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

• DOI: 10.1038/nbt.1597
• Publication Date: 2009-12-27T18:03:09Z
• Authors: Guangan Hu; Ana Cabrera; Maya Kono; Sachel Mok; Balbir K Chaal; Silvia Haase; Klemens Engelberg; Sabna Cheemadan; Tobias Spielmann; Peter R Preiser; Tim-W Gilberger; Zbynek Bozdech
• Keywords: 0301 basic medicine; Transcription, Genetic; Merozoites; Gene Expression Profiling; Plasmodium falciparum; Protozoan Proteins; Markov Chains; 3. Good health; Antimalarials; 03 medical and health sciences; Gene Expression Regulation; Animals; Humans; Gene Regulatory Networks; Malaria, Falciparum; Algorithms

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 approximately 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.