An integrated approach to understand apicomplexan metabolism from their genomes

Background

The Apicomplexa is a large phylum of intracellular parasites that show great diversity and adaptability in the various ecological niches they occupy. They are the causative agents of human and animal infections including malaria, toxoplasmosis and theileriosis, which have a huge economic and social impact. A number of apicomplexan genomes have been sequenced and are publicly available. However, the prediction of gene models and annotation of gene functions remains challenging.

Methods

We have utilised an approach called ‘metabolic reconstruction’, in which genes are systematically assigned to functions within pathways/networks [1–4]. Functional annotation and metabolic reconstruction was carried out using a semi-automatic approach, integrating genomic information with biochemical evidence from the literature. The functions were automatically assigned using a sequence similarity-based approach and protein motif information. Experimental evidence was also accommodated in the confirmation of functions and the grouping of genes into metabolic pathways.

Results

A web database named Library of Apicomplexan Metabolic Pathways (LAMP, http://www.llamp.net) [5] was developed to deposit the reconstructed metabolic pathways of Toxoplasma gondii, Neospora caninum, Cryptosporidium and Theileria species and Babesia bovis. Each metabolic pathway page contains an interactive metabolic pathway map, gene annotations hyperlinked to external resources and detailed information about the metabolic capabilities. This analysis led to the identification of missing enzymes that must be present to complete the metabolic pathway and orphan genes (incorrect enzyme annotations or enzymes that are involved in salvage of metabolites) that are isolated in pathways that are otherwise absent. The compilation and annotation of metabolic pathways and the comparative analysis of the overall metabolic capabilities of apicomplexan species enabled identification of differences in their ability to synthesise or depend on hosts for several metabolites (Table 1, Additional file 1).

Table 1 A survey of the data available for the different apicomplexan genomes in LAMP. The analysis is updated from the survey table published in the previous publication [5]

Conclusions

The carefully annotated metabolic pathways and the comparative analysis of metabolism for eight apicomplexan species are publicly available for the research community in the LAMP database (http://www.llamp.net). This has improved the functional annotation immensely and led to identification of putative drug targets. The hyperlinks for LAMP metabolic pathway annotations are available from the respective gene pages of the T. gondii primary database, ToxoDB (release 9) [6], enabling a wider reach for LAMP.