Nucleic Acids Research Advance Access originally published online on November 5, 2007
Nucleic Acids Research 2008 36(Database issue):D543-D546; doi:10.1093/nar/gkm928
Nucleic Acids Research, 2008, Vol. 36, Database issue D543-D546
© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
xBASE2: a comprehensive resource for comparative bacterial genomics
Roy R. Chaudhuri,
Nicholas J. Loman,
Lori A.S. Snyder,
Christopher M. Bailey,
Dov J. Stekel and
Mark J. Pallen*
Centre for Systems Biology, University of Birmingham, Birmingham B15 2TT, UK
*To whom correspondence should be addressed. Tel: +44 121 414 7163; Fax: +44 121 414 3454; Email: m.pallen{at}bham.ac.uk
Received September 18, 2007. Accepted October 10, 2007.
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ABSTRACT
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xBASE is a genome database aimed at helping laboratory-based
bacteriologists make best use of bacterial genome sequence data,
with a particular emphasis on comparative genomics. The latest
version,
xBASE 2.0 (
http://xbase.bham.ac.uk), now provides comprehensive
coverage of all bacterial genomes and features an updated modularized
backend and an improved user interface, which includes a taxonomy
browser and a powerful full-text search facility.
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INTRODUCTION
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xBASE grew out of
coliBASE,
CampyDB and several similar projects,
which were restricted to selected taxonomic groups of bacteria
(
1,
2). In its initial implementation,
xBASE was simply an umbrella
term applied to a set of distinct databases that relied on a
similar schema. In creating
xBASE2, we have developed a new
integrated, comprehensive bacterial genomes database, with greatly
increased coverage, many new features and an improved user interface
and code base.
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FEATURES
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The implementation of a scalable
xBASE schema has allowed us
to incorporate all bacterial genome sequences available from
the NCBI (currently >800), including finished genomes and
partially assembled genomes from the WGS division of GenBank.
At the time of writing, 516 complete genome sequences and 367
draft genome sequences are included in the database, with the
total number expected to reach well over 1000 by the end of
2007. The current design is intended to scale to at least 10
000 genomes. The database is updated monthly via an automated
process so that new genome sequence data are incorporated into
xBASE soon after they are released into the public domain. A
numerical scheme for naming updates allows researchers to record
and cite the particular version of
xBASE used in their studies.
The wealth of data within xBASE presents new challenges in locating a genome sequence of interest. The user interface provides a number of options to address this problem. The xBASE top page contains a complete list of the included genomes, which can be filtered to a more manageable list of ‘popular’ genomes, where popularity is determined by hit rate of each genome sequence, i.e. is set by the xBASE user community. A taxonomy browser is provided, which can be toggled between a full taxonomy view and a list of popular taxa. Although xBASE2 maintains the identities of the earlier databases (coliBASE, CampyDB, etc.) to facilitate the transition to the new version for our current user base, these are now merely flags of convenience for a small subset of all potential taxon-specific views. For example, the coliBASE tab takes the user to set of genomes defined by the link from the taxon Enterobacteriaceae. However, users now can select their genome sets of interest from any point on the NCBI bacterial taxonomic hierarchy, from phyla such as Actinobacteria to subspecies like Zymomonas mobilis subsp. mobilis. Genome sequences can also be located using the full-text search facility, with results ranked on the popularity of the organism.
The number of genomes within xBASE2 means that pre-calculating all pairwise genome sequence alignments is now no longer feasible. Instead, MUMmer (3) alignments are now performed on demand, within seconds, and are cached so that they are redisplayed instantly. Nucleotide alignments are now performed using the nucmer component of MUMmer. This has the advantage over mummer in that it allows comparisons between multiple-contig genomes, which is particularly useful when working with unfinished genomes. The alignment display code has been modified to allow multiple pairwise comparisons to be stacked, so that the same region can be viewed in many different genome sequences (Figure 1).
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Figure 1. Stacked alignment of regions from multiple Escherichia coli and Shigella genomes. The region displayed shows the ‘black hole’ deletion of the cadA gene from the Shigella genomes. The product of this gene has been shown to attenuate Shigella virulence (5).
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An XY plot allows the plotting of data such as nucleotide composition
and principal axes derived from correspondence analysis of relative
synonymous codon usage data (
Figure 2). This facilitates identification
of genes that show unusual patterns of composition or codon
usage that might be indicative of horizontal gene transfer.
The graphical display of genomic regions now includes genomic
coordinates and at high zoom nucleotide sequences are displayed
(
Figure 3). Circular chromosomes and plasmids are now handled
correctly, so the display can wrap around the origin of the
sequence. An
xBASE blog has been launched, with regular contributions
from the development team, including status updates, discussions
of new features and requests from users for additional functionality.
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Figure 2. Plot of the two principal axes determined by correspondence analysis of relative synonymous codon usage of genes from E. coli strain 536. The plot shows a typical ‘rabbit's head’ (6), with the right ‘ear’ corresponding to highly expressed genes with optimal codon usage. The left ‘ear’ includes genes likely to be of foreign origin, most of which show a low GC content.
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Figure 3. Alignment of two Staphylococcus aureus genomes, zoomed in to show the nucleotide sequence. The MW2 gene MW1571, which encodes a tRNA methyltransferase, is split into two in the NCTC 8325 genome. The display indicates that this is due to a single base deletion that occurs in a run of 5 T residues, suggesting that it may be an artefact caused by a sequencing error.
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XBASE2 IMPLEMENTATION
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The
xBASE database backend has been completely rewritten to
make use of a modified BioSQL schema, with additional tables
to allow storage of genome alignment data and a flattened annotation
table to aid rapid full-text searching. The code has also been
modularized. The streamlined code brings benefits both to maintainers
and end user, allowing new features to be developed rapidly
and delivering a significant improvement in response time. Performance
has also been improved by investment in new hardware. The full-text
indexing facilities offered by the tsearch2 component of Postgresql
have proven vital in creating a fast, accurate search facility.
Researchers can now rapidly search for text strings such as
gene names, phrases and keywords within both genome annotation
and the documentation associated with each genome in the
Genomes online database (GOLD) (
4).
xBASE source code and database is
freely available on request.
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FUTURE CHALLENGES
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xBASE is funded until 2012. A key challenge will be maintaining
usability in the face of thousands of new genome sequences,
which are likely to be delivered within this timeframe by the
application of next-generation sequencing to bacteriology. Within
xBASE, multiple stacked pairwise comparisons will have to be
supplemented with a view that collapses down identical regions
and only shows representative displays of syntenic regions.
Another challenge will be integration of experimental data (e.g.
microarray and chromatin immunoprecipitation data) and networks
(e.g. of protein–protein interactions) into the
xBASE
facility. Work has already begun on
xBASE 3.0, which will feature
a new ‘Web 2.0’ user interface exploiting AJAX and
advanced browser visual layout techniques, so that different
data sets can be overlain and manipulated on the same page as
a ‘mashup’ and full zooming and panning across a
genome become possible (as in Google Maps). User tracking will
enable us to provide a personalized interface, which will include
a community annotation facility. We are thus confident that
xBASE will continue to serve the bacteriology community well
into the second decade of the new millennium.
xBASE is available
at
http://xbase.bham.ac.uk.
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ACKNOWLEDGEMENTS
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Funding to pay the Open Access publication charges for this
article was provided by BBSRC. This work is supported by the
BBSRC, grant number BBE0111791, awarded to MJP and DJS.
Conflict of interest statement. None declared.
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Footnotes
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Present address: Roy R. Chaudhuri, Cambridge Veterinary School,
University of Cambridge, Cambridge CB3 0ES, UK
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REFERENCES
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- Chaudhuri RR, Pallen MJ. xBASE, a collection of online databases for bacterial comparative genomics. Nucleic Acids Res. (2006) 34:D335–D337.[Abstract/Free Full Text]
- Chaudhuri RR, Khan AM, Pallen MJ. coliBASE: an online database for Escherichia coli, Shigella and Salmonella comparative genomics. Nucleic Acids Res. (2004) 32:D296–D299.[Abstract/Free Full Text]
- Kurtz S, Phillippy A, Smoot M, Shumway M, Antonescu C, Salzberg SL. Versatile and open software for comparing large genomes. Genome Biol. (2004) 5:R12.[CrossRef][Medline]
- Liolios K, Tavernarakis N, Hugenholtz P, Kyrpides NC. The Genomes On Line Database (GOLD) v.2: a monitor of genome projects worldwide. Nucleic Acids Res. (2006) 34:D332–D334.[Abstract/Free Full Text]
- Maurelli AT, Fernandez RE, Bloch CA, Rode CK, Fasano A. ‘Black holes’ and bacterial pathogenicity: a large genomic deletion that enhances the virulence of Shigella spp. and enteroinvasive Escherichia coli. Proc. Natl Acad. Sci. USA (1998) 95:3943–3948.[Abstract/Free Full Text]
- Medigue C, Rouxel T, Vigier P, Henaut A, Danchin A. Evidence for horizontal gene transfer in Escherichia coli speciation. J. Mol. Biol. (1991) 222:851–856.[CrossRef][ISI][Medline]
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