Interactive transcriptome analysis of malaria patients and infecting Plasmodium falciparum
- Junya Yamagishi1,2,
- Anna Natori3,
- Mohammed E.M. Tolba4,
- Arthur E. Mongan5,
- Chihiro Sugimoto6,
- Toshiaki Katayama7,
- Shuichi Kawashima7,
- Wojciech Makalowski8,
- Ryuichiro Maeda2,
- Yuki Eshita9,
- Josef Tuda5 and
- Yutaka Suzuki3
- 1Tohoku Medical Megabank Organization, Tohoku University, Sendai, Miyagi 980-8579, Japan;
- 2Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan;
- 3Department of Medical Genome Sciences, University of Tokyo, Kashiwa, Chiba 277-8562, Japan;
- 4Department of Parasitology, Assiut University, Assiut, 71515, Egypt;
- 5Department of Medicine, Sam Ratulangi University, Kampus Unsrat, Bahu Manado, 95115, Indonesia;
- 6Research Center for Zoonosis Control, Hokkaido University, Sapporo 001-0020, Japan;
- 7Database Center for Life Science (DBCLS), Research Organization of Information and Systems (ROIS), The University of Tokyo Bunkyo-ku, Tokyo 113-0032, Japan;
- 8Institute of Bioinformatics, Faculty of Medicine, University of Muenster, 48149 Munster, Germany;
- 9Oita University, School of Medicine, Yufushi, Oita 879-5593, Japan
- Corresponding author: ysuzuki{at}hgc.jp
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.
Footnotes
-
[Supplemental material is available for this article.]
-
Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.158980.113.
- Received April 14, 2013.
- Accepted May 20, 2014.
This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
