Plasmobase: a comparative database of predicted domain architectures for Plasmodium genomes

Abstract

Background: With the availability of complete genome sequences of both human and non-human Plasmodium parasites, it is now possible to use comparative genomics to look for orthology across Plasmodium species and for species specific genes. This comparative analyses could provide important clues for the development of new strategies to prevent and treat malaria in humans, however, the number of functionally annotated proteins is still low for all Plasmodium species. In the context of genomes that are hard to annotate because of sequence divergence, such as Plasmodium, domain co-occurrence becomes particularly important to trust predictions. In particular, domain architecture prediction can be used to improve the performance of existing annotation methods since homologous proteins might share their architectural context.

Results: Plasmobase is a unique database designed for the comparative study of Plasmodium genomes. Domain architecture reconstruction in Plasmobase relies on DAMA, the state-of-the-art method in architecture prediction, while domain annotation is realised with CLADE, a novel annotation tool based on a multi-source strategy. Plasmobase significantly increases the Pfam domain coverage of all Plasmodium genomes, it proposes new domain architectures as well as new domain families that have never been reported before for these genomes. It proposes a visualization of domain architectures and allows for an easy comparison among architectures within Plasmodium species and with other species, described in UniProt.

Conclusions: Plasmobase is a valuable new resource for domain annotation in Plasmodium genomes. Its graphical presentation of protein sequences, based on domain architectures, will hopefully be of interest for comparative genomic studies. It should help to discover species-specific genes, possibly underlying important phenotypic differences between parasites, and orthologous gene families for deciphering the biology of these complex and important Apicomplexan organisms. In conclusion, Plasmobase is a flexible and rich site where any biologist can find something of his/her own interest.

Availability: Plasmobase is accessible at http://genome.lcqb.upmc.fr/plasmobase/ .

Keywords: Annotation; Database; Domain architecture prediction; Genome; Genome comparison; Plasmodium; Protein architecture.

Fig. 1

Newly predicted domain architecture of P. falciparum gene PF3D7_1369500. Plasmobase “Look up” page associated to gene PF3D7_1369500. CLADE predicted architecture (top) contains three domains: MIF4G, MIF4G_like_2, MIF4G_like. Pfam_27 architecture is displayed below and it highlights no identified domains. The list of all domains identified by CLADE is given. Besides the three domains belonging to CLADE architecture, there is one more domain displayed in grey that has been also identified by CLADE but not selected by DAMA. The user might be interested to consider it in view of a putative functional annotation of the protein. Indeed, he/she can select a combination of CLADE domains and explore it either in Plasmobase or in UniProt by clicking on the corresponding buttons (bottom). The list of orthologs and paralogs, according to PlasmoDB, can be displayed by clicking on the “show” link. Windows with informations on identified domains (Pfam domain name, Pfam accession number, CLADE model species, position of the domain in the protein, domain coverage, E-value, CLADE SVM probability, clan name if any) are accessible by passing the mouse above the domain location, as illustrated by the information box for the blue domain. Note that the clade-centred model generated by the Bombix mori MIF4G_like sequence is the one that obtained the best match with Plasmodium sequence PF3D7_1369500

Fig. 2

Proteins with similar architectures explored in Plasmobase/UniProt. a All Plasmodium species contain a protein sequence sharing the same CLADE architecture as PF3D7 1369500. A selection of these species allows to explore these protein sequences in Plasmobase, and verify information for domain architecture identification in other species. The whole list of domains is reported (in this specific example, there is only one architecture per species). b Plasmobase allows to explore the UniProt database for architectures that are similar to the one identified by CLADE for PF3D7 1369500. There are similar architectures in Metazoa, Fungi, Viridiplantae and other clades. A selection of Fungi and Viridiplantae allows the user to compare the architectures among these clades. Fungi contains 41 sequences with the given architecture and the full list is accessible