Transcriptional profiling of growth perturbations of the human malaria parasite Plasmodium falciparum
Transcriptional profiling of growth perturbations of the human malaria parasite Plasmodium falciparum
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DOI：
10.1038/nbt.1597
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发表时间：
2010-01-10
影响因子：
46.9
通讯作者：
Bozdech, Zbynek
中科院分区：
文献类型：
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作者：
Hu, Guangan;Cabrera, Ana;Bozdech, Zbynek
恶性疟原虫是导致最严重的人类疟疾的病原体，其大部分基因的功能尚未确定。在此，我们报告了 20 种抑制红细胞内发育周期裂殖期生长的化合物诱导的恶性疟原虫基因表达的变化。之前的研究报告了对化学诱导的恶性疟原虫生长扰动的反应仅发生了微小的变化，与此相反，我们发现，大约 59% 的编码基因在对我们测试的至少一种化学物质的反应中表现出超过三倍的表达变化。我们使用这个纲要来通过基因共表达、序列同源性、域-域和酵母双杂交数据构建的相互作用网络来进行蛋白质功能的关联预测。与裂殖子入侵相关的 42 种蛋白质中有 31 种的亚细胞定位与其在此过程中的作用一致，而这一过程是疟疾控制的关键目标。我们的网络可以促进新型抗疟药物和疫苗的鉴定。
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 similar to 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.