Transcriptional profiling and network-based gene annotations of human malaria parasite plasmodium falciparum.
Hu, Guang An.
Date of Issue2009
School of Biological Sciences
Plasmodium falciparum is the most causative agent of the deadliest form of human malaria responsible for around 2 million deaths in the world. Even 6 years after the genome sequencing, more than 50 per cent genes of P. falciparum remain functionally uncharacterized. In this work we generated large functional datasets and systematically analyze these data combining other public functional datasets to characterize gene function, cellular process and gene regulation in P. falciparum. We developed the program OligoRankPick which uses a weighted rank-based strategy for the design of long oligonucleotide DNA microarrays. OligoRankPick does not rely on direct oligonucleotide exclusion by parameter cutoffs but instead optimizes all parameters in context of each other. Using this program we have designed several long oligonucleotide DNA microarrays for the parasitic species including P. falciparum, P. vivax and pan-rodent malaria. Based on the designed DNA microarray, we report on extensive transcriptional profiling of P. falciparum parasites using 20 small molecular compounds including several common antimalarial drugs. Diverse gene responses were observed in different drug or compound treatments and this perturbation data has a high predictive accuracy of functionally related genes based on their transcriptional regulation.
Nanyang Technological University