Full text of DOI:10.1093/bioinformatics/17.9.847

Vol. 17 no. 9 2001
Pages 847–848
BIOINFORMATICS APPLICATIONS NOTE
InterProScan – an integration platform for the
signature-recognition methods in InterPro
Evgeni M. Zdobnov ∗ and Rolf Apweiler
EMBL Outstation, European Bioinformatics Institute, Wellcome Trust Genome
Campus, Hinxton, Cambridge CB10 1SD, UK
Received on August 2, 2000; revised on January 12, 2001; accepted on May 30, 2001
ABSTRACT
INTERPRO MEMBER DATABASES AND
Summary: InterProScan is a tool that scans given protein
sequences against the protein signatures of the InterPro
member databases, currently – PROSITE, PRINTS, Pfam,
ProDom and SMART. The number of signature databases
and their associated scanning tools as well as the further
refinement procedures make the problem complex. Inter-
ProScan is designed to be a scalable and extensible sys-
tem with a robust internal architecture.
Availability: The Perl-based InterProScan implementation
is available from the EBI ftp server (ftp://ftp.ebi.ac.uk/pub/
software/unix/iprscan/) and the SRS-based InterProScan
is available upon request. We provide the public web
interface (http://www.ebi.ac.uk/interpro/scan.html) as well
as email submission server (interproscan@ebi.ac.uk).
Contact: Evgueni.Zdobnov@EBI.ac.uk
SCANNING METHODS
Legend: ❖ denotes a database and ➢ denotes the associ-
ated scanning tools.
❖PROSITE patterns. Some biologically significant
amino acid patterns can be summarized in the form of
regular expressions.
➢ ScanRegExp (by Wolfgang.Fleischmann@ebi.ac.uk).
❖PROSITE profiles based on weight matrices (also
known as profiles) are more sensitive in detection of
divergent protein families.
➢ pfscan from the Pftools package
(by Philipp.Bucher@isrec.unil.ch).
❖PRINTS database houses a collection of protein family
fingerprints. These are groups of motifs that together are
diagnostically more potent than single motifs by making
use of the biological context inherent in a multiple-motif
method.
INTRODUCTION
Databases of protein domains and functional sites have
become vital resources for the prediction of protein
functions. During the last decade, several signature-
recognition methods have evolved to address different
sequence analysis problems, resulting in rather different
and, for the most part, independent databases. Diagnos-
tically, these resources have different areas of optimum
application owing to the different strengths and weak-
nesses of their underlying analysis methods. Thus, for best
results, search strategies should ideally combine all of
them. InterPro (The InterPro Consortium, 2001) is a col-
laborative project aimed at providing an integrated layer
on top of the most commonly used signature databases
by creating a unique, non-redundant characterization of
a given protein family, domain or functional site. The
InterPro database integrates PROSITE (Hofmann et al.,
1999), PRINTS (Attwood et al., 2000), Pfam (Bateman
et al., 2000), ProDom (Corpet et al., 1999) and SMART
(Schultz et al., 2000) databases and the addition of others
is scheduled.
➢ FingerPRINTScan (Scordis et al., 1999).
❖Pfam is a database of protein domain families. Pfam
contains curated multiple sequence alignments for each
family and corresponding profile hidden Markov models
(HMMs).
➢ hmmpfam from the HMMER2.1 package
(by Sean Eddy, eddy@genetics.wustl.edu,
http://hmmer.wustl.edu),
DeCypherTM (TimeLogic) HMM search.
❖ProDom families are built by an automated process
based on a recursive use of PSI-BLAST homology
searches.
➢BlastProDom.pl (by Florence Servant,
fservant@toulouse.inra.fr) a filter on top of the Blast
package (Altschul et al., 1997).
❖SMART domains are extensively annotated with respect
to phyletic distributions, functional class, tertiary struc-
tures and functionally important residues. SMART align-
ments are optimised manually and following construction
of corresponding Hidden Markov Models (HMMs).
➢ hmmpfam from the HMMER2.1 package,
DeCypherTM (TimeLogic) HMM search.
∗
To whom correspondence should be addressed.
c
ꢀ Oxford University Press 2001
847

E.M.Zdobnov and R.Apweiler
in other stand-alone ad-hoc solutions. The Perl-based
InterProScan is capable of providing post-processed,
integrated results in several formats and it could be
used as a simple retrieval system for the underlying
data.
The tool has become popular in the bioinformatics
community. The EBI public web interface serves more
than 10 000 interactive requests a month. There are
more than 60 installations worldwide of the Perl-based
InterProScan package that has already been used to
analyse the complete genomes on a production scale.
INTERPROSCAN
InterProScan is a tool that combines different protein sig-
nature recognition methods into one resource. The number
of signature databases and their associated scanning tools
as well as the further refinement procedures increase the
complexity of the problem. InterProScan is more than a
simple wrapping of sequence analysis applications since
it requires performing a considerable data look-up from
some databases and program outputs. The need for pro-
duction scale efficiency and an easy extensibility require
a robust and efficient (parallel) internal architecture that
can benefit from network distributed computing with the
support of UNIX queueing systems.
ACKNOWLEDGEMENTS
We developed an SRS-based InterProScan suite as well
as the stand-alone Perl-based InterProScan package.
Nowadays SRS (Etzold et al., 1996) has become an inte-
gration system for both data retrieval and applications for
data analysis that is ideally suited to resolve the data flow
complexity in InterProScan. Firstly, InterProScan was im-
plemented using the introduced technique of joining some
of the SRS integrated applications into one virtual appli-
cation that can organize the execution of the underlying
steps in an efficient (parallel) manner. Later, we devel-
oped a client web interface using the SRS Perl API that
is a compromise between the SRS inter-database linking
integrity and the simplicity of the user interface, providing
‘one-click-away’ results.
While the SRS-based InterProScan has several benefits
from the close integration with other databases it requires
some SRS expertise and is bound to the licensed SRS
distribution. To overcome these limitations we decided
to develop a stand-alone InterProScan version based
on the popular scripting language Perl. The Perl-based
InterProScan was intended as an extensible and scalable
system optimised to cope with bulk data processing. In
the package a Perl-based simple data retrieval system
was introduced to provide the required data look-up
efficiency and easy extensibility. The system has a mod-
ular structure and is designed in an SRS-like fashion.
Each of the data description modules defines the data
schema of the source text data and the parsing rules. The
corresponding Perl module provides an object-oriented
interface to the underlying entry attributes. The parsing
of the source data into the memory objects happens only
once and is done upon request, implementing so-called
lazy-parsing. Hierarchical parsing rules are implemented
using the recursive-descent approach (Parse-RecDescent
package). Fast data retrieval is implemented using the Perl
native B-trees indexing (DB File.pm, based on Berkeley
DB). The simple ‘one Perl module per data source’
organisation makes it possible to reuse the modules
We would like to thank Rodrigo Lopez for general support
and the mailserver backend as well as Thure Etzold and
Henning Hermjakob for useful discussions and ideas.
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