Metabolic reconstruction and analysis for parasite genomes

John W. Pinney, Balázs Papp, Christopher Hyland, Lillian Wambua, David R. Westhead, Glenn A. McConkey
2007 Trends in Parasitology  
With the completion of sequencing projects for several parasite genomes, efforts are ongoing to make sense of this mass of information in terms of the gene products encoded and their interactions in the growth, development and survival of parasites. The emerging science of systems biology aims to explain the complex relationship between genotype and phenotype by using network models. One area in which this approach has been particularly successful is in the modeling of metabolism. With an
more » ... te picture of the set of metabolic reactions encoded in a genome, it is now possible to identify enzymes or transporters that might be viable targets for new drugs. Because these predictions greatly depend on the quality and completeness of the genome annotation, there are substantial efforts in the scientific community to increase the numbers of metabolic enzymes identified. In this review, we discuss the opportunities for using metabolic reconstruction and analysis tools in parasitology research, and their applications to protozoan parasites. Metabolic reconstruction in post-genomic parasitology Genome sequencing projects have been undertaken for numerous protozoan parasites, and much sequence information is now publicly available. Complete genome sequences have been published for several Apicomplexa (including two Plasmodium species [1,2], Cryptosporidium parvum [3] and Cryptosporidium hominis [4]) and the trypanosomatids Trypanosoma cruzi [5], Trypanosoma brucei [6] and Leishmania major [7] . Sequencing of several other protozoan, helminth and parasitic nematode genomes is ongoing, and data are publicly available. Published genome annotations provide initial predictions of the metabolic enzymes, and preliminary genome-scale metabolic reconstructions (see Glossary) for Plasmodium falciparum and the trypanosomatids have been produced [6, 8] . Genome annotation and metabolic reconstruction can be considered complementary efforts: isolated enzymatic functions are likely to indicate false-positive annotations, whereas missing enzymes in otherwise complete pathways might represent as-yet unassigned gene functions. The annotation of parasitic genomes is difficult owing to their great divergence and compositional bias, but funds are lacking for complete manual curation of several neglected organisms. Owing to these difficulties, the scientific community has been enlisted to assist curation of the parasite genomes available at present [9] . For some industrially significant prokaryotes, the analysis of reconstructed metabolic networks has already proved useful; for example, in increasing the production of a desired metabolic product [10] . In the context of a pathogenic organism, however, metabolic reconstruction has the potential to play an important part in the drug discovery
doi:10.1016/j.pt.2007.08.013 pmid:17950669 fatcat:chzvhyqcqze5tefcyi6monjy6a