we review the main types
and systems for big data management, analysis, and
interpretation in Personalized Medicine.
Data types
Routinely collected patient information is gaining volume
and complexity. For instance, neuroimaging is currently
producing more than 10 petabytes of data every year with
a staggering ninefold increase in data complexity (i.e. data
acquisition modalities) over the last three decades [6]. In
parallel, genomic data alone are expected to reach exas-
cale dimensions by the next decade, largely exceeding
other big data areas such as astronomy [9]. Strikingly,
these data represent a tiny fraction of the over 2.5 quintil-
lion bytes (2.3 trillion gigabytes) of information generated
every day [10].
Among big data types, imaging data can be considered the
largest in volume as it covers not only gigapixel images,
showing tissues and organisms at subcellular resolutions,
Current Opinion in Biotechnology 2019, 58:161–167
162 Systems biology
Table 1
Large international consortia focusing on Personalized Medicine
Initiative
Human Genome Diversity Project (HGDP)
Global Network of Personal Genome Projects (PGP)
The Encyclopedia of DNA Elements (ENCODE)
The NIH Roadmap Epigenomics Mapping Consortium
(Roadmap)
International Human Epigenome Consortium (IHEC)
Cohorts for Heart and Aging Research in Genomic
Epidemiology (CHARGE)
International Cancer Genome Consortium (ICGC)
The Cancer Genome Atlas (TCGA)
International Rare Disease Consortium (IRDiRC)
but also metadata and quantitative measurements. In this
view, the development of integrative platforms for scal-
able analysis of imaging data coupled with genetic and
functional annotations are of utmost importance [11].
Health information in digital format includes also the
structured (e.g. ICD codes) and unstructured (e.g. symp-
toms descriptions) content of EHRs, initially designed to
communicate information between clinicians, represent-
ing a valuable resource for research and model develop-
ment [12]. Concurrently, massive parallel quantification
technologies of genomic data, such as whole-genome
sequencing (WGS) and whole-exome sequencing
(WEX), are playing a key role in accelerating data-driven
biomedical discovery. Along with genome sequencing,
experimental platforms such as transcriptome sequencing
(RNA-seq and ribosome profile), proteome profiling (mass
spectrometry) and interactome profiling (chromosome con-
formation capture, ChIP-seq, hybrid assays), are making
biomedical information accessible faster and cheaper [13].
Recent advances in genomics, including single-cell
genome and transcriptome sequencing [9], circulating
tumor DNA (ctDNA) identification through liquid biopsy
[14], and sequencing of bacterial genomes in human sam-
ples (metagenomics), are already having a great impact in
medicine, and are destined to be integrated in standard
medical practice. In particular, long-read sequencing has
proved successful for microbial composition analysis and de
novo genome assembly, especially in combination with
short-read sequencing and optical maps [15].
Together with imaging, multi-omics data, and EHRs,
patient generated health data (PGHD), from wearable
and implantable devices, is becoming an increasingly
relevant big data type in Personalized Medicine [16].
Health and treatment history as well as lifestyle choices,
tracked through mobile apps, guarantee patient engage-
ment, which is crucial to improve the quality of healthcare
services [12]. Moreover, real-time sensor devices for
biometric measurements are promoting developments
Current Opinion in Biotechnology 2019, 58:161–167
Research focus Link
General www.hagsc.org/hgdp/
General www.personalgenomes.org/
General www.encodeproject.org/
General www.roadmapepigenomics.org/
General http://ihec-epigenomes.org/
Cardiovascular and www.chargeconsortium.com/
age-related diseases
Cancer https://icgc.org/
Cancer https://cancergenome.nih.gov/
Rare diseases www.irdirc.org/
in new areas such as stream computing, concerned with
processing and analysis of real-time flows of data [17].
Data management
Distinct areas in which big data are applied include drug
and biomarker development, and basic research in cancer,
rare diseases, neurodegeneration, diabetes, and cardiovas-
cular pathologies, among others [18]. The development of
these areas in the frame of Personalized Medicine is high in
social and governmental agendas, requiring large collabo-
rative efforts, collective expertise and distributed manage-
ment (Figure 1). Many are the examples of how large
international research platforms are committed to achiev-
ing Personalized Medicine solutions, such as personalized
brain models for patient with intractable epilepsy [19]
developed within the Human Brain Project (www.
humanbrainproject.eu), a Flagship initiative of the Euro-
pean Commission. The model of research-by-consortium,
initiated by community movements and increasingly
adopted by government agencies and industry, is at the
basis of all the large-scale biomedical projects, as in case of
the iconic Human Genome Project. For example, the
European Commission has invested more than s2.6 billion
in Personalized Medicine research through the FP7 and
Horizon 2020 programs [20], and launched the Interna-
tional Personalized Medicine consortium (PerMed), whose
success stories include BLUEPRINT project for the study
of epigenetic mechanisms of hematopoiesis [21]. National
funding, infrastructures, institutional support, public–pri-
vate consortia, and donations favor open access, user equity,
and sustainability, especially in the case of expert-curated
knowledgebases struggling with inappropriate funding
models [22]. Sustaining the biomedical big data ecosystem,
largely funded by short-term grants, demands coordinated
international efforts and an open discussion on future
directions and actions [23].
Biomedical big data exhibit unique features, such as
highly distributed acquisition, format heterogeneity,
and content sensitivity. In this regard, the General Data
Protection Regulation (EU) 2016/679 (GDPR), setting
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 Big data analytics for personalized medicine Cirillo and Valencia 163

Figure 1

CATALONIA SCOTLAND
Undiagnosed Rare Diseases The Scottish Genomes
Catalunya (URDCat) Partnership
Medicina Personalitzada a
Catalunya-Cancer (MedPerCan) ICELAND DENMARK
UNITED KINGDOM
deCODE genetics UK Biobank Genome Denmark
SPAIN Genomics England LUXEMBOURG
Spanish Undiagnosed Rare The National Centre of Excellence
FRANCE FINLAND in Research on Parkinson’s disease
Diseases Program (SpainUDP)
Médecine France FinnGen
NETHERLANDS
génomique 2025
Genome of the ESTONIA
Netherlands (GoNL) Estonian Biobank
CANADA (EGCUT)
Tomorrow Project
CZECH REPUBLIC
National Centre for
Medical Genomics

JAPAN
The Initiative on Rare and
Undiagnosed Diseases (IRUD)
SWITZERLAND
CHINA
Swiss Personalised
Health network (SPHN) China Kadoorie Biobank

UNITED STATES SINGAPORE

ITALY
Precision Medicine Initiative Singapore Genome
SardiNIA
(PMI) Cohort Program Variation Program
SAUDI ARABIA
Saudi Human
Genome Project

MEXICO AND LATIN AMERICA

Slim Initiative in Genomic Medicine
for the Americas (SIGMA)

AFRICA
Human Heredity and AUSTRALIA
Health in Africa (H3Africa) National Centere for
indigenous Genomics (NCIG)

Current Opinion in Biotechnology

Geographic scope of ongoing population-scale sequencing initiatives for Personalized Medicine (adapted from Ref. [45]).

the framework of an ethical and anonymous data proces-
sing, will have a significant impact in the design of
biomedical research activities. Blockchain-based crypto-
graphic techniques for patient anonymization using smart
contract technology [24] represent promising research
lines that still require substantial investigation. Moreover,
cloud computing is becoming a mainstream way to build
and deliver software and storage solutions (IBM Cloud,
Google Cloud, Amazon Web Services), by allowing sta-
keholders to use resources ‘on demand’ to foster repro-
ducibility [25], and promoting requirements to limit
security threats [26]. To be effective, biomedical data
must be secure but also Findable, Accessible, Interoper-
able, and Reusable (FAIR) [27]. Indeed, maintaining the
continuity of the main data sources, as in the case of the
ELIXIR Data Platform (www.elixir-europe.org/
platforms/data) [2], is crucial to prevent the seclusion
of data in silos.
Fundamental in this scenario is high performance com-
puting (HPC). Supercomputers and parallel processing
are essential for addressing complex problems with
intensive data tasks. European initiatives include the
big data ecosystem European Open Science Cloud
(EOSC, https://eosc-hub.eu/), and EuroHPC for exascale
supercomputers development [28]. These initiatives aim
to provide industry and public authorities with world-
class HPC solutions along with premier data storage,
management, and transport. In this regard, input/output
hardware innovations play a major role in fostering effec-
tive big data handling. An interesting example is IBM
POWER9/NVIDIA architecture specifically designed to
support artificial intelligence and deep learning [29].
Data analysis and interpretation
The key question in biomedical research is how to
extract knowledge from big data. Although some of the
hardest challenges for computing systems are focused
on extreme data analytics and data-intensive simula-
tions, such as streaming data analysis [30] and virtual
patient design [31], machine learning on high dimen-
sional data represents a prevalent concern. Biomedical
big data entail ensembles of complementary informa-
tion retrieved from heterogeneous sources, which can

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164 Systems biology

be referred to as multi-view data, representing multiple
facets of data instances in different feature spaces.
Multi-view data can be investigated thought several
data-driven integrative workflows that generally
require inference of associations among distinct enti-
ties [32].
Machine learning methods can be effectively applied to
deliver integrative solutions for multi-view data in
order to explain an event or predict an outcome. For
instance, generalized linear models (GLMs) [33] com-
ply with a broad model formulation where the outcome
is linearly related to factors and covariates through a
link function that permits the estimation of the model
parameters typically by maximum likelihood or Bayes-
ian techniques. As features of biological data often
exhibit some form of structure, such as groups of genes
with similar functions, structural regularization
methods such as Sparse Group LASSO (Least Absolute
Shrinkage and Selection Operator) is a common
approach for supervised multi-view feature selection.
Along with GLMs, common machine learning models
for multi-view data are Bayesian models such as the
naı̈ve Bayes classifier, ensemble-learning models such
as random forest, neural networks and more recently
deep learning (Figure 2).
Biomedical data pose unique challenges for deep learn-
ing [34], a repertoire of highly accurate and flexible
neural network-based machine learning techniques that
in the last few years have been successfully applied to
domain-specific applications. The rapid popularity of
deep learning resides in the convergence of novel
hardware improvements, easy-to-use software
packages, and the availability of large datasets fitting
vast parameter spaces.

Figure 2
E

PATIENT
QU
NI
CH
TE
AL
NT

BIOSAMPLE
ME
RI
PE
EX

REGRESSION CLUSTERING
Linear regression k-Means
Logistic regression Expectation-Maximization (EM)

REGULARIZATION INSTANCE-BASED METHODS DECISION TREES BAYESIAN METHODS

LASSO k-Nearest Neighbor (kNN) Decision Stump Naive Bayes
Elastic Net Self-Organizing Map (SOM) Conditional Decision Trees Bayesian Belief Networks (BBN)

ENSEMBLE METHODS NEURAL NETWORKS RULE-BASED METHODS DIMENSIONALITY REDUCTION

AdaBoost Deep Boltzmann Machine (DBM) Apriori algorithm Principal Component Analysis (PCA)
Random Forest Convolution Neural Network (CNN) Eclat algorithm Multidimensional Scaling (MDS)
Current Opinion in Biotechnology

Machine learning algorithms for multi-view data analysis. Biosamples from several experimental techniques (e.g. genomic, proteomic, and
metabolomic data) can be used to identify associations within and between multiple sets of patients, and generate integrative models for patient
stratification.

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 Big data analytics for personalized medicine Cirillo and Valencia 165

Table 2

Notable biomedical applications of Deep learning

Task Data type Method Reference

Transcription factor binding sites prediction PBM, SELEX, ChIP-seq and CLIP-seq CNN [46]
Promoter-enhancer interaction prediction Hi-C and genomic annotations CNN [47]
Metagenomic classification 16S rRNA sequences RNN [48]
Variant calling NGS data CNN [49]
Disease risk Gene variants CNN [50]
De novo drug design Chemical compounds RNN [51]
Hospitalization outcome prediction EHRs RNN [52]
Epileptic seizure prediction EEG RNN [53]
Medical images analysis Skin lesion images CNN [54]

CNN, convolutional neural network; RNN, recursive neural network; PBM, protein-binding microarrays; SELEX, systematic evolution of ligands by
exponential enrichment; ChIP, chromatin immunoprecipitation; CLIP, cross-linking immunoprecipitation; Hi-C, high-resolution chromosome
conformation capture; NGS, next generation sequencing; EEG, electroencephalogram.

Deep learning has largely been applied to biomedical
data integration and modeling (Table 2). In particular, it
has been effectively employed in the classification of
medical images and videos, often in combination with
processing of EHRs [35], and included in systems sup-
porting physician-computer interactions [36].
Massive volumes of aggregated biomedical data often
display different levels of granularity, that is, a variety of
data dimensionalities, sample sizes, sources and formats
[37]. In particular, small data sets, low numbers of samples,
and class imbalance, represent substantial problems typical
of many areas of biomedicine. A number of techniques,
such as data augmentation (e.g. generation of adversarial
examples) and transfer learning (e.g. repurposing features
of established models), are being explored to address these
problems [38]. As for the frequent lack of ground-truth or
expert-validated labels for training, novel machine learning
approaches such as weak supervision [39] are used to
automatically generate data labels to be used for deep
learning model training, for example annotating a corpus
of radiology reports to train an image classifier.
With a special emphasis on human decision making, a
series of new technologies inspired by neuroscience and
based on various forms of Natural Language Processing
(NLP) and computational linguistics, are referred to as
cognitive computing [40]. Compared to other approaches,
cognitive computing pursuits a dynamic process of obser-
vation, interpretation, evaluation, and decision. Limita-
tions relate to correct understanding of contextual mean-
ing and information uncertainty. The most popular
example of cognitive system is IBM Watson that has
been recently applied to several cancer types [41] and
neurological diseases [42]. Several reports inform on
technical details of Watson system [43], along with com-
ments discussing on its impact in the society [44].
potential to inspire systematic ways to process clinical and
molecular information that spans the four dimensions of
volume, velocity, variety, and veracity, referring to scale,
rate, forms, and content of generated data [7]. At present,
large amount of multi-omics, imaging, medical devices, and
EHR data are available from large-scale cohort and popula-
tion studies, revealing subtle differences in human genetics
and allowing Personalized Medicine interventions, while
engaging infrastructural and research management innova-
tion and sustainability. Challenges in big data analytics are
pointing to the development of effective applications in areas
where finding connections and insights can be difficult due to
data abundance and the complexity of biological systems.
Advanced machine learning methods such as deep learning
and platforms for cognitive computing represent the future
toolbox for the data-driven analysis of biomedical big data.
Encouraging progress in these areas will be indispensable for
future innovation in healthcare and Personalized Medicine.
Funding
This work was supported by BBVA Foundation
[“Precision Medicine from Big Data to Cognitive Com-
puting (ref. 76/2016)”])”], and the IBM-BSC Joint
Study Agreement (JSA) on Precision Medicine under
the IBM-BSC Deep Learning Center Agreement.
Conflict of interest statement
Nothing declared.
Acknowledgements
Authors would like to acknowledge Alba Jené and Salvador Capella for their
support and advice.
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