BIOINFORMATICS APPLICATIONS NOTE
Vol. 18 no. 2 2002
Interactive InterPro-based comparisons of
proteins in whole genomes
A. Kanapin∗, R. Apweiler, M. Biswas, W. Fleischmann,
Y. Karavidopoulou, P. Kersey, E. V. Kriventseva, V. Mittard,
N. Mulder, T. Oinn, I. Phan, F. Servant and E. Zdobnov
EMBL Outstation, The European Bioinformatics Institute, Wellcome Trust Genome
Campus, Hinxton, Cambridgeshire CB10 1SD, UK
Received on March 2, 2001; revised and accepted on September 27, 2001
Motivation: The SWISS-PROT group at the EBI has de-
veloped the Proteome Analysis Database utilizing existing
resources and providing comprehensive and integrated
comparative analysis of the predicted protein coding
sequences of the complete genomes of bacteria, archaea
and eukaryotes. The Proteome Analysis Database is
accompanied by a program that has been designed to
carry out interactive InterPro proteome comparisons for
any one proteome against any other one or more of the
proteomes in the database.
Contact: firstname.lastname@example.org; email@example.com
Genome sequencing is proceeding at an increasingly
rapid rate and this has led to an equally rapid increase
in predicted protein sequences entering the protein
sequence databases. In this paper the term proteome is
used to describe the protein equivalent of the genome.
Most of these predicted protein sequences are without a
documented functional role. One of the major challenges
of the genome era is to predict molecular functions and
biological roles for the predicted gene products.
There are a number of existing databases that ad-
dress some aspects of genome comparisons. The Kyoto
Encyclopedia of Genes and Genomes (KEGG) is a
knowledge base for systematic analysis of gene functions,
linking genomic information with higher order func-
tional information (Kanehisa and Goto, 2000). The WIT
Project attempts to produce metabolic reconstructions for
sequenced (or partially sequenced) genomes (Overbeek
et al., 2000). A metabolic reconstruction is described as
a model of the metabolism of the organism derived from
sequence, biochemical, and phenotypic data. KEGG and
WIT mainly address regulation and metabolic pathways
although the KEGG scheme is being extended to include
∗To whom all correspondence should be addressed.
a number of non-metabolism-related functions. A phy-
logenetic classification of proteins encoded in more than
30 complete genomes can be found in the Clusters of
Orthologous Groups of proteins (COGs; Tatusov et al.,
2000). COGs group together related proteins with similar
but sometimes non-identical functions
InterPro (http://www.ebi.ac.uk/interpro/) is an in-
tegrated documentation resource of protein families,
domains and functional sites that rationalizes the com-
plementary efforts of the PROSITE, PRINTS, Pfam and
ProDom database projects. InterPro is implemented as a
relational database in Oracle and users have direct access
via Java servlets. The InterPro database is distributed as
XML-formatted flat files and as exports of the relational
database. The InterPro database provides an integrated
layer on top of the most commonly used signature
databases to provide a user-friendly interface for text-
based searches and sequence scans. In the present paper
we describe an important tool that facilitates dynamic
InterPro based comparative analysis of each proteome
with other available proteomes allowing flexibility of
access to the data and providing the means to generate
Comparative analysis data is presented in two different
versions in the proteome analysis database (Apweiler et
al., 2001a,b) as static and dynamic HTML pages. The
static HTML pages contain a few of the most obvious
proteome comparisons and these are listed in the section
below. This comparison is run through the proteome
comparison program and the data is updated weekly
together with all other proteome analysis updates. The
dynamic HTML pages are generated interactively using
the InterPro proteome comparisons program.
Dynamic InterPro-based comparisons can be made us-
ing the InterPro proteome comparisons program to select
the proteomes of the organisms to be compared and the
type of comparative analysis to be carried out (http://www.
ebi.ac.uk/proteome/comparisons.html). The program is a
c ? Oxford University Press 2002
InterPro proteome comparisons Download full-text
Fig. 1. The top section of the form used for setting up interactive InterPro-based comparisons of proteins in whole genomes.
web application with a client/server architecture that runs
on a UNIX server and is accessed via a web browser (e.g.
Netscape) from any computer that has access to the server
via internet. Users can set up the dynamic comparison us-
ing a simple input form (Figure 1). The Java servlet cre-
ates an SQL script for the selected proteomes and analysis
type (as selected by the user) and runs it over the Oracle
database. The results are formatted and presented as web
pages, similar to the static HTML pages.
Comparisons that can be made include general statistics,
top 30 entries, top 200 entries, 15 most common protein
families, 15 most common domains and 15 most common
protein repeats. An additional feature is the option to
compute a list of shared InterPro entries that are common
to all the selected proteomes (this is similar in concept to
the overlapping region of a Venn diagram).
Apweiler,R., Biswas,M., Fleischmann,W., Kanapin,A., Karavi-
dopoulou,Y., Kersey,P., Kriventseva,E.V., Mittard,V., Mulder,N.,
Phan,I. and Zdobnov,E. (2001a) Proteome analysis database: on-
line application of InterProand CluSTr for the functional clas-
sification of proteins in wholegenomes. Nucleic Acids Res., 29,
Apweiler,R., Attwood,T.K., Bairoch,A., Bateman,A., Birney,E.,
Biswas,M., Bucher,P., Cerutti,L., Corpet,F., Croning,M.D.R.,
jakob,H., Hulo,N., Jonassen,I., Kahn,D., Kanapin,A., Kar-
avidopoulou,Y., Lopez,R., Marx,B., Mulder,N.J., Oinn,T.M.,
Pagni,M., Servant,F., Sigrist,C.J.A. and Zdobnov,E.M. (2001b)
The InterPro database, an integrated documentation resourcefor
protein families, domains and functional sites. Nucleic Acids
Res., 29, 37–40.
Kanehisa,M. and Goto,S. (2000) KEGG: Kyoto Encyclopedia of
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Overbeek,R., Larsen,N., Pusch,G.D., D’Souza,M., Selkov,E. Jr,
integrated system for high-throughput genome sequenceanalysis
and metabolic reconstruction. Nucleic Acids Res., 28, 123–125.
Rubin,G.M., Yandell,M.D., Wortman,J.R., Gabor Miklos,G.L., Nel-
son,C.R., Hariharan,I.K., Fortini,M.E., Lip,W., Apweiler,R.,
Fleischmann,W. et al. (2000) Comparative genomics of the eu-
karyotes. Science, 287, 2204–2215.
Snel,B., Bork,P. and Huynen,M. (2000) Genome evolution: gene
fusion versus gene fission. Trends Genet., 16, 9–11.
Tatusov,R.L., Galperin,M.Y, Natale,D.A. and Koonin,E.V. (2000)
The COG database: a tool for genome-scale analysis of protein-
functions and evolution. Nucleic Acids Res., 28, 33–36.