Clostox: A Clostridium Toxin Database and Phylogeny Viewer for Pathema-Clostridium
Seth Schobel, Susmita Shrivastava, Erin Beck, Lauren Brinkac, Tanja Davidsen, Granger Sutton
J. Craig Venter Institute, 9704 Medical Center Dr. Rockville, MD, 20850 USA
Abstract
Pathema-Clostridium (http://pathema.jcvi.org) is a clade specific NIAID
Bioinformatics Resource Center designed to support the Clostridium biodefense
and infectious disease research community. Pathema-Clostridium targets the
detailed curation of Clostridium botulinum and C. perfringens, but also includes all
other available Clostridium sequenced genomes. After IBRCC 2007 and extensive
polling of the Clostridium research community it was determined that a
comprehensive database of all Clostridium toxin genes would be an effective
extension of the Pathema resource. As a result of this community feedback we
have developed Clostox, a Clostridium toxin database, and integrated it with the
current Pathema-Clostridium web resource. A literature search was performed to
identify all the toxin genes associated with Clostridium botulinum strains. The
protein sequences were downloaded from NCBI and processed through the JCVI’s
annotation pipeline and curated. Additionally, each protein was blasted against all
other proteins in the Pathema-Clostridium database to incorporate informative
comparative analyses into the Clostox repsoitory. To leverage the addition of
Clostox to Pathema, we have developed an integrated tool for viewing the
phylogeny of toxin sequences, both from the Clostox database and from a user-
specified list. This allows for classification of unidentified strains for which the
neurotoxin sequence is known. The tool has been expanded to benefit Pathema as
a whole by accepting input from the Protein vs. All Alignment page of any gene, as
well as from the Gene Cart.
Overview
Pathema-Clostridium, as part of the Bioinformatics Resource Center, is a
community research portal designed to suit the needs of the community. In
response to the community’s request for a tool oriented toward toxin research, the
J. Craig Venter Institute (JCVI) has created CLOSTOX. Clostox is web resource
available through Pathema-Clostridium. Underlying the web resource is a database
containing Clostridium toxin gene annotation data. The set of genes currently
available on Clostox consists of Clostridium botulinum toxins from serotypes A, B,
C, D, E, F and G; as well as physiological groups I, II, III, and IV. The toxin genes
are thus divided into nine serotype groups: group I (A, B, F), group II (B, E, F),
group III (C, D) and group IV (G). The main advantage of collecting toxin genes in
one repository is that JCVI is able to apply consistent annotations and annotation
Clostox Tools:
data types to the entire set of publicly available toxin genes. This consistency
allows for more informative comparison between the various toxin annotations by
•Toxin Search
the utilization of a common set of terms and evidence types. Furthermore, each of
the toxin genes has been run through Pathema’s all vs all protein analysis. This
•Blast
allows Clostox to display a pre-computed functional comparison of each toxin gene
against all proteins in Pathema-Clostridium. As with all genes found on Pathema,
•Phylogeny Viewer
Clostox gene annotations can be updated to include community annotations. In
addition to annotation data, there are several tools integrated into the site that allow
for tailored toxin research. First, a CLOSTOX GENE SEARCH has been adapted to
Future Development
display gene collections in any of the nine serotype groups. Next, Clostox supports
BLAST searches against all of the Clostox protein sequences. Finally, CLOSTOX
PHYLOGENY VIEWER, a multiple sequence alignment and tree drawing tool has been In the coming months JCVI plans on expanding the Clostox database by adding toxin
integrated to Clostox. This tool allows for phylogenetic comparisons of the toxin genes from Clostridium perfringens and Clostridium butyricum. In addition to adding
protein sequences. Clostox Phylogeny Viewer has three gateways and currently these toxin genes, NAPs will be added to the database across the entire Clostridium
uses ClustalW to generate the multi sequence alignment. The main gateway is a clade. Routine updates will be made to reflect updates to current Clostox annotation
stand alone page that allows the user to choose between all, one, or any and inclusion of additional toxin and NAP genes as they are released publicly. The
combination of serotype groups and draws a rooted dendrogram. Similarly, the Clostox web resource is slated for enhancements to include a synonymous
user may provide their own protein sequences to generate a tree using the accessions search available from the Clostox Toxin Search, as well as a strain
sequences from any or all of the nine serotype groups. Multiple sequence search. The phylogeny viewer will be enhanced with the option to use T-Coffee to
alignments are also available through the Protein vs. All link, accessible from the generate alignments for tree generation in addition to ClustalW.
gene page for each toxin. The GENE CART is the last gateway to the phylogeny tool.
Contact Us
With this approach a user can place all the genes of which they are interested into
Acknowledgments
We are actively soliciting feedback from
their cart and generate a tree from just those protein sequences. As with all data
the community. Please e-mail
and tools on Pathema-Clostridium, users have the option to download all gene and
clostridium@jcvi.org if you have any
protein sequences, annotation data, and analysis results associated with the
We wish to acknowledge the efforts of Sean Daugherty from the University of
Clostox resource. suggestions or data corrections.
Maryland School of Medicine. This project is funded by The National Institute of
Allergy and Infectious Diseases (NIH-NIAID-DMID-04-34).