<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Archiving and Interchange DTD v1.0 20120330//EN" "JATS-archivearticle1.dtd">
<article xmlns:xlink="http://www.w3.org/1999/xlink">
  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>A Comparison between a Relational Database and a Graph Database in the context of a Personalized Cancer Treatment Application</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Alexandra Martinez</string-name>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Rodrigo Mora</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Daniel Alvarado</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Gustavo Lopez</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Steve Quiros</string-name>
          <email>steve.quirosg@ucr.ac.cr</email>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Centro de Investigacion en Enfermedades Tropicales, Facultad de Microbiolog a, Universidad de Costa Rica</institution>
          ,
          <addr-line>San Jose</addr-line>
          ,
          <country country="CR">Costa Rica</country>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>Centro de Investigaciones en Tecnolog as de la Informacion y Comunicacion, Universidad de Costa Rica</institution>
          ,
          <addr-line>San Jose</addr-line>
          ,
          <country country="CR">Costa Rica</country>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution>Escuela de Ciencias de la Computacion e Informatica, Universidad de Costa Rica</institution>
          ,
          <addr-line>San Jose</addr-line>
          ,
          <country country="CR">Costa Rica</country>
        </aff>
      </contrib-group>
      <abstract>
        <p>This paper presents a performance comparison between a relational database (implemented in MySQL) and a graph database (implemented in Neo4j). Unlike traditional benchmarks, this comparison is made in the context of a real health application which was developed in Costa Rica. The comparison encompassed twelve queries and three data size con gurations.The results of the comparison indicate that MySQL performs better than Neo4j in most cases, but has a poor performance when data size is large and the queries have multiple join operations.</p>
      </abstract>
      <kwd-group>
        <kwd>relational databases</kwd>
        <kwd>graph databases</kwd>
        <kwd>cancer treatment</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>-</title>
      <p>
        Information technology has been an enormous aid in the elds of medicine and
healthcare in general, as it facilitates the management and sharing of very large
amounts of data and its standardization. We have created a software
healthcare platform that supports the personalized cancer treatment process at
various stages. This software platform will be used by oncologists, pharmacists and
pathologists from the hospitals as well as by microbiologists and technicians
from the cancer lab. The actual personalized cancer treatment that is
implemented is the ATP Tumor Chemosensitivity Assay [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ], which will be o ered by
the university cancer lab to national public hospitals.
      </p>
      <p>When developing the software platform, we wondered which paradigm was
better suited for the task at hand: a traditional relational model or a modern
NoSQL model. As the literature review did not nd studies that were similar to
what we needed, we decided to build a exible enough platform that allows us
to change the underlying database transparently, so that we could experiment
with both types of database in order to decide which one worked best in our
context.</p>
      <p>The rest of the paper is organized as follows. Section 2 presents the
background on personalized cancer treatment and relevant database paradigms.
Section 3 describes the context. Section 4 speci es the methodology. Section 5 shows
the results and Section 6 states our conclusions.
2
2.1</p>
    </sec>
    <sec id="sec-2">
      <title>Background</title>
      <sec id="sec-2-1">
        <title>Personalized Cancer Treatment</title>
        <p>
          Cancer therapeutics are limited by the tumor's resistance to chemotherapy,
which is the major obstacle for e ective patient treatment [
          <xref ref-type="bibr" rid="ref4">4</xref>
          ]. In traditional
clinical practice, resistance is detected during treatment [
          <xref ref-type="bibr" rid="ref1">1</xref>
          ]. However, once a
tumor is resistant to a chemotherapy, it often becomes resistant to multiple
chemotherapeutic drugs. Hence, treating a cancer patient with a suboptimal
drug as a rst-line therapy lowers her chances of survival. Ideally, the rst-line
treatment should be the chemotherapeutic drug that has the maximum
probability of reducing tumor robustness.
        </p>
        <p>
          Early diagnosis of resistance is achieved by combining clinical, pathological
and molecular markers, and complementary in-vitro chemosensitivity tests.
Invitro chemosensitivity tests can predict which chemotherapeutic drug a patient
will bene t the most (or the least) from. One such in vitro test is the ATP Tumor
Chemosensitivity Assay (ATP-TCA) [
          <xref ref-type="bibr" rid="ref2">2</xref>
          ]. ATP-TCA has a predictive value of
93% for sensitivity (i.e., tumor's positive clinical response) and close to 100%
for resistance (i.e., tumor's clinical nonresponse). ATP-TCA has been reported
to increase tumor response rates and prolong survival times, and is particularly
useful when there are many alternative treatment protocols. It may be considered
the assay with best documented and validated technology [
          <xref ref-type="bibr" rid="ref2">2</xref>
          ].
        </p>
        <p>
          In brief, early diagnosis of resistance (including in-vitro chemosensitivity tests
like ATP-TCA) enables optimized and personalized cancer treatment [
          <xref ref-type="bibr" rid="ref4 ref5">4, 5</xref>
          ].
2.2
        </p>
      </sec>
      <sec id="sec-2-2">
        <title>Database Paradigms</title>
        <p>
          The Relational Paradigm The relational model, proposed by Edgar Codd
in 1970, has been the predominant paradigm. However, it is currently facing
strong competition from modern alternatives like object-relational and NoSQL
paradigms. The relational model represents data as a collection of relations, and
a relation is essentially a table of values where each row represents a set of related
values Column headers represent the attributes we want to store and every row
shares these attributes, but not their values. Relational databases work best
with structured data, which t easily into tables [
          <xref ref-type="bibr" rid="ref3">3</xref>
          ]. Formally, operations on
this model can be perfomed through relational algebra or relational calculus,
but the most popular query language is SQL (Structured Query Language), an
ANSI (American National Standards Institute) standard. Typically, database
applications use transactions to encapsulate a series of operations into a unit
of work Transactions have four main properties (known as ACID): Atomicity,
Consistency, Isolation and Durability, which together guarantee the reliability
of a relational database [
          <xref ref-type="bibr" rid="ref8">8</xref>
          ].
        </p>
        <p>The Graph Paradigm Graph oriented database management systems are
designed to facilitate relationships between the nodes. Instead of using foreign
keys to represent a relationship, graph databases use arcs that directly connect
two nodes. Operations on this model can be performed through a graph query
language.</p>
        <p>
          Graph databases are one of the four categories of NoSQL databases. The
other categories of NoSQL databases are: key-value, documents and column
oriented. NoSQL database management systems emerged as a response to the
limitations of the relational technology and the demands of the Web 2.0 age. They
were born with the advent of MapReduce and BigTable in 2004 and 2006,
respectively [
          <xref ref-type="bibr" rid="ref7">7</xref>
          ]. The NoSQL movement has since grown rapidly, to the point that today
there are more than 225 NoSQL storage systems (according to
http://nosqldatabase.org, retrieved on February 24th, 2016). The term \NoSQL" (which
the community has interpreted as not only SQL) denotes the next generation of
database management systems, that are mostly non-relational, distributed, open
source and horizontally scalable. Additionally, they are often schema-free,
support easy replication, have a simple API, are eventually consistent (BASE instead
of ACID) and can handle huge amount sof data. NoSQL database management
systems generally process data quicker than relational ones, partly because of
their simpler data models and because they don't have to commit to certain
restrictions imposed by the ACID properties [
          <xref ref-type="bibr" rid="ref3">3</xref>
          ].
        </p>
        <p>
          NoSQL paradigm may never completely replace relational paradigm, but it
might become a better option for projects that work with unstructured data and
require scalability [
          <xref ref-type="bibr" rid="ref3">3</xref>
          ].
3
        </p>
      </sec>
    </sec>
    <sec id="sec-3">
      <title>Context</title>
      <p>
        The databases used in this comparison were developed as a part of a software
platform that supports personalized cancer therapy based on the ATP-TCA
assay. The purpose of this platform is to facilitate the collection, storage,
management, and communication of ATP-TCA assays data. A detailed description
of the design of this platform was described in [
        <xref ref-type="bibr" rid="ref6">6</xref>
        ]. All the queries used in the
comparison correspond to real operation requirements of the platform, although
not all of them are currently accesible from the web application.
      </p>
      <p>The architecture of this platform consisted of three layers: a front-end, a
backend, and a web services layer that allows communication between the other two.
The front-end was a web application developed with Microsoft .NET. The
backend consisted of either a relational database that was implemented in MySQL,
or a graph database that was implemented in Neo4J. Web services were used to
allow for transparent switching of back-end implementation . Given that
medical information of patients is considered sensitive data, we implemented access
control through the well established and accepted ASP.NET security,
authentication and authorization framework. Access control was built within the front-end
application since the server that runs it is the only one that can be publicly
accessed; all other servers are con gured in a private and protected network.
4</p>
    </sec>
    <sec id="sec-4">
      <title>Methodology</title>
      <p>An experiment was designed to compare the performance of the relational and
graph databases. The performance metric used was the mean response time of
each database engine to a speci c set of queries. The same set of queries was
executed against each database engine (MySQL and Neo4j). To make sure that
the queries performed on both engines were equivalent, for each pair we compared
and veri ed that the returned result was the same. (We needed to do this since
the formulation and syntax of the same query was drastically di erent in each
database).
4.1</p>
      <sec id="sec-4-1">
        <title>Experimental con guration</title>
        <p>We used virtual machines mounted on a virtualization server with eight 2.93
GHz Intel Xeon processors, 32GB of RAM memory and 8TB of secondary
storage. This virtualization server ran an ESXi-5.5.0-1331820-standard. Each of the
virtualized machines used Debian 7 (wheezy). We used version 14.14 Distrib
5.5.38 of MySQL for Debian and version 1.8.1 of Neo4J.</p>
        <p>When installing and con guring the Neo4j and MySQL database
management systems (each on one server), we followed the instructions published in
their respective websites, to avoid favoring one of them with special tunings.
After these servers (virtual machines) were con gured, we cloned them,
following the instructions provided by VMware ESXi. A clean version of each virtual
machine was stored before loading the data. We did not consider di erent
alternatives of indexes, blocking schemes or hashing structures; instead we used the
default ones that come with each database management system.</p>
        <p>The experiments were performed using three di erent datasets of
increasing size: the rst dataset had 1.000 entries per table or node type, the second
dataset had 10.000 entries per table or node type, and the third dataset had
100.000 entries per table or node type. Each dataset was generated with
generatedata.com, a free and open source tool created by Benjamin Keen. All data
was randomly generated, except for the primary keys and the foreign keys
(referenced attributes in the graph database), which were generated in ascending
order so that data could be related in a coherent and automated way. Automatic
refencing of primary keys (attributes in nodes) from foreign keys was possible
through a script written by us.</p>
        <p>The deployed database servers were not optimized for their virtual machine's
RAM size or other characteristics. All the virtual machines had the same
characteristics: 2048 MB of RAM, 32-bit operating systems, 30.93 MB of memory
overhead, 16.11 GB of provisioned storage, and one processor (2.93 GHz Intel
Xeon processor). To assure the estability of the virtualization server while
running the tests, only one virtual machine was running at a time. Moreover, the
virtual machines hosting the database servers did not have internet connection,
and a direct ethernet connection was used to send the quieries and gather the
results.</p>
        <p>We chose JMeter as the tool for executing the tests. This tool allowed us
to establish similar execution parameters for the two databases (for example,
ushing the database cache before each query). We con gured it to execute ve
threads, each running a loop of 50 calls, which resulted in 250 executions of each
query.
4.2</p>
      </sec>
      <sec id="sec-4-2">
        <title>MySQL Database</title>
        <p>The relational data schema had 28 tables (relations) in total. The conceptual
schema of the implemented database is shown in Fig. 1. No index was added
to the basic implementation of this database schema, because we intended to
evaluate its performance while trying to avoid any bias due to its design or
implementation.
4.3</p>
      </sec>
      <sec id="sec-4-3">
        <title>Neo4j Database</title>
        <p>The graph database had 22 node types and 23 relationship types. We talk about
node types and relationship types due to the data organization nature, where
there is no prede ned schema equivalent to relational tables. Each node may
have di erent characteristics without having to comply with established rules
or design restrictions. Also, each relationship instance depends directly on the
nodes it connects. The logical schema of the database implemented is shown in
Fig. 2. Likewise, no index was added to the basic implementation of this database
schema.
4.4</p>
      </sec>
      <sec id="sec-4-4">
        <title>Queries</title>
        <p>The system was evaluated using twelve queries, which are described next. In
MySQL, the queries were implemented with SQL while in Neo4j, the queries
were implemented with Cypher (a declarative graph query language, inspired on
SQL).</p>
        <p>Query 1 Returns the doctors who have participated in a patient's treatment. In
SQL, this query includes two join operations over three tables (see code below),
while in Cypher, it uses three node types and two relationship types.
SELECT p . Name , p . Id , d . Name , d . I d
FROM D o c t o r d INNER JOIN FollowUp f ON f . D o c t o r I d = d . I d</p>
        <p>INNER JOIN P a t i e n t p ON p . I d = f . P a t i e n t I d
WHERE p . Name = ' Gwendolyn '</p>
      </sec>
      <sec id="sec-4-5">
        <title>ORDER BY p . I d</title>
        <p>Fig. 1. Conceptual schema of the relational database.</p>
        <p>Fig. 2. Logical schema of the graph database.</p>
        <p>Query 2 Returns the name, date and result of all medical exams a patient has
undergone. In SQL, this query includes just one table (see code below), while in
Cypher, it uses two relationship types.</p>
        <sec id="sec-4-5-1">
          <title>SELECT Name , Date , R e s u l t s FROM C o n s i s t s O f WHERE P a t i e n t I d = 200001094</title>
        </sec>
      </sec>
      <sec id="sec-4-6">
        <title>ORDER BY Date DESC</title>
        <p>Query 3 Retrieves the number of samples for each tumor type. In SQL, this
query includes one join operation between two tables (see code below), whereas
in the graph schema it includes one relationship type.</p>
      </sec>
      <sec id="sec-4-7">
        <title>SELECT Name , count ( )</title>
        <p>FROM Sample s INNER JOIN TumorType t ON t . Id = s . Id</p>
      </sec>
      <sec id="sec-4-8">
        <title>GROUP BY Name</title>
      </sec>
      <sec id="sec-4-9">
        <title>ORDER BY Name</title>
        <p>Query 4 Returns the average, minimum and maximum age across all patients.
The SQL code for this query is:
SELECT avg (TIMESTAMPDIFF(YEAR, BirthDate , CURDATE( ) ) ) ,
min(TIMESTAMPDIFF(YEAR, BirthDate , CURDATE( ) ) ) ,
max(TIMESTAMPDIFF(YEAR, BirthDate , CURDATE( ) ) )
FROM P a t i e n t
Query 5 Retrieves the percentage of inadequate samples. The SQL code is:
SELECT ( ( s e l e c t count ( ) FROM Sample WHERE s u i t a b l e = 0 )
/ ( s e l e c t count ( ) FROM Sample ) )
from Sample LIMIT 1
Query 6 Obtains the average, minimum and maximum values for each index
(like IC90, IC50, AUC, etc.) across all chemosensitivity assays. In SQL, this
query includes one join operation between two tables (see code below), whereas
in Cyhper it includes one relationship type.</p>
      </sec>
      <sec id="sec-4-10">
        <title>SELECT nombre , avg ( Value ) , min( Value ) , max( Value )</title>
        <p>FROM FormedBy INNER JOIN Index on Id = I n d e x I d</p>
      </sec>
      <sec id="sec-4-11">
        <title>GROUP BY Name ORDER BY Name</title>
        <p>Query 7 Retrieves a patient's information based on her ID. In SQL, this query
involves just one table (see code below), and in Cypher, it involves one node
type.</p>
      </sec>
      <sec id="sec-4-12">
        <title>SELECT FROM P a t i e n t</title>
        <p>WHERE Id = ' 200001002 '
Query 8 Retrieves a patient's information based on her name. In SQL, this query
involves a single table (see code below), while in Cypher, it involves one node
type.</p>
      </sec>
      <sec id="sec-4-13">
        <title>SELECT FROM P a t i e n t</title>
        <p>WHERE Name = ' Gwendolyn '
Query 9 Returns the pathology and cytometry markers obtained for each female
patient. In SQL, this query involves three join operations over four tables (see
code below), while in Cypher, it involves ve relationship types.</p>
        <sec id="sec-4-13-1">
          <title>SELECT p . Id , m. Name , d . Name</title>
          <p>FROM P a t i e n t p JOIN D e t e c t s d ON p . Id = d . P a t i e n t I d JOIN
Measures m ON p . Id = m. P a t i e n t I d JOIN Cytometry c ON m
. Date = c . Date AND m. SampleId = c . SampleId
WHERE p . Sex = true AND c . V a l i d a t e d = true</p>
        </sec>
      </sec>
      <sec id="sec-4-14">
        <title>ORDER BY p . Id</title>
        <p>Query 10 Retrieves the drugs (and the companies that produces them) used in
each chemosensitivy assay. In SQL, this query involves three join operations over
four tables (see code below), while in Cypher, it involves four relationship types.</p>
        <sec id="sec-4-14-1">
          <title>SELECT DISTINCT c . DateTime , d . Name , y . Name</title>
          <p>FROM Drug d JOIN I n c l u d e s t ON d . Id = t . DrugId
JOIN IsComposedOf c ON c . t . TreatmentId = t . TreatmentId</p>
          <p>JOIN Company y ON d . Id = y . IdDrug
ORDER BY c . DateTime
Query 11 Retrieves all adequate samples. In SQL, this query involves just one
table (see code below), while in Cypher, it involves one node type.</p>
        </sec>
      </sec>
      <sec id="sec-4-15">
        <title>SELECT FROM Sample</title>
        <p>WHERE S u i t a b l e &lt;&gt; 0
Query 12 Retrieves all samples of a patient, based on her ID. In SQL, this
query involves just one table (see code below), and in Cypher, it involves one
node type.</p>
      </sec>
      <sec id="sec-4-16">
        <title>SELECT FROM Sample</title>
        <p>WHERE P a t i e n t I d = 200001053
5</p>
      </sec>
    </sec>
    <sec id="sec-5">
      <title>Results</title>
      <p>Next we present the results obtained from our experiment. Fig. 3 shows the
mean response time in miliseconds (ms) of MySQL and Neo4J for each of the
12 queries, under the three datasets used. From Fig. 3 we observe that, for most
queries, MySQL performs better than Neo4j (green lines are below orange lines
most of the time). Furthermore, for some queries Neo4j shows worse performance
than MySQL even when comparing di erent data sizes: 1k for Neo4j and 100k for
MySQL (i.e., MySQL sometimes outperforms Neo4j even if the size of the data is
3 orders of magnitude larger). However, for query 9, the performance of MySQL
is much worse than Neo4j at 100k data size (surpassing Neo4j by more than 2
orders of magnitude). Query 9 is probably the most complex query in terms of
data that needs to be related (join operations in the relational model), since it
requires three joins over four tables plus an ordering operation (order by clause),
so it seems data size takes a toll on performance when queries are complex. It
is well known that joins are costly operations in relational databases, hence we
expect to see a performance degradation as data (table) size increases in the
presence of multiple joins. Likewise, for query 10 the performance of MySQL
is worse than Neo4j at 100k data size, and this query also has 3 joins plus an
ordering operation.
6</p>
    </sec>
    <sec id="sec-6">
      <title>Conclusion</title>
      <p>We compared the performance of a relational database (implemented in MySQL)
and a graph database (implemented in Neo4j), in the context of a health
application for personalized cancer treatment in Costa Rica. A detailed description of
the methodology was o ered, including the experimental setup. The comparison
encompassed twelve queries and three data size con gurations: all tables or node
types with 1.000 entries, 10.000 entries and 100.000 entries. The results of the
experiment indicate that MySQL performs better than Neo4j in most cases, but
Neo4j outperforms MySQL in two queries that require multiple join operations
when data size is 100.000 entries per table or node type.
This work was partially supported by Research Center for Communication and
Information Technologies (CITIC) and by Computer Science and Information
Department (ECCI), at the University of Costa Rica.</p>
    </sec>
  </body>
  <back>
    <ref-list>
      <ref id="ref1">
        <mixed-citation>
          1.
          <string-name>
            <surname>Kitano</surname>
          </string-name>
          , H.:
          <article-title>Cancer as a robust system: implications for anticancer therapy</article-title>
          .
          <source>Nat Rev Cancer</source>
          <volume>4</volume>
          (
          <issue>3</issue>
          ),
          <volume>227</volume>
          {
          <volume>235</volume>
          (03
          <year>2004</year>
          )
        </mixed-citation>
      </ref>
      <ref id="ref2">
        <mixed-citation>
          2.
          <string-name>
            <surname>Kurbacher</surname>
            ,
            <given-names>C.M.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Cree</surname>
            ,
            <given-names>I.A.</given-names>
          </string-name>
          :
          <article-title>Chemosensitivity testing using microplate adenosine triphosphate-based luminescence measurements</article-title>
          .
          <source>Methods Mol Med 110</source>
          ,
          <issue>101</issue>
          {
          <fpage>120</fpage>
          (
          <year>2005</year>
          )
        </mixed-citation>
      </ref>
      <ref id="ref3">
        <mixed-citation>
          3.
          <string-name>
            <surname>Leavitt</surname>
          </string-name>
          , N.:
          <article-title>Will nosql databases live up to their promise? In: Computer</article-title>
          . vol.
          <volume>43</volume>
          , p.
          <fpage>1214</fpage>
          . IEEE Computer Society (
          <year>2010</year>
          )
        </mixed-citation>
      </ref>
      <ref id="ref4">
        <mixed-citation>
          4.
          <string-name>
            <surname>Lippert</surname>
            ,
            <given-names>T.H.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Ruo</surname>
            ,
            <given-names>H.J.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Volm</surname>
            ,
            <given-names>M.</given-names>
          </string-name>
          :
          <article-title>Intrinsic and acquired drug resistance in malignant tumors. the main reason for therapeutic failure</article-title>
          .
          <source>Arzneimittelforschung</source>
          <volume>58</volume>
          (
          <issue>6</issue>
          ),
          <volume>261</volume>
          {
          <fpage>264</fpage>
          (
          <year>2008</year>
          )
        </mixed-citation>
      </ref>
      <ref id="ref5">
        <mixed-citation>
          5.
          <string-name>
            <surname>Lippert</surname>
            ,
            <given-names>T.H.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Ruo</surname>
            ,
            <given-names>H.J.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Volm</surname>
            ,
            <given-names>M.</given-names>
          </string-name>
          :
          <article-title>Intrinsic and acquired drug resistance in malignant tumors. the main reason for therapeutic failure</article-title>
          .
          <source>Arzneimittelforschung</source>
          <volume>58</volume>
          (
          <issue>6</issue>
          ),
          <volume>261</volume>
          {
          <fpage>264</fpage>
          (
          <year>2008</year>
          )
        </mixed-citation>
      </ref>
      <ref id="ref6">
        <mixed-citation>
          6.
          <string-name>
            <surname>Martinez</surname>
            ,
            <given-names>A.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Mora</surname>
            ,
            <given-names>R.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Lpez</surname>
            ,
            <given-names>G.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Bolaos</surname>
            ,
            <given-names>C.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Alvarado</surname>
            ,
            <given-names>D.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Solano</surname>
            ,
            <given-names>A.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Lpez</surname>
            ,
            <given-names>M.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Quirs</surname>
            ,
            <given-names>S.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Bez</surname>
            ,
            <given-names>A.</given-names>
          </string-name>
          :
          <article-title>New Advances in Information Systems and Technologies, chap. Design and Evaluation of a Personalized Cancer Treatment System using HumanComputer Interaction Techniques</article-title>
          . Springer International Publishing (
          <year>2016</year>
          )
        </mixed-citation>
      </ref>
      <ref id="ref7">
        <mixed-citation>
          7.
          <string-name>
            <surname>Vicknair</surname>
            ,
            <given-names>C.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Macias</surname>
            ,
            <given-names>M.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Zhao</surname>
            ,
            <given-names>Z.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Nan</surname>
            ,
            <given-names>X.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Chen</surname>
            ,
            <given-names>Y.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Wilkins</surname>
            ,
            <given-names>D.</given-names>
          </string-name>
          :
          <article-title>Database research: Are we at a crossroad? re ection on nosql</article-title>
          .
          <source>In: Proceedings of the 48th Annual Southeast Regional Conference. ACM</source>
          (
          <year>2010</year>
          )
        </mixed-citation>
      </ref>
      <ref id="ref8">
        <mixed-citation>
          8.
          <string-name>
            <surname>Vicknair</surname>
            ,
            <given-names>C.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Macias</surname>
            ,
            <given-names>M.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Zhao</surname>
            ,
            <given-names>Z.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Nan</surname>
            ,
            <given-names>X.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Chen</surname>
            ,
            <given-names>Y.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Wilkins</surname>
            ,
            <given-names>D.:</given-names>
          </string-name>
          <article-title>A comparison of a graph database and a relational database</article-title>
          .
          <source>In: Proceedings of the 15th International Conference on Network-Based Information Systems</source>
          . IEEE (
          <year>2012</year>
          )
        </mixed-citation>
      </ref>
    </ref-list>
  </back>
</article>