Transcriptional profiling of growth perturbations of the human malaria parasite Plasmodium falciparum

• Published in: Nature biotechnology Vol. 28; no. 1; pp. 91 - 98
• Main Authors: Hu, Guangan, Cabrera, Ana, Kono, Maya, Mok, Sachel, Chaal, Balbir K, Haase, Silvia, Engelberg, Klemens, Cheemadan, Sabna, Spielmann, Tobias, Preiser, Peter R, Gilberger, Tim-W, Bozdech, Zbynek
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2010; Nature Publishing Group
• Subjects: Agriculture; Algorithms; Animals; Antimalarial agents; Antimalarials; Antimalarials - pharmacology; Artemisinin; Biochemistry; Bioinformatics; Biomedical Engineering/Biotechnology; Biomedicine; Biotechnology; Causes of; Developmental biology; Gene expression; Gene Expression Profiling; Gene Expression Regulation - drug effects; Gene Regulatory Networks; Genes; Genetic aspects; Growth; Guilt (Psychology); Health aspects; Homology; Humans; Life Sciences; Malaria; Malaria, Falciparum - parasitology; Markov Chains; Merozoites - drug effects; Merozoites - metabolism; Novels; Parasites; Perturbation; Plasmodium falciparum; Plasmodium falciparum - drug effects; Plasmodium falciparum - genetics; Plasmodium falciparum - growth & development; Plasmodium falciparum - pathogenicity; Proteins; Protozoan Proteins - metabolism; resource; Transcription (Genetics); Transcription, Genetic - drug effects; Vaccines; Vector-borne diseases; Yeast; Yeasts; Germany
• ISSN: 1087-0156; 1546-1696; 1546-1696
• DOI: 10.1038/nbt.1597

We have yet to identify the functions of the majority of genes of Plasmodium falciparum , the causative agent of malaria. Hu et al . profile transcriptional changes after chemically induced growth perturbations to assemble a protein network that predicts P. faliciparum gene function. Functions have yet to be defined for the majority of genes of Plasmodium falciparum , the agent responsible for the most serious form of human malaria. Here we report changes in P. falciparum gene expression induced by 20 compounds that inhibit growth of the schizont stage of the intraerythrocytic development cycle. In contrast with previous studies, which reported only minimal changes in response to chemically induced perturbations of P. falciparum growth, we find that ∼59% of its coding genes display over three-fold changes in expression in response to at least one of the chemicals we tested. We use this compendium for guilt-by-association prediction of protein function using an interaction network constructed from gene co-expression, sequence homology, domain-domain and yeast two-hybrid data. The subcellular localizations of 31 of 42 proteins linked with merozoite invasion is consistent with their role in this process, a key target for malaria control. Our network may facilitate identification of novel antimalarial drugs and vaccines.