Abstract Background With the completion of the Human Genome Project and recent advancements in mutation detection technologies, the volume of data available on genetic variations has risen considerably. These data are stored in online variation databases and provide important clues to the cause of diseases and potential side effects or resistance to drugs. However, the data presentation techniques employed by most of these databases make them difficult to use and understand. Results Here we present a visualisation toolkit that can be employed by online variation databases to generate graphical models of gene sequence with corresponding variations and their consequences. The VariVis software package can run on any web server capable of executing Perl CGI scripts and can interface with numerous Database Management Systems and "flat-file" data files. VariVis produces two easily understandable graphical depictions of any gene sequence and matches these with variant data. While developed with the goal of improving the utility of human variation databases, the VariVis package can be used in any variation database to enhance utilisation of, and access to, critical information.</p

B Giardine

B Staats

C Béroud

C Kanz

CR Scriver

DA Benson

GP Patrinos

IFAC Fokkema

JE Stajich

JT den Dunnen

M Claustres

P Riikonen

RGH Cotton

Richard GH Cotton

SM Maurer

Timothy D Smith

English

PubMed

Crossref

VariVis: a visualisation toolkit for variation databases

BACKGROUND: With the completion of the Human Genome Project and recent advancements in mutation detection technologies, the volume of data available on genetic variations has risen considerably. These data are stored in online variation databases and provide important clues to the cause of diseases and potential side effects or resistance to drugs. However, the data presentation techniques employed by most of these databases make them difficult to use and understand. RESULTS: Here we present a visualisation toolkit that can be employed by online variation databases to generate graphical models of gene sequence with corresponding variations and their consequences. The VariVis software package can run on any web server capable of executing Perl CGI scripts and can interface with numerous Database Management Systems and "flat-file" data files. VariVis produces two easily understandable graphical depictions of any gene sequence and matches these with variant data. While developed with the goal of improving the utility of human variation databases, the VariVis package can be used in any variation database to enhance utilisation of, and access to, critical information

Smith, TD

Cotton, RGH

University of Melbourne Institutional Repository

BMC Bioinformatics

Springer - Publisher Connector

BioMed CentralBMC Bioinformatics
ssOpen AcceSoftware
VariVis: a visualisation toolkit for variation databases
Timothy D Smith*1,2 and Richard GH Cotton1,2
Address: 1Genomic Disorders Research Centre, Carlton South, VIC 3053, Australia and 2The University of Melbourne, Department of Medicine, 
Melbourne, VIC 3010, Australia
Email: Timothy D Smith* - t.smith6@pgrad.unimelb.edu.au; Richard GH Cotton - cotton@unimelb.edu.au
* Corresponding author    
Abstract
Background: With the completion of the Human Genome Project and recent advancements in
mutation detection technologies, the volume of data available on genetic variations has risen
considerably. These data are stored in online variation databases and provide important clues to
the cause of diseases and potential side effects or resistance to drugs. However, the data
presentation techniques employed by most of these databases make them difficult to use and
understand.
Results: Here we present a visualisation toolkit that can be employed by online variation databases
to generate graphical models of gene sequence with corresponding variations and their
consequences. The VariVis software package can run on any web server capable of executing Perl
CGI scripts and can interface with numerous Database Management Systems and "flat-file" data
files. VariVis produces two easily understandable graphical depictions of any gene sequence and
matches these with variant data. While developed with the goal of improving the utility of human
variation databases, the VariVis package can be used in any variation database to enhance utilisation
of, and access to, critical information.
Background
Although there has been effort over the last few years to
improve the quality of variation databases, with the
Human Genome Variation Society publishing guidelines
covering fields such as variant nomenclature [1], database
content, structure and deployment [2], and quality con-
trol [3], much of the data contained in variation databases
remains difficult to access. In a survey of locus specific
databases (LSDBs) in 2002, Claustres et al. noted that
only 54% of examined databases would fit minimal crite-
ria for ease of use, only "some" depicted the distribution
of variation within a gene and "few" possessed graphical
displays, especially of a dynamic nature [4]. Huge sums of
money have been invested in the search for the underlying
genetic causes of disease, but much of that investment is
wasted if anyone who desires the existing data is unable to
not only access, but also understand, what is being pre-
sented [5]. Variation databases are heavily underfunded
and usually run 'on the side' by researchers while pursuing
their funded research interests [6]. This lack of time and
money means that database curators often are unable to
devote the necessary time to developing useful visualisa-
tion tools. However, the data that languish in these data-
bases because they are so poorly presented could provide
answers to the cause of and assist clinicians in diagnosing
many human diseases if utilised effectively.
To encourage greater understanding and facilitate the
interpretation of data presented in the numerous locus
specific databases available on the internet, we have devel-
Published: 23 April 2008
BMC Bioinformatics 2008, 9:206 doi:10.1186/1471-2105-9-206
Received: 17 August 2007
Accepted: 23 April 2008
This article is available from: http://www.biomedcentral.com/1471-2105/9/206
© 2008 Smith and Cotton; licensee BioMed Central Ltd. 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), 
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Page 1 of 5
(page number not for citation purposes)
BMC Bioinformatics 2008, 9:206 http://www.biomedcentral.com/1471-2105/9/206oped software that will give the curators of variation data-
bases quick and easy access to some basic visualisation
tools.
In one sense, such visualisation tools are commonplace.
The UCSC Genome Browser [7] is an excellent tool for
viewing sequence annotations, providing both graphical
and text-based views. Users can view various annotation
sets, including cDNA evidence, predicted genes and varia-
tion data [7]. Genewindow, developed by the National
Cancer Institute, provides a gene-centric view of the
human genome specifically designed for variation visual-
isation [8].
However, these tools are of limited use to LSDB curators
as they do not enable them to easily utilise their own data
sets, which are often more complete than the published
literature [9], although the PhenCode project has gone
some way to mitigate the difficulty in loading an LSDB
into the UCSC Browser [10]. However, the requirement of
directing users away from the website of a locus specific
database in order to make use of these browsers is unde-
sirable and negates the benefits of the gene-specific infor-
mation that the majority of LSDBs offer above and
beyond variation data: 52% of locus specific databases
contain additional information on the diseases caused by
the catalogued variants and 34% provide clinical informa-
tion for both clinicians (91%), patients and their families
(66%) [4]. While incorporating variation data into
genome wide browsers is desirable, it does not replace the
need for data visualisation tools that can be incorporated
into an LSDB's own web site.
On the other hand, specialist variation database software
packages such as UMD [11] and MUTbase [12] that
include visualisation require curators to use a specific
database schema and user interface, which may not
always be practical or sufficient.
Implementation
VariVis is a collection of Perl scripts designed to provide a
basic set of visualisation tools specifically for LSDBs that
works in parallel with the existing user interface and data-
base of an LSDB and can access variation data stored in a
wide variety of formats including Database Management
Systems (DBMSs) such as MySQL, Oracle and Post-
greSQL, through to flat-file repositories such as comma or
tab delimited text files. LSDBs utilising the specialised var-
iation database software package LOVD [13], are espe-
cially suited to incorporating VariVis into their repertoire
of tools. Gene sequences and annotations can be accessed
from a locally stored file in any of a large number of
sequence file formats, including the FASTA, BSML and
GenBank formats (see Table 1); or VariVis can be directed
to automatically retrieve sequences from any of several
online sequence databases, such as GenBank [14] or
EMBL [15].
Upon each execution of the program, VariVis uses the
external BioPerl modules [16] to access the sequence data
and stores the nucleotide sequence and any available
structural annotations. The nucleotide sequence is then
automatically numbered according to the HGVS variation
numbering guidelines [17]. The Perl DBI module [18] is
then used to retrieve sequence variants from the database.
As each variant is added, a set of hand written regular
expressions are applied to the variant name in order to
determine the variant type and location. These regular
expressions are capable of recognising substitution, dele-
tion, insertion, duplication, insertion-deletion (indel)
and inversion events. More complex rearrangements are
currently planned for inclusion in a later release.
The graphics are rendered by a dedicated module using
basic HTML output to the user's browser.
Results
VariVis is capable of producing two different types of
graphical representations of the sequence and variation
data provided. Both views initially display an overview of
the gene structure, divided into introns and exons. Click-
ing on any of these divisions will display the selected
intron or exon in further detail.
The standard view (Figure 1) is reminiscent of traditional
sequence depictions, with the sequence broken up into
discrete chunks and stacked horizontally down the page.
Variant nucleotides are superimposed in red above the
gene sequence and their corresponding effect on the
amino acid sequence in red below the amino acid
sequence.
The second view (Figure 2), the "Gel View," has the same
functionality as the first viewing option, but this time ori-
entates the sequence vertically, allowing for an unbroken
Table 1: Compatible Sequence File Formats
ABI GenBank
ACE KEGG
ALF LocusLink
ASCIITree MetaFASTA
BSML PHD
CHADO PIR
CTF PLN
EMBL Qual
EXP Raw
FASTA SCF
FASTQ Tab
GAME TIGR
GCG ZTRPage 2 of 5
(page number not for citation purposes)
BMC Bioinformatics 2008, 9:206 http://www.biomedcentral.com/1471-2105/9/206stream of data. Theoretically, it is possible that any given
nucleotide in a gene can be mutated to any other nucle-
otide base, deleted entirely, or have an adjacent insertion.
Thus, the "Gel View" displays all possible nucleotide com-
binations for each position, a novel strategy, highlighting
the nucleotides present in the reference sequence and any
variations in contrasting colours. A horizontal version of
this format is also available (not shown).
In both views, the software also displays any structural
annotations, such as promoter sequences and UTRs as
bands of colour running in tracks alongside the gene
sequence. The software also provides access to the raw
sequence data, allowing users to copy or download the
entire sequence, or specific chunks, negating the need to
navigate to a dedicated sequence database. Clicking a var-
iant nucleotide provides the user with a brief overview of
the clinically important data present in the database for
the corresponding variant, from which the user can
choose to view the original report of the variant via
PubMed or perform a Google Scholar search for papers
discussing the variant.
Discussion
One of the major factors we took into consideration dur-
ing development of the VariVis package was ease of use,
not only for the database user, but also the curator. Once
the VariVis package is installed, it requires no further
action on behalf of the curator, allowing them to focus
entirely on collecting new data. As the graphics are gener-
ated dynamically at the time of viewing, new variants are
automatically included in the displays as soon as they are
added to the database. VariVis can be used to provide an
overall map of a gene of interest that users can explore at
their leisure, or to illustrate specific variants or features of
the gene by linking directly to specific areas within the
gene.
The program is easily installed by copying the source files
into any directory on a web server capable of executing
The standard view of VariVis displays the gene sequence horizontally across the screen with nucleotide variants above the sequence t ackFig re 1
The standard view of VariVis displays the gene sequence horizontally across the screen with nucleotide vari-
ants above the sequence track. Annotations are displayed as coloured tracks below the sequence with the amino acid 
sequence below; variation within the amino acid sequence is also displayed. On-screen tools allow the user to change the mag-
nification of the graphic, change the range being displayed or to switch between the two views.Page 3 of 5
(page number not for citation purposes)
BMC Bioinformatics 2008, 9:206 http://www.biomedcentral.com/1471-2105/9/206CGI scripts, and then configured using the provided
installation script.
The study of genetic variation has and will continue to
yield remarkable health benefits for all humans, and
while the data currently available in online variation data-
bases are extremely valuable, the data presentation meth-
ods employed make accessing and understanding those
data very difficult. As the number of variation databases
expands and more variants are discovered, the need for
better presentation methods will become more apparent.
It has been argued that the amount of data that will even-
tually be generated from a complete catalogue of all pos-
sible genetic variants will outstrip the data generated by
the Human Genome Project [9]. It is interesting to note
then, that while "fancy tools" for displaying sequence data
exist in the form of genome browsers such as the UCSC
browser [7], very few tools currently exist for displaying
sequence variation. While the variation database manage-
ment software packages UMD [11] and MUTbase [12] do
contain some visualisation tools, these tools are only
available to the users of these particular database software
packages. Visualisation tools are not available to database
curators who cannot, or have chosen not to use these sys-
tems.
Conclusion
There is a lack of visualisation tools for variation data that
can be implemented on any database system. The VariVis
The "Gel" View displays the gene sequence vertically, reminiscent of old sequencing gelsFigure 2
The "Gel" View displays the gene sequence vertically, reminiscent of old sequencing gels. Variants are highlighted 
in red. Clicking on a variant will display a brief summary alongside the sequence.Page 4 of 5
(page number not for citation purposes)
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software package is an attempt to rectify this situation by
providing database curators with a visualisation tool capa-
ble of easily combining the highly curated variation data
within LSDBs with sequence and annotation data regard-
less of their underlying database and user interface. While
developed with the study of human variation in mind, the
VariVis software package could be implemented in data-
bases devoted to the cataloguing of variation within any
species, particularly viruses, parasites and plants.
Very soon, the Human Variome and the myriad of health
consequences it engenders will be fully described and
annotated [19,20]. Novel systems need to be developed to
allow fast and efficient access and use of the enormous
volumes of data and information that will be generated
and available, often to those less familiar with these data-
bases. The system described here is a first step towards
accomplishing efficient and useful access to these vital
databases, and goes some way to satisfying recommenda-
tion D6 of the Human Variome Project [19].
Availability and Requirements
Project name: VariVis
Project home page: http://
www.genomic.unimelb.edu.au/varivis
Operating system(s): Platform independent
Programming language: Perl
Other requirements: BioPerl and Perl DBI external mod-
ules (available via CPAN)
License: see http://www.genomic.unimelb.edu.au/var
ivis/license.html
Any restrictions to use by non-academics: Commercial
use license can be obtained by contacting the authors
Authors' contributions
TS carried out the programming and software design and
drafted the manuscript. RC conceived of the study, and
participated in its design and coordination and helped to
draft the manuscript. All authors read and approved the
final manuscript.
Acknowledgements
The authors wish to acknowledge the help of William Appelbe for his useful 
discussions and support. This work was supported by the NHMRC (RC) 
and the Helen Smibert Vacation Scholarship (TS).
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Abstract Background With the completion of the Human Genome Project and recent advancements in mutation detection technologies, the volume of data available on genetic variations has risen considerably. These data are stored in online variation databases and provide important clues to the cause of diseases and potential side effects or resistance to drugs. However, the data presentation techniques employed by most of these databases make them difficult to use and understand. Results Here we present a visualisation toolkit that can be employed by online variation databases to generate graphical models of gene sequence with corresponding variations and their consequences. The VariVis software package can run on any web server capable of executing Perl CGI scripts and can interface with numerous Database Management Systems and "flat-file" data files. VariVis produces two easily understandable graphical depictions of any gene sequence and matches these with variant data. While developed with the goal of improving the utility of human variation databases, the VariVis package can be used in any variation database to enhance utilisation of, and access to, critical information.</p

Smith Timothy D

Cotton Richard GH

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Paalman MH: Standardizing mutation nomenclature: why bother? Human Mutation

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VariVis: a visualisation toolkit for variation databases

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