Division of Genetics and Genomics, School of Biological Sciences, Nanyang Technological University, Singapore.
Nat Biotechnol. 2010 Jan;28(1):91-8. doi: 10.1038/nbt.1597. Epub 2009 Dec 27.
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 approximately 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.
疟原虫是引起人类疟疾的主要病原体，其大多数基因的功能尚未确定。在这里，我们报告了 20 种化合物对红内期裂殖体生长的抑制作用诱导的疟原虫基因表达的变化。与之前的研究相比，这些研究只报道了疟原虫生长受到化学诱导干扰时的最小变化，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达水平发生了三倍以上的变化。我们使用这个汇编，通过从基因共表达、序列同源性、结构域-结构域和酵母双杂交数据构建的相互作用网络，进行基于关联的蛋白功能预测。与裂殖子入侵相关的 42 个蛋白中的 31 个的亚细胞定位与其在该过程中的作用一致，这是疟疾控制的一个关键靶点。我们的网络可能有助于鉴定新的抗疟药物和疫苗。
