Evidence-based annotation of the malaria parasite's genome using comparative expression profiling

A fundamental problem in systems biology and whole genome sequence analysis is how to infer functions for the many uncharacterized proteins that are identified, whether they are conserved across organisms of different phyla or are phylum-specific. This problem is especially acute in pathogens, such...

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Published in:	PloS one Vol. 3; no. 2; p. e1570
Main Authors:	Zhou, Yingyao, Ramachandran, Vandana, Kumar, Kota Arun, Westenberger, Scott, Refour, Phillippe, Zhou, Bin, Li, Fengwu, Young, Jason A, Chen, Kaisheng, Plouffe, David, Henson, Kerstin, Nussenzweig, Victor, Carlton, Jane, Vinetz, Joseph M, Duraisingh, Manoj T, Winzeler, Elizabeth A
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 13-02-2008 Public Library of Science (PLoS)
Subjects:	Animals Aquatic insects Baking yeast Biosynthesis Blood Cell interactions Comparative analysis Computational Biology - methods Computational Biology/Genomics Computational Biology/Systems Biology Computational Biology/Transcriptional Regulation Data collection Erythrocytes Fatty acids Gene expression Gene Expression Profiling Gene regulation Genes Genetic aspects Genetics and Genomics Genetics and Genomics/Gene Expression Genome, Protozoan Genomes Genomics Gliding Humans Infectious Diseases/Protozoal Infections Insects Life cycle analysis Life cycle engineering Life Cycle Stages - genetics Life cycles Liver Malaria Mathematical models Microbiology/Microbial Evolution and Genomics Microbiology/Microbial Growth and Development Microbiology/Parasitology Nucleotide sequence Parasites Physiological aspects Plasmodium falciparum Plasmodium falciparum - genetics Probabilistic models Protein interaction Protein Interaction Domains and Motifs Protein-protein interactions Proteins Protozoan Proteins - genetics Protozoan Proteins - physiology Saccharomyces cerevisiae Salivary gland Sporozoites Transcription Transcription (Genetics) Vector-borne diseases Yeast Yeasts La Jolla California New York California United States > US Massachusetts
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Summary:	A fundamental problem in systems biology and whole genome sequence analysis is how to infer functions for the many uncharacterized proteins that are identified, whether they are conserved across organisms of different phyla or are phylum-specific. This problem is especially acute in pathogens, such as malaria parasites, where genetic and biochemical investigations are likely to be more difficult. Here we perform comparative expression analysis on Plasmodium parasite life cycle data derived from P. falciparum blood, sporozoite, zygote and ookinete stages, and P. yoelii mosquito oocyst and salivary gland sporozoites, blood and liver stages and show that type II fatty acid biosynthesis genes are upregulated in liver and insect stages relative to asexual blood stages. We also show that some universally uncharacterized genes with orthologs in Plasmodium species, Saccharomyces cerevisiae and humans show coordinated transcription patterns in large collections of human and yeast expression data and that the function of the uncharacterized genes can sometimes be predicted based on the expression patterns across these diverse organisms. We also use a comprehensive and unbiased literature mining method to predict which uncharacterized parasite-specific genes are likely to have roles in processes such as gliding motility, host-cell interactions, sporozoite stage, or rhoptry function. These analyses, together with protein-protein interaction data, provide probabilistic models that predict the function of 926 uncharacterized malaria genes and also suggest that malaria parasites may provide a simple model system for the study of some human processes. These data also provide a foundation for further studies of transcriptional regulation in malaria parasites.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Conceived and designed the experiments: JV EW YZ MD VR KK SW PR JY FL. Performed the experiments: DP VR KK SW PR JY KH FL. Analyzed the data: EW YZ. Contributed reagents/materials/analysis tools: JV YZ VN MD JC BZ KC. Wrote the paper: EW YZ.
ISSN:	1932-6203 1932-6203
DOI:	10.1371/journal.pone.0001570