Interactive Transcriptome Analysis of Malaria Patients and Infecting Plasmodium falciparum in Indonesia

To understand the mutual association of the transcriptomes between host humans and infecting malaria parasites, Plasmodium falciparum (Pf), in vivo, we conducted the RNA-Seq analysis of 116 Indonesian malaria patients. Using RNAs extracted from peripheral blood of the patients as the mixture of the human and Pf transcripts, we generated a total of 3 billion RNA-Seq tags. Analysis of these tags allowed us to identify genes and pathways which were associated with clinical symptoms both on human and parasite sides. Particularly, we observed characteristic expression changes in the human innate immune response pathway genes depending on severity of malaria. We also identified a group of transcription regulatory factors and signaling molecule genes which have positive or negative correlations between humans and Pfs. These genes may change their expression patterns to accommodate the respective organisms to mutually conflicting environments. Furthermore, it was possible to utilize the RNA-Seq data for genotyping of the parasites to identify possible drug resistant genetic variations. By bypassing technical difficulty in preparing samples in field, this approach should provide a practically useful mean to describe mutually interacting transcritpomes of humans and parasites, which should eventually explain diverse malaria symptoms.