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  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>Security-oriented Portals for the Life Sciences</article-title>
      </title-group>
      <contrib-group>
        <aff id="aff0">
          <label>0</label>
          <institution>R.O. Sinnott</institution>
          ,
          <addr-line>T. Doherty, J. Jiang, S. McCafferty</addr-line>
          ,
          <institution>A. Stell, J. Watt National e-Science Centre University of Glasgow Glasgow G12 8QQ</institution>
        </aff>
      </contrib-group>
      <abstract>
        <p>Motivation: The life sciences are broad in scope and cover multiand inter-disciplinary domains as well as the biological domain. These domains can for example involve researchers from the clinical, social, geo-spatial and computer sciences amongst others, e.g. in understanding genetic variations across a population as might be undertaken through a genome-wide association study. Given, this it is essential that portals for these communities are targeted to the individual expertise of the particular domain scientists. Thus tools available to a bioinformatician through a portal might well be meaningless to a social scientist and vice versa. Furthermore certain domains demand that fine-grained access control on data is supported. In this paper we outline how a portfolio of life science related projects at the National e-Science Centre (NeSC) at the University of Glasgow have benefited from security-oriented portals focused upon ease of access, configuration and usage, where data providers are assumed to be autonomous and able to make their own local finegrained access control decisions. We describe the basic technologies that underlie these solutions and outline specific case studies in their application in the areas of depression, self-harm and suicide, and in the area of paediatric endocrinology focusing in particular on rare diseases associated with sex development.</p>
      </abstract>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>1 INTRODUCTION</title>
      <p>The life sciences have much to benefit from the application
of e-Science and Grid based technologies: seamless access
to large scale high performance computing (HPC) facilities;
technologies and processes that help in coping with the
explosion of data sets in high throughput post-genomic life
sciences, and supporting multi- and inter-disciplinary
research communities in tackling major research questions are
some of the most obvious ones. Despite this, the impact
envisaged in the application of e-Science and Grids in the
life sciences domain has not been as major as first hoped
for. There are a variety of reasons for this. These include:
• the complexity of the middleware that is used;
• the lack of clear understanding and expression of life
science research community requirements;
• a moving set of life science research questions;
*To whom correspondence should be addressed.
• a moving set of scientific data and understanding of
that data;
• a perceived lack of security of Grids and issues this has
on data access and release.</p>
      <p>
        This list is not complete and there are doubtless other issues
that could be brought to bear on life science community
take-up. Some of these are described in more detail in [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ]. In
this paper we argue that many these issues can now be
tackled. In particular we focus upon solutions that tackle several
major uptake considerations: usability of the
eInfrastructures that are developed; support for
interdisciplinary research and security considerations for all
protagonists involved in life science research. We claim that
this is now possible through security-oriented portals
targeted to the specific needs of life science researchers. This
is demonstrated through two case studies in the area of
public health and genetics of rare diseases.
      </p>
      <p>The rest of this paper is structured as follows. Section 2
describes portal based technologies and how they have been
applied at the National e-Science Centre (NeSC) at the
University of Glasgow (www.nesc.gla.ac.uk). Section 3 describes
technology support for secure access to and configuration of
portals. Section 4 describes the application of these
solutions to particular case studies. Finally we draw some
conclusions on the work as a whole and outline areas of future
development.</p>
    </sec>
    <sec id="sec-2">
      <title>2 GRID PORTALS</title>
      <p>Web portals provide a single point of access where a variety
of information is aggregated and personalised to individuals
to improve their experience in accessing and using a range
of Internet resources. Common features of web portals
include support for categorization of web content and
advanced search facilities. Grid portals build upon the general
web portal model to deliver the benefits of Grid computing
to virtual communities of users, providing a single access
point to Grid services and resources. Web 2.0 based
solutions whether this be wikis, social networking capabilities,
lightweight tools, e.g. for visualisation or mash-ups, can
also be made available through portals.</p>
      <p>The major difference between a Web portal and a Grid
portal is that Grid portals provide a single point of access for
Grid resources specific to a given domain, rather than more
general Internet-based web pages or content. Grid portals
provide end users with a customized view of software and
hardware resources specific to their particular problem
domain. This customization can be based upon the privileges
that end users have. This can be used to restrict or authorize
access to collections of remote services and data sets. Grid
portals should ideally allow researchers to focus on their
research problems by making the Grid a transparent
extension of their desktop computing environment.</p>
      <p>The development of targeted portals for the life sciences
in the large, i.e. without focusing on particular
specializations, offers a direct way in which a rich variety of
applications and resources can be made available in a transparent
manner to users who do not wish to become Grid experts.
Given the depth and range of life science research currently
being pursued, it is highly that a single one-stop shop portal
could be established for all researchers.</p>
      <p>That said, Grid-based life science portal solutions should
meet the following set of requirements:
• Usability – the portal should be developed with both the
experienced and inexperienced research communities in
mind. This might benefit from use of backend servers to
manage user certificates and Grid credentials required
across the life science resources.
• Single sign-on – in addition to secure access to a
Gridbased life science portal itself, seamless access to a
range of life science resources without the need for
multiple authentications should be supported. Access
should, of course, depend on user privileges. The
concept of single sign-on is one of the characterizing
features of the Grid
• Interoperability – it should be possible for research
communities to develop their own services using
potentially different middleware on their own local resources,
but be able to make these available to remote researchers
through portal technologies.
• Support for research – it is essential that the services
and data sets made available through the portals meet
the real needs of life science researchers. Their input and
feedback should drive the design and development of
these portals and their content.
• Support for collaboration – Grid-based life science
portals should facilitate collaboration between researchers
at all levels – within an institution, between institutions,
across national and international levels.
• Portal administration and management – user
communities should be able to establish and ultimately manage
their own services and their own user base. The shared
resources underlying these communities need to be
autonomous, however, and under the control of these
communities.
• Monitoring – administrators and users should have
direct access to monitoring information about various
aspects of the Grid for their virtual organization, for their
institution, and for those using the shared resources.
This might include notifications of new data sets or new
tools of interest to life science communities.
• Security – certain life science communities and data
providers demand fine-grained security for tailoring
access and usage of Grid resources. This might be based
on specific roles particular to a virtual organization.
Whilst it is possible to develop hand-crafted portals, recent
advances in this area have resulted in Grid portal
frameworks which facilitate re-use of code and support various
forms of structuring portal pages. Grid portal frameworks
provide a set of basic functionalities and infrastructure for
developing further portal components as plug-ins. Common
components are offered for security (e.g. access
management), for personalisation (e.g. user/group profiles), and for
different presentation capabilities (e.g. JSP, XSP,
XML/XSLT).</p>
      <p>Portals themselves provide access to families of portlets
or other hosted applications. Portlets are typically
Javabased web components managed by a portlet container that
processes requests and generates dynamic content. Portals
use portlets as pluggable user interface components,
providing a presentation or access layer to systems. Portlets
support modular and user centric web applications. Portlets are
the building blocks of portals and are typically small units
of functionality within a portal. Each portlet typically
provides an interface to a Grid service offering some well
defined functionality. Users and administrators of
communities or virtual organisations more generally can build
customized environments by adding portlets.</p>
      <p>As we shall see in section 3, for advanced scenarios,
security techniques can be used to authorize use of particular
portlets or the resources available to the services accessible
via those portlets.</p>
      <p>It is worth noting that to support portlet and portal
interoperability, the portal community and wider industry have
developed two key standards of relevance to the Grid
community: the Java Portlet Specification (JSR-168) and the
Web Service for Remote Portlets (WSRP). JSR-168 enables
interoperability among portlets and portals. The
specification defines the contract between a portlet and portlet
container, and a set of portlet APIs that address personalization,
presentation, and security. The specification also defines
how to package portlets in portal applications. WSRP allows
plug-and-play of content sources (portlets) within portals
and other aggregating web applications. WSRP standardizes
the consumption of web services in portal front-ends, and
the way in which content providers write web services for
portals. This allows content producers to maintain control
over the code that formats the presentation of their content.
By reducing the cost for aggregators to access their content,
WSRP improves the integration of content sources into
pages for end users.</p>
      <p>WSRP and JSR-168 are complementary specifications.
JSR-168 defines a standard portlet API for Java-based
portals. WSRP allows content to be hosted in the environment
most suitable for its execution, while still being easily
accessed by content aggregators. Second generation Grid
portals can be produced from pluggable (JSR-168 compliant)
Grid portlets. Running inside a portlet container, portlets
can be added or removed, thus providing administrators
with the ability to customize access and usage of Grid
services at portal level. A portal built from Grid portlets can
provide users with the ability to integrate services provided
by different Grid-enabling technologies. This aspect is
critical to the success of life sciences since a range of distributed
services will likely be developed by different communities
and institutions, and subsequently made accessible through
common research specific portals (VREs).</p>
      <p>The NeSC at Glasgow have developed a large portfolio of
JSR-168 compliant portlets that are available in numerous
portals supporting various life science research
communities. Furthermore, through the Open Middleware
Infrastructure Institute (OMII-UK) Security Portlets project
(SPAMGP) at NeSC Glasgow
(www.nesc.gla.ac.uk/projects/omiisp) we have also developed a collection of JSR-168
compliant security-oriented portlets that support simple,
userdriven portal security based upon information provided by
the Internet2 Shibboleth technology
(http://shibboleth.internet2.edu) and the UK Access
Management Federation (www.ukfederation.org.uk).
3</p>
    </sec>
    <sec id="sec-3">
      <title>SECURITY INFRASTRUCTURES</title>
      <p>
        As mentioned many communities are dissuaded from
accessing and using Grid resources due to the complexity of
the middleware and associated processes. Much of this
stems from the demands to acquire and use X.509 based
certificates as used to support the public key infrastructure
(PKI) allowing single-sign on to distributed Grid resources.
The issues with PKIs including their limitations are
discussed in [
        <xref ref-type="bibr" rid="ref2 ref3 ref4">2-4</xref>
        ]. To overcome this, the UK and many
international communities are moving to federated access control
based upon the Internet2 Shibboleth technologies.
      </p>
      <p>When a user attempts to access a Shibboleth protected
service or Service Provider (SP) more generally, they are
typically redirected to a WAYF server that exists as part of
the federation that asks the user to pick their home Identity
Provider (IdP) from a list of known and trusted sites. The
service provider site already has a pre-established trust
relationship with each home site, and trusts the home site to
authenticate its users properly.</p>
      <p>After the user has picked their home site, their browser is
redirected to their site’s authentication server, e.g. an LDAP
repository, and the user is invited to log in. After successful
authentication, the home site redirects the user back to the
SP and the message carries a digitally signed Security
Assertion Markup Language (SAML) authentication assertion
message from the home site, asserting that the user has been
successfully authenticated (or not!) by a particular means.
The actual authentication mechanism used is specific to the
IdP.</p>
      <p>If the digital signature on the SAML authentication
assertion is verified and the user has successfully authenticated
themselves at their home site, then the SP has a trusted
message providing it with a temporary pseudonym for the user
(the handle), the location of the attribute authority at the IdP
site and the service provider URL that the user was
previously trying to access. The resource site then returns the
handle to the IdP’s attribute authority in a SAML attribute
query message and is returned a signed SAML attribute
assertion message. The Shibboleth trust model is that the
target site trusts the IdP to manage each user’s attributes
correctly, in whatever way it wishes. So the returned SAML
attribute assertion message, digitally signed by the origin,
provides proof to the target that the authenticated user does
have these attributes.</p>
      <p>The attributes used in this assertion may then be used to
authorise the user to access particular areas of the resource
site. Once authenticated through Shibboleth, the notion of
single sign-on is supported whereby a user may redirect
their browser to other protected Shibboleth resources with
no need for re-authentication.</p>
      <p>Underlying Shibboleth-based SAML token exchanges are
a core set of attributes based upon the eduPerson object
class (www.educause.edu/eduperson/) that are pre-agreed
across the federation so that an SP can make its own local
access control decision. It is essential that interoperability
exists between attribute authorities issuing attribute
assertions, policy writers defining access policies, and access
decision functions that make decisions based on the
initiator’s attributes and sites target and resource policy.</p>
      <p>However given the fact that Grids can be used to establish
e-Infrastructures and more security-oriented VOs, the
requirement to have VO specific attributes defined and
embedded in core eduPerson attributes are highly desirable.
The most likely attribute for this purpose is the
eduPersonEntitlement attribute. The eduPersonEntitlement
attribute can utilise structured XML data representative of large
scale Grid infrastructure users and IdPs. This might include
the VO they are involved in, the roles that they might have
in that VO etc.</p>
      <p>The SPAM-GP exploits Shibboleth-based access to Grid
portals and provides tooling that allows usage of Shibboleth
information, including VO-specific attributes to be utilized.
In particular SPAM-GP developed a family of JSR-168
portlets that support:
• scoped attribute management (SCAMP) which allows
restricted and syntactically correct manipulation of
the Shibboleth attribute acceptance policy,
streamlining the subset of IdPs from whom a portal will accept
user attributes across the federation.
• creation and usage of X509 attribute certificates
(ACP) to allow distributed service providers to make
their own local authorisation decisions when users
attempt to invoke remote (protected) services;
• content configuration allowing dynamic configuration
of portal content based on Shibboleth attributes and
knowledge of available services. Once authenticated
to a portal via Shibboleth, users are presented with a
filtered view of available portlets (and hence access to
a restricted set of services). This portlet has been
targeted specifically to extend the GridSphere portal
framework.</p>
      <p>
        The detailed implementation of these portlets and the
infrastructure that is required to support them is described in
detail in [
        <xref ref-type="bibr" rid="ref5">5</xref>
        ]. Our focus here is to show how these portlets
support life science researchers. We demonstrate this in the
ESRC funded DAMES project and the EU FW7 EuroDSD
projects.
4
      </p>
    </sec>
    <sec id="sec-4">
      <title>CASE STUDIES</title>
      <sec id="sec-4-1">
        <title>4.1 DAMES</title>
        <p>The social sciences as with many other domains are awash
with data. The ESRC funded DAMES project is developing
systems that will help in tackling the problems facing this
community. The DAMES project as a whole has a variety of
themes. These include occupational data management; ethic
and minority data management; educational data
management and the one of concern here: e-Health data
management. The project is exploring the data management
challenges associated with access to a wide range of data sets
cross multiple e-Health related disciplines. These include
clinical data sets such as the Scottish Morbidity Records
(SMR) covering hospital admissions, mental health and
psychosis, cancer and birth and death related data sets; Census
related data sets and geospatial data sets.</p>
        <p>Scotland is especially well placed to support e-Health
related research. Clinical information has been captured and
curated for over 30 years in Scotland and an extensive
record of the health of the Scottish population exists. The
DAMES project has focused in particular upon data sets
associated with mental health and is exploring the issues
related to depression, self-harm and suicide. In particular it
is attempting to answer questions related to the factors that
can impact upon individuals suffering from some form of
mental health problem. Thus what is the impact of living
alone on suicide rates? What is the impact on suicide rates
on access to prescription drugs? What is the impact on
suicide rates on access to park land? There are in short a
multitude of research questions that could potentially be
answered if the appropriate data resources could be integrated
and analysed.</p>
        <p>To support these kinds of scenarios the various data sets
have been acquired and made available through a targeted
DAMES portal. Ideally the data sets themselves would
remain at the remote data provider sites however in the first
instance we have been given direct access to randomized
copies of the associated clinical data sets. This was made
possible through the previous MRC funded Virtual
Organisations for Trials and Epidemiological Studies (VOTES –
www.nesc.ac.uk/hub/projects/votes) project. The data sets
are identical in structure to the actual SMR data sets, i.e.
they have the same schema. However the data itself has
been pseudo-anonymised to remove patient identifying
information. Nevertheless much of this information can be
used directly for building proof of concept systems.</p>
        <p>To begin with a family of portlets has been developed
that offers user interfaces to targeted data services. For
simplicity, we associate a particular portlet with a given role as
returned by the Shibboleth IdP. Using the content
configuration portlet from SPAM-GP it is possible to associate
possession of roles with associated portlets. It is of course
feasible to extend this so that possession of a given role can be
used to give access to a family of portlets and associated set
of group permissions inside of the portal framework.</p>
        <p>Originally the DAMES work was based upon the
GridSphere technologies (www.gridsphere.org), however
more recently we have targeted the LifeRay portal
environment (www.liferay.com). This was primarily due to the lack
of continued support for the GridSphere framework.</p>
        <p>The portlets themselves allow targeted access to a subset
of variables available in the particular data sets themselves.
Thus in the case of the mental health related scenarios, these
include Census variables associated with general health of
the population; SMR variables associated with mental health
including subsets of SMR01 (hospital admissions data);
SMR04 (mental health and psychosis data) and SMR99
(death related variables where the cause of death was
indicated as suicide).</p>
        <p>To prove the conceptual approach of secure portlet based
access to distributed data sets, we developed multiple
different portlets for each data set and associated these with
particular roles. In particular we identified advanced and basic
roles. Thus to see the advanced portlets for SMR04 a user
would have to be in possession of DAMES_SMR04_adv.
The primary difference between the advanced and basic
roles was in the variables that could be selected with
advanced roles having a much greater set of variables that
could be selected. The DAMES portal showing how it has
been configured using the CCP for an individual user with
advanced privileges is shown in Figure 1 (left) with the
results of running a query shown in Figure 1 (right). This
result data set shows the number of individuals who have
committed suicide across Scotland who have been at least
once to a hospital due to mental health related reasons. This
result data set also includes geospatial information. This
includes partial postcodes and/or output areas where the
individual lived or was treated at that time.</p>
        <p>Key to this approach is in understanding the actual data
sets themselves. That is, knowing what data sets in which
data resources are related. At present the clinical data sets
have a unique Community Health Index (CHI) number
associated with them. This unique variable was rolled out for
all individuals in receipt of health care across Scotland
mid2006. However, other data sets, e.g. the Census data, does
not including the CHI. Nevertheless there are other data
fields that are common, e.g. geospatial output area statistics.</p>
        <p>Building upon this information, DAMES has developed
further portlets that support overlaying this health related
data across geospatial boundaries. To support this, the
project has acquired shapemap files from EDINA
(www.edina.ac.uk) which can subsequently be used for
rendering and overlaying a variety of data across a given
geospatial boundary. These shapefiles cover health authorities
in Scotland and Scotland as a whole. The results of
overlaying the above data sets across Scotland are shown in Figure
3. We note that access to these shapefiles themselves is
restricted as they are under license to EDINA bu the
commercial organization Ordnance Survey. Thus access is only for
registered UK academics who have agreed to the terms and
conditions to the license.
To demonstrate the functionality of the SPAMP-GP ACP
portlet, we specifically defined a data service that had its
own local access and usage policy. Thus in reality, it is
highly unlikely that any given data provider will simply
delegate access to their data sets to a portal hosted at NeSC
in Glasgow. To address this, a local policy was defined and
enforced on access to the SMR99 data sets. In particular this
service would only allow access to the SMR99 data
variables for users with associated digitally signed and
recognised attribute certificates. Users would thus use the ACP
portlet to create an X509 attribute certificate based upon the
information that was delivered to the portal through
Shibboleth, i.e. the role that they need to use to access a particular
remote data set (in this case DAMES_SMR04_adv) would
need to be digitally signed and stored in an attribute
authority that the remote data provider trusts. In this case, the
attribute authority is an LDAP server associated with the
DAMES portal port.</p>
        <p>To support this process, the back end of the portal hosts a
Grid credential repository – a MyProxy server. This is
completely transparent to the user however. Thus the username
and password to activate the credential in the MyProxy
server is sent through as information as part of the
Shibboleth SAML assertion. This credential repository is used at
the individual invocation of a remote service. Thus the
service needs to identify the individual user attempting to
access the resource (authentication). Based on this they then
need to ensure that the user has the appropriate privileges to
run that particular query, i.e. pull the digitally signed
attribute certificate from the attribute authority that there local
policy recognises.</p>
        <p>
          More information on the DAMES work is described in
[
          <xref ref-type="bibr" rid="ref6 ref7">6-7</xref>
          ]. The project is currently applying for ethical
permissions to access and use actual SMR data sets to realise the
scenarios outlined previously.
        </p>
      </sec>
      <sec id="sec-4-2">
        <title>4.2 EuroDSD</title>
        <p>
          Disorders of sex development (DSD) are a set of disorders
affecting the genito-urinary tract and, in a lot of instances,
the endocrine-reproductive system. The physical
representations of DSD are manifest in different ways. In the case of
newborns this can be through children born with ambiguous
genitalia; in the case of teenagers this can be in their lack of
entry in to puberty. The condition is extremely rare and can
be a fraught and potentially stigmatizing condition for the
patients and families involved [
          <xref ref-type="bibr" rid="ref8">8</xref>
          ].
        </p>
        <p>
          At the heart of much DSD research is the androgen
receptor which is involved in controlling gene expression for
genes associated with DSD and in determining the sex
phenotype. In particular much DSD research is focused around
androgen receptor co-factors that modulate sex steroid
action [
          <xref ref-type="bibr" rid="ref9">9</xref>
          ].
        </p>
        <p>Given the rarity of the condition, there is an associated
scarcity of data on DSD. The EU funded EuroDSD project
(www.eurodsd.eu) has been established to help improve the
understanding and provision of therapy and potential
treatments or interventions associated with DSD, and increase
knowledge of the genetic and biochemical profiles which
characterize DSD. Until now, European research and the
data sets associated with DSD could best be categorized as
being fragmented. There was no possibility to co-ordinate
multiple, complementary DSD research areas in order to
make a significant step forward in the understanding of
DSD. Rather different centres and countries had their own
fragmented support networks for patients and their families.
The intention of EuroDSD is to bridge the gap between a
variety of disciplines including clinical medicine,
biochemistry, molecular genetics and molecular biology, through
cross-national integration of resources and expertise.
Currently, the EuroDSD project involves six European
countries including the UK, France, Netherlands, Germany, Italy
and Sweden.</p>
        <p>The central component of the EuroDSD project is the
development of a Virtual Research Environment (VRE),
designed to facilitate secure, flexible collaboration using
state of the art technologies. This technical work is led by
the National e-Science Centre (NeSC – www.nesc.ac.uk) in
Glasgow.</p>
        <p>The EuroDSD VRE currently comprises a portal which
hosts a registry which allows for secure upload and
searching of clinical case information. This information is based
on a common data model agreed through the European
Society for Paediatric Endocrinology (ESPE), and in particular
the work undertaken through the Scottish Genital Anomaly
Network (SGAN - http://www.sgan.nhsscotland.com/). An
example of this information is shown in Figure 3.
This information covers patient specific data including
the referring clinician; the year of birth of the patient and
specific clinical information and associated presentation
information. For example, whether the karyotype has been
established and if there are any further complications with
DSD – often DSD has other physiological presentations, e.g.
related to facial anomalies for example. The user interface
to upload patient specific information into the registry is
shown in Figure 4.</p>
        <p>We note that the system and data models have been
developed to be non-patient identifying. This has been a key
part in the work as a whole. The only identifying
information that exists in the registry is the contact details for the
clinician. An optional local patient identifier can also be
included, but once again the linkage of this with any given
individual cannot be achieved without detailed local
information on the patient itself. Indeed numerous other aspects
have been considered with regard to patient security. For
example, the data of birth has been refined to year of birth
only and exact birth weights have been refined to
approximate weights in kilograms. All of these considerations were
documented and put before ethics committees so that a
decision on data collection could occur. This agreement has now
happened and the data is being actively collected. At the
time of writing the registry contains patient data on 267
cases from numerous centres across Europe. There are
currently 40 registered users of the VRE from multiple sites. It
should also be noted that non-EuroDSD partners are also
now requesting access to the VRE to add their own clinical
data. This includes researchers from countries outwith the
European Union.</p>
        <p>Each patient that is entered into the system has a unique
registry identifier created and clinicians are expected to
keep a local record of this in case of future follow up from
collaborators, i.e. it is this information that can be used for
record linkage.</p>
        <p>The portal itself has been implemented using the Apache
Struts2 (http://struts.apache.org/2.x/) framework; the Spring
Framework (http://www.springsource.org/) and the
Hibernate framework (http://www.hibernate.org/). For maximum
flexibility, the portal has been based upon a multi-tiered
architecture. The upper layer is the user/presentation layer
and provides multiple ways to display information, e.g.
HTML, JSP, AJAX, etc. Other layers are used to control
targeted workflows and to process EuroDSD specific logic.
Finally the lower layer is used to give access to the DSD
data sets themselves and support for persistence itself.</p>
        <p>In this system architecture, Struts2 acts as the controller
of the VRE (aligned with the Model View Controller
paradigm) and provides presentation of the data. The Spring
framework provides a wide range of services for EuroDSD
business and workflow logics. Finally Hibernate, at the
lower layer, provides data persistence services to the VRE.</p>
        <p>This solution significantly improved the overall
flexibility, testability, and maintainability of the VRE. It was also
compatible with most existing frameworks and standards,
including JSR-168 portlets. Based on this n-tier architecture,
business logic is properly stripped from the presentation and
underlying data layers thus providing better maintainability
and enhancements. This model also allows further flexibility
for integration with further resources and tools.</p>
        <p>To improve system availability, dynamic VRE
configuration is support. Thus it is normally the case that changes of
configuration will typically require the restart of the Web
server containers hosting the services, and hence stopping
the services themselves. However, EuroDSD VRE
configuration is dynamic and can be loaded into the VRE through
scripts and property files.</p>
        <p>In terms of portal and VRE security, the Shibboleth
system is fully integrated into the VRE and everything inside of
the VRE runs through a Shibboleth-based authentication
process. One issue we have faced with this, is that users at
institutions that are not involved in a Access Management
Federation have been offered a virtual home at
NeSCGlasgow. This model works and has up to now been found
to scale reasonably well for local administrators. However
when the VRE is used by 100-1000’s of DSD researchers
then this modus operandi may need to be revisited.</p>
        <p>Based on consortium security requirements, each user has
been assigned with a set of EuroDSD-specific roles, which
are subsequently used for fine-grained access control. These
include EuroDSD_investigator; EuroDSD_contributor and
EuroDSD_researcher. These roles are subsequently used to
define and enforce the privileges of the user inside of the
portal. A user with the EuroDSD_contributor role has the
privilege to upload, edit, and withdraw cases in the registry,
whilst users assigned the EuroDSD_researcher role can
only search patient data. EuroDSD_investigators are able to
add, edit, delete and search data sets. In addition to these
roles, the project also supports the scope of the search. Thus
some sites are only able to add data for local centre users;
others only able to add data for national data sharing; others
for sharing across all of EuroDSD and others for all partners
in EuroDSD and potentially with other international
collaborators. The scope of data sharing is defined at data entry
time by the contributors as part of the consent process, i.e.
confirming that they have consent to add the patient data
and the level of data sharing that the consent allows.</p>
        <p>Every operation in the VRE (search, upload, edit, delete)
is secure and implemented according to roles assigned to
individuals. HTTPS is used to encrypt communications
between user browsers and the VRE, and between the VRE to
data sources. End users are completely oblivious of the
underlying security used to enforce access and use of clinical
data made available in the VRE.</p>
        <p>The VRE itself has also been developed with data
validation and usability aspects incorporated. Where possible,
selection boxes are used instead of text fields. This
simplifies data validation and ensures adherence with agreed data
formats (aligned with the ESPE core data model) and
avoiding data entry confusion. JavaScript is used in the user
interface to provide data validation and automatic calculations
when possible, e.g. calculating an External Masculinisation
Score based on user selections of five clinical fields. Invalid
data and actions are shown immediately when moving to
next data entry fields or on request submission. AJAX
technology is also used to provide coherent flow of information
without the need for page refreshing to interrupt user
experience.</p>
        <p>To support discussion and feedback between the scientists
involved in DSD, the VRE hosts a wiki. This wiki is directly
linked with the registry itself. Through the wiki, scientists
are able to directly comment on specific cases in the registry
and discuss aspects of the cases themselves or the treatment
of the individuals for example.</p>
        <p>The work on the EuroDSD VRE is still on-going. The
current work is focused upon genetic analysis modules.
These provide support for understanding the genetic
variations of children with DSD. This includes the genes that
have been screened for; the mutations/anomalies in genes
that have been found; whether further analysis of these
genes has been undertaken (including whether results have
been or are being published), as well as new and upcoming
screening and analysis methods, e.g. based upon mass
spectroscopy. The genetics analysis module also typifies the
structuring and standardization the EWuroDSD is
attempting to achieve. The field is characterized by multiple genes
with synonyms. To address this, the genetics analysis
module has implemented a core list of widely accepted genes
that the contributors can select. Thus textual editing has
been avoided to avoid typographical mistakes as well as
errors caused by upper/lower case genes representing
different genes.</p>
        <p>Further modules are also being explored. These include
modules specific to the surgical treatments of patients with
DSD. The classification of surgical treatments and the
outcomes of these treatments are subject to international
variation between partners.</p>
        <p>For centres with a catalogue of DSD cases, the effort to
manually enter these cases is off-putting. To address this we
are supporting systems that allow bulk upload of patient
data. The common technology that is used by most sites is
Excel. Services have been implemented that allow Excel
spreadsheets developed according to the ESPE core data
model to be automatically incorporated into the registry.</p>
        <p>Finally we note that some centres have their own local
databases and resources. We are in the process of make
these available through the EuroDSD VRE. These include
patient steroid and metabolomic databases for example.</p>
      </sec>
    </sec>
    <sec id="sec-5">
      <title>5 CONCLUSIONS AND FUTURE WORK</title>
      <p>
        The work described in this paper has outlined how
securityoriented portals can be supported that are aligned with the
requirements of a wide range of life science researchers and
communities. From experience of numerous projects in
NeSC we are acutely aware that usability of e-Infrastructure
has to be factored in from the outset. In this regard,
Shibboleth-based access, security-oriented portal configuration and
support for federated access control at remote, autonomous
data providers have been found to offer a model that is
closely aligned with many researcher user access
requirements. However we also recognize that these models are
often non-trivial for data providers such as the NHS. They
are for example, extremely reluctant to open up their
firewalls, irrespective of whether or not a service exists at their
side that has associated authorisation policies. Given this,
we are also exploring alternative data access and usage
models. This includes the VANGUARD system [
        <xref ref-type="bibr" rid="ref10">10</xref>
        ] that
has been demonstrated as a proof of concept system which
will be refined and hardened as part of the Wellcome Trust
funded Scottish Health Informatics Platform for Research
(SHIP) project.
      </p>
      <p>We also note that the work described here is also being
applied in numerous other research domains. This includes
the EPSRC funded nanoCMOS project
(www.nanocmos.ac.uk) and the recently funded ENROLLER
project (www.enroller.org.uk) and the NeISS project
(www.neiss.org.uk).</p>
    </sec>
    <sec id="sec-6">
      <title>ACKNOWLEDGEMENTS</title>
      <p>This work has been funded from a variety of sources including the
UK Engineering and Physical Sciences Research Council
(EPSRC), the Economic and Social Sciences Research Council
(ESRC), the European Union, the Joint Information Systems
Committee (JISC), the Medical Research Council (MRC) and the
Wellcome Trust. We gratefully acknowledge their support.</p>
    </sec>
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