title: Interactive transcriptome analysis of malaria patients and infecting Plasmodium falciparum.
abstract: To understand the molecular mechanisms of parasitism in vivo, it is essential to elucidate how the transcriptomes of the human hosts and the infecting parasites affect one another. Here we report the RNA-seq analysis of 116 Indonesian patients infected with the malaria parasite Plasmodium falciparum (Pf). We extracted RNAs from their peripheral blood as a mixture of host and parasite transcripts and mapped the RNA-seq tags to the human and Pf reference genomes to separate the respective tags. We were thus able to simultaneously analyze expression patterns in both humans and parasites. We identified human and parasite genes and pathways that correlated with various clinical data, which may serve as primary targets for drug developments. Of particular importance, we revealed characteristic expression changes in the human innate immune response pathway genes including TLR2 and TICAM2 that correlated with the severity of the malaria infection. We also found a group of transcription regulatory factors, JUND, for example, and signaling molecules, TNFAIP3, for example, that were strongly correlated in the expression patterns of humans and parasites. We also identified several genetic variations in important anti-malaria drug resistance-related genes. Furthermore, we identified the genetic variations which are potentially associated with severe malaria symptoms both in humans and parasites. The newly generated data should collectively lay a unique foundation for understanding variable behaviors of the field malaria parasites, which are far more complex than those observed under laboratory conditions.
authors.affiliation: Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi 980-8579, Japan; Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan;
authors.forename: Junya
authors.initials: J
authors.lastname: Yamagishi
authors.affiliation: Department of Medical Genome Sciences, University of Tokyo, Kashiwa, Chiba 277-8562, Japan;
authors.forename: Anna
authors.initials: A
authors.lastname: Natori
authors.affiliation: Department of Parasitology, Assiut University, Assiut, 71515, Egypt;
authors.forename: Mohammed E M
authors.initials: ME
authors.lastname: Tolba
authors.affiliation: Department of Medicine, Sam Ratulangi University, Kampus Unsrat, Bahu Manado, 95115, Indonesia;
authors.forename: Arthur E
authors.initials: AE
authors.lastname: Mongan
authors.affiliation: Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan;
authors.forename: Chihiro
authors.initials: C
authors.lastname: Sugimoto
authors.affiliation: Database Center for Life Science (DBCLS), Research Organization of Information and Systems (ROIS), The University of Tokyo Bunkyo-ku, Tokyo 113-0032, Japan;
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Katayama
authors.affiliation: Database Center for Life Science (DBCLS), Research Organization of Information and Systems (ROIS), The University of Tokyo Bunkyo-ku, Tokyo 113-0032, Japan;
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kawashima
authors.affiliation: Institute of Bioinformatics, Faculty of Medicine, University of Muenster, 48149 Munster, Germany;
authors.forename: Wojciech
authors.initials: W
authors.lastname: Makalowski
authors.affiliation: Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan;
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Maeda
authors.affiliation: Oita University, School of Medicine, Yufushi, Oita 879-5593, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Eshita
authors.affiliation: Department of Medicine, Sam Ratulangi University, Kampus Unsrat, Bahu Manado, 95115, Indonesia;
authors.forename: Josef
authors.initials: J
authors.lastname: Tuda
authors.affiliation: Department of Medical Genome Sciences, University of Tokyo, Kashiwa, Chiba 277-8562, Japan; ysuzuki@hgc.jp.
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Suzuki
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000962:Antimalarials / Q000627:therapeutic use; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004351:Drug Resistance / Q000235:genetics; D020224:Expressed Sequence Tags; D005260:Female; D015894:Genome, Human; D018503:Genome, Protozoan; D006790:Host-Parasite Interactions / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008288:Malaria / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010963:Plasmodium falciparum / Q000235:genetics* / Q000472:pathogenicity; D020641:Polymorphism, Single Nucleotide; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D014774:Virulence / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000962:Antimalarials; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C559371:JunD protein, human; D009687:Nuclear Proteins; D016755:Proto-Oncogene Proteins c-jun; C480228:TICAM2 protein, human; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
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