An orthology-based analysis of pathogenic protozoa impacting global health: an improved comparative genomics approach with prokaryotes and model eukaryote orthologs.

A key focus in 21(st) century integrative biology and drug discovery for neglected tropical and other diseases has been the use of BLAST-based computational methods for identification of orthologous groups in pathogenic organisms to discern orthologs, with a view to evaluate similarities and differences among species, and thus allow the transfer of annotation from known/curated proteins to new/non-annotated ones. We used here a profile-based sensitive methodology to identify distant homologs, coupled to the NCBI's COG (Unicellular orthologs) and KOG (Eukaryote orthologs), permitting us to perform comparative genomics analyses on five protozoan genomes. OrthoSearch was used in five protozoan proteomes showing that 3901 and 7473 orthologs can be identified by comparison with COG and KOG proteomes, respectively. The core protozoa proteome inferred was 418 Protozoa-COG orthologous groups and 704 Protozoa-KOG orthologous groups: (i) 31.58% (132/418) belongs to the category J (translation, ribosomal structure, and biogenesis), and 9.81% (41/418) to the category O (post-translational modification, protein turnover, chaperones) using COG; (ii) 21.45% (151/704) belongs to the categories J, and 13.92% (98/704) to the O using KOG. The phylogenomic analysis showed four well-supported clades for Eukarya, discriminating Multicellular [(i) human, fly, plant and worm] and Unicellular [(ii) yeast, (iii) fungi, and (iv) protozoa] species. These encouraging results attest to the usefulness of the profile-based methodology for comparative genomics to accelerate semi-automatic re-annotation, especially of the protozoan proteomes. This approach may also lend itself for applications in global health, for example, in the case of novel drug target discovery against pathogenic organisms previously considered difficult to research with traditional drug discovery tools.

ProtozoaDB: dynamic visualization and exploration of protozoan genomes.

ProtozoaDB (http://www.biowebdb.org/protozoadb) is being developed to initially host both genomics and post-genomics data from Plasmodium falciparum, Entamoeba histolytica, Trypanosoma brucei, T. cruzi and Leishmania major, but will hopefully host other protozoan species as more genomes are sequenced. It is based on the Genomics Unified Schema and offers a modern Web-based interface for user-friendly data visualization and exploration. This database is not intended to duplicate other similar efforts such as GeneDB, PlasmoDB, TcruziDB or even TDRtargets, but to be complementary by providing further analyses with emphasis on distant similarities (HMM-based) and phylogeny-based annotations including orthology analysis. ProtozoaDB will be progressively linked to the above-mentioned databases, focusing in performing a multi-source dynamic combination of information through advanced interoperable Web tools such as Web services. Also, to provide Web services will allow third-party software to retrieve and use data from ProtozoaDB in automated pipelines (workflows) or other interoperable Web technologies, promoting better information reuse and integration. We also expect ProtozoaDB to catalyze the development of local and regional bioinformatics capabilities (research and training), and therefore promote/enhance scientific advancement in developing countries.