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Progress in in silico functional genomics: the malaria Metabolic Pathways database

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Genomic, transcriptomic and proteomic data can be turned into biologically meaningful information if they are synthesized into processes. Such amalgamation has been done for the most virulent malaria parasite Plasmodium falciparum in the Metabolic Pathways database. The dialectics of construction of metabolic pathways and other biological processes using this database is presented here. Additional features, such as links to other databases and the incorporation of transcriptomic clocks, are elucidated. Comparison of Metabolic Pathways to other similar databases is analyzed.

Section snippets

A profusion of data

The genome project of Plasmodium falciparum was completed in 2002, although some annotations of specific genes are being constantly added. Other plasmodial genomes are currently being sequenced and nearing completion, while additional information that is needed for a meaningful biological interpretation of the genomic data, such as transcriptomics and proteomics, is being generated. This has already led to the generation of some tools by the developers of PlasmoDB (see Box 1a; and from there to

Construction of a website

There are several websites of metabolic processes available. The most comprehensive are loaded with information that is not relevant for malaria parasites. In constructing MPMP, the relevant information was extracted and displayed in an educative and informative format (Figure 1). The templates for the well-known metabolic pathways were obtained from KEGG (Box 1d) and trimmed to remove irrelevant entries. Some maps in MPMP are an amalgamation of several KEGG maps to give a more comprehensive

Transcriptomic clocks

Additional information has been added to the metabolic maps (see Figure 1); next to each entry there is a 48-h clock that depicts the stage-dependent transcription of the gene coding this entry. The clock is a spatial transformation of the linear strips as they appear in the DeRisi/UCSF transcriptome database (Box 1e). Thus, at the clock's zero hour, the merozoite invades, and at 12 o'clock, the 48-h-long cycle terminates. In the middle of the clock appears the hour of maximal transcript level.

Plasmodium-relevant data from other websites

Searching in KEGG for P. falciparum (pfa), yields 77 maps, many of which are not relevant for the parasite metabolism because they include very few enzymes and those included do not form a continuous pathway. Some of the pathways are conspicuously irrelevant from their name (e.g. under Biodegradation of Xenobiotics) and others can be identified with a glance even by the non-expert. But true identification requires a map-by-map scrutiny. The other shortcoming of KEGG is the absence in the

Summary

MPMP has been enhanced during the past year with several new tools – transcriptome clocks, links to chemical reactions and to GeneDB – and many new maps have been added. The maps were constructed with the aim that they could be used for teaching and at the same time serve as a functional context-oriented synthesis for individual gene products for researchers. Unlike other Plasmodium-related databases, MPMP was developed, and is curated and further expanded, manually. Its maintenance is strongly

Acknowledgements

The website is presently supported by the Computation Authority of The Hebrew University of Jerusalem, Israel (http://www.huji.ac.il/huji/eng/info_computers_e.htm) and by the BioMalPar Network of Excellence on Biology and Pathology of the Malaria Parasite supported by a grant (LSHP-CT-2004–503578) in the 6th Framework Programme of the EU (http://www.biomalpar.org/).

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