Biotechnological
Communication
Biosci. Biotech. Res. Comm. 10(2): 13-18 (2017)
Edi ce of vitiDB: A  rst ever structured portal for
vitiligo protein repository and its assessment
Anvita Gupta Malhotra, Sudha Singh, Mohit Jha and Khushhali M Pandey*
Department of Biological sciences and Engineering, MANIT, Bhopal (M.P) INDIA
ABSTRACT
vitiDB (http://vitidb.com/index.php) is the  rst ever structured repository exclusively for vitiligo disorder. This portal
brings together valuable but heterogeneous or disparate information available from a spectrum of public domain
databases, patents and published literature sources on vitiligo. The aim is to arm the research community with criti-
cal details extracted froma reviewed resource of vitiligo genes and proteins. In addition, the database throws light
on interectome of proteins and their targetability assessment. The current release of vitiDB contains 333 vitiligo
disease - associated proteins and nearly 5000 allied proteins. Each entry provides comprehensive data related to the
protein like its kinetic, pharmacological and ontological properties. Additionally, this portal provides browsing and
extracting information related to vitiligo protein interaction network and its topological properties. vitiDB catalogues
107416 unique interactions among 4845 proteins derived from 8 different databases. Detailed targetability analysis is
available at this portaland it includes druggability, assayability, essentiality, vulnerability and secretability analysis
for the disease proteins. This user-friendly web interface will help the user to have an informed opinion on disease
genes without having to plough through various databases. The additional information in the form of derived data
can potentially assist in the drug discovery process. There will be sustained effortsaimed at periodic updation of the
core data in the wake of their extension / modi cation as well as constructive feedback received from the users.
KEY WORDS: VITILIGO, INTERACTION NETWORK, TARGETABILITY, DRUGGABILITY, DATABASE
13
ARTICLE INFORMATION:
*Corresponding Author: kmpbiomanit@gmail.com,
khushhalimenariya@manit.ac.in
Received 27
th
Nov, 2016
Accepted after revision 26
th
Jan, 2017
BBRC Print ISSN: 0974-6455
Online ISSN: 2321-4007 CODEN: USA BBRCBA
Thomson Reuters ISI ESC and Crossref Indexed Journal
NAAS Journal Score 2017: 4.31 Cosmos IF : 4.006
© A Society of Science and Nature Publication, 2017. All rights
reserved.
Online Contents Available at: http//www.bbrc.in/
14 VITIDB: VITILIGO PROTEIN REPOSITORY AND ASSESSMENT PORTAL BIOSCIENCE BIOTECHNOLOGY RESEARCH COMMUNICATIONS
Anvita Gupta Malhotra et al.
Introduction
Vitiligo is a progressive depigmentation disorder affect-
ing nearly 1% of the world population (Guerra et al.,
2010). Vitiligo disorder is characterized by progressive
skin depigmentation phenomena, which is induced and
maintained by the loss of melanin - producing cells
at the cutaneous level. Vitiligo is known to be a skin
disorder with complex etiology. Its pathogenesis and
the inner causes are still unclear but, in recent years,
scienti c research identi ed various pathways and
processes for its onset and progression. There are sev-
eral proposed hypotheses for this depigmenting dis-
order which includes autoimmunity auto-cytotoxic/
metabolic mechanisms, (Reimann et al., 2012), and
impaired melanocyte migration and/or prolifera-
tion (Westerhof and d'Ischia, 2007, Speeckaert et al.,
2015).
Studies also show the important role played by genetic
susceptibility in the origin of vitiligo. These mechanisms
are neither mutually exclusive, noradequate enough to
explain the disease etiology on their own. An integrated
viewpoint can be formed by incorporating all the differ-
ent causal factors that could contribute to some extent to
melanocyte destruction into a ‘convergence theory’ (Le
Poole et al., 1993), (Schallreuter et al., 2008, Jin et al.,
2016, Spritz, 2011). Vitiligo involves a complex frame-
work of interactions between various proteins, pathways
and processes (Laddha et al., 2013). An attempt has been
made here to bring together these disease proteins on
a common platform to display their related properties.
Further protein-protein interaction (PPI) data for each
of these disease proteins were extracted to generate a
comprehensive vitiligo interectome map (Malhotra et al.,
2017).
Information regarding the interectome analysis is
also made readily available on this portal.A better
understanding of the disease could provide new targets
for prevention or treatment of vitiligo (Passeron and
Ortonne, 2012). An ideal drug target should compre-
hend following properties: favourable assayability for
high throughput screening, ability to modify a disease,
less effect on alteration of physiological conditions or
other diseases, differential expression across the body,
the availability of a biomarker, etc. Experimentally
evaluating all proteins for their targetability is an over-
whelming task (Gashaw et al., 2011, Dey-Rao and Sinha,
2017).
Hence, it’s not experimentally possible to analyse
and prioritize all the drug targets in a laboratory. This
necessitates employinga computational technique for
evaluation of proteins on the standards of potent drug
targets (Sakharkar and Sakharkar, 2007, Costa et al.,
2010, Kandoi et al., 2015). Thus targetability analysis of
these proteins will aid in shortlisting prospective thera-
peutic drug targetsfrom the entire proteome with high
speci city.
There is no exclusive database for vitiligo disease
proteins available till date. All related information is dis-
persed in various published literature and online data-
bases and is, therefore, extremely dif cult to access. For
assisting the vitiligo researchers, all scattered data has
been compiled together and adedicated and comprehen-
sive vitiligo proteins repository – vitiDB - is developed.
Methodology
Data collection and compilation
The organization of data was done systematically as pri-
mary and derived data [Figure-1]. The primary data con-
sists of the vitiligo disease proteins related information.
The secondary data includes disease proteins interaction
data and its analysis features. Alongside the targetability
related parameters were also computed and added to the
resource.
Disease Protein Information
In order to build a comprehensive resource for vitiligo
proteins an extensive search was carried out across vari-
ous online databases like NCBI (2017), Uniprot (2015),
AnyGene [AnyGenes® http://www.anygenes.com/index.
php], Harmonizome (Rouillard et al., 2016), vitivar [http://
vitivar.igib.res.in/genes], GeneCards (Rebhan et al.,
1998), DOlite (Du et al., 2009), DisGeNET (Pinero et al.,
2015), OMIM (Hamosh et al., 2005), Disease Ontology
(Schriml et al., 2012) and Human Phenotype Ontology
(Kohler et al., 2014). Along with these databases, infor-
mation was also manually curated from published lit-
erature, microarray experiments and SNP analysis. Gene
susceptibility studies (Passeron and Ortonne, 2005),
(Picardo et al., 2015) were also considered while collat-
ing the disease genes for vitiligo.
Vitiligo Interectome Data
PPI data for the disease proteins were extracted from
eight different databases. These includes BioGrid (Chatr-
Aryamontri et al., 2015), MINT (Ceol et al., 2010),
STRING (Szklarczyk et al., 2017), Reactome (Croft et al.,
2014), DIP (Xenarios et al., 2002), IntAct (Kerrien et al.,
2012), Spike (Paz et al., 2011) and GeneMania (Zuberi
et al., 2013). All this data was merged and the unique
interactions were employed for construction of unidirec-
tional vitiligo interaction map (Malhotra et al., 2017) in
Cytoscape (Kohl et al., 2011).
BIOSCIENCE BIOTECHNOLOGY RESEARCH COMMUNICATIONS VITIDB: VITILIGO PROTEIN REPOSITORY AND ASSESSMENT PORTAL 15
Anvita Gupta Malhotra et al.
FIGURE 1. Architecture of vitiDB.
Cytoscape is a highly versatile program for the analy-
sis, operation and visualization of large networks. Later,
the topological properties (Degree, Betweeness centrality,
Topological coef cient, Clustering coef cient, Closeness
centrality, Radiality, Stress, Neighbourhood connectivity
and Average shortest path length) were calculated for
all the proteins in the map. These calculation were done
in Network Analyzer (Assenov et al., 2008), an inbuilt
plugin with cytoscape that is used for comprehensive
analysis of network topologies.
Targetability statistics for disease proteins
The key disease proteins were analysed for their ability
to be a good therapeutic target (Rask-Andersen et al.,
2011). This was done under  ve heads namely Drugga-
bility (Druggable Genome (Hopkins and Groom, 2002),
can SAR druggability (Bulusu et al., 2014), DrugBank
(Law et al., 2014), DGI druggability (Grif th et al., 2013),
PDTD (Gao et al., 2008) and Domain DrugEBIlity (EMBL)
[https://www.ebi.ac.uk/chembl/drugebility/]) Assay-
ability (Sigma Aldrich database, Brenda (Schomburg
et al., 2017), Ki database [https://kidbdev.med.unc.edu/
databases/kidb.php], PDB (Berman et al., 2000) or Bind-
ing DB (Gilson et al., 2016)), Essentiality (OGE (Chen
et al., 2012), MGD (Eppig et al., 2007), Human Pheno-
type project (Kohler et al., 2014), Part et al. (Park et al.,
2008) or Georgi et al. (Georgi et al., 2013)), Vulnerability
(Holme et al., 2002) and Secretability (Narayanan, 2015).
Database architecture and web interface development
All the collated data were entered in excel  les which
were converted into csv  les. These  les were later
imported into MySQL database. MySQL, an object-rela-
tional open source database management system, was
employed to manage the data at the back-end. There were
11 tables in the database. The database was launched
using Apache HTTP server online on Linux Platform and
on local machine via WAMP server 2.0. For the backend
support i.e., database interfacing scripts, we have used
PHP programming language. It queries backend data-
base to retrieve information. The front end was designed
using HTML 5.
Results and Discussion
Implementation
The database is sectioned into three categories: Vitiligo
Protein Repository, Vitiligo Interectome map and Targ-
etability Analysis. All the information can be browsed
under the sections mentioned below (Figure-2).
16 VITIDB: VITILIGO PROTEIN REPOSITORY AND ASSESSMENT PORTAL BIOSCIENCE BIOTECHNOLOGY RESEARCH COMMUNICATIONS
Anvita Gupta Malhotra et al.
FIGURE 2. Schematic representation of vitiDB web interface.
Vitiligo Protein Repository:
A total of 333 disease proteins were identi ed. Their
related information is made available from this section
under the following features:
Basic Information- This includes Gene name, Pro-
tein name, Uniprot id, status, Length of the protein,
gene name synonyms and also the source from which
this protein is obtained as vitiligo disease protein. This
source can be related to protein or pathway in which
the protein is involved like database, microarray experi-
mentation, autoimmunity, susceptibility studies, apop-
tosis, melanogenesis (Singh et al., 2013) or oxidative
stress.
Kinetic properties – Enzyme related information is
displayed here under the headings EC number, Catalytic
activity, KineticsPathway, Enzyme regulation, Active
site, Binding site, Site or Function.
Ontology Data – Gene Ontology details and identi-
ers are made available.
PubmedDetails – Pubmed ids for the corresponding
protein is mentioned.
Cross-reference to other online databases - The vitil-
igo protein entries are linked to other biological data-
bases like PDB, SMR, Protein Model Portal, PDB-
sum, DisProt, STRING, MINT, IntAct, DIP, BioGrid, Guide
to PHARMACOLOGY, DrugBank, ChEMBL, BindingDB,
KEGG, GeneID, Ensembl, BRENDA, BioCyc, Reactome,
InterPro, PRINTS, PROSITE, Pfam, DisGeNET, Gene-
Cards, PharmGKB or GeneWiki.
Vitiligo Interaction Map
The disease proteins interaction network consists of
4845 nodes and 107416 unique interactions. The inter-
acting partners along with the topological properties are
available for each of 4845 proteins. Further, based on
the network topology analysis, the proteins were clas-
si ed as backbone and core proteins and are labeled
accordingly in the database under the section
Classi ca-
tion of proteins.
Targetability Analysis of Disease proteins
A comprehensive description of all the features pertain-
ing to the drug target identi cation was fetched from
various sources and displayed under this head. The pro-
teins that are in alignment with most of the parameters
are entitledto be the prospective target for the vitiligo
disorder. The later updates will aim at making the tar-
getability analysis available for all the human proteins.
Concluding Remarks
The increasing amount of data on protein interactions,
drug target features,and the knowledge of drug-like
properties can act as a very lucrative starting point for
vitiligo drug hunt. Vitiligo sufferers still have to face
ostracism and discrimination around the world. This is a
modest attempt to aid in its treatment. The enriched data
and search utilities available at vitiDB might assist other
BIOSCIENCE BIOTECHNOLOGY RESEARCH COMMUNICATIONS VITIDB: VITILIGO PROTEIN REPOSITORY AND ASSESSMENT PORTAL 17
Anvita Gupta Malhotra et al.
online databases in providing all-inclusive information
about the drugs, targets and target identi cation proc-
ess aimed at further research and drug discovery efforts.
Availability
vitiDBis a free database that can be accessed at http://
vitidb.com
Acknowledgments
The authors thankfully acknowledge the help, support
and guidance provided by Dr. Ajay Pandey, Department
of Mechanical Engineering, MANIT, Bhopal.
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