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恶性疟原虫有性发育转录组:基于本体模式识别的微阵列分析

The Plasmodium falciparum sexual development transcriptome: a microarray analysis using ontology-based pattern identification.

作者信息

Young Jason A, Fivelman Quinton L, Blair Peter L, de la Vega Patricia, Le Roch Karine G, Zhou Yingyao, Carucci Daniel J, Baker David A, Winzeler Elizabeth A

机构信息

Department of Cell Biology ICND202, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.

出版信息

Mol Biochem Parasitol. 2005 Sep;143(1):67-79. doi: 10.1016/j.molbiopara.2005.05.007.

Abstract

The sexual stages of malarial parasites are essential for the mosquito transmission of the disease and therefore are the focus of transmission-blocking drug and vaccine development. In order to better understand genes important to the sexual development process, the transcriptomes of high-purity stage I-V Plasmodium falciparum gametocytes were comprehensively profiled using a full-genome high-density oligonucleotide microarray. The interpretation of this transcriptional data was aided by applying a novel knowledge-based data-mining algorithm termed ontology-based pattern identification (OPI) using current information regarding known sexual stage genes as a guide. This analysis resulted in the identification of a sexual development cluster containing 246 genes, of which approximately 75% were hypothetical, exhibiting highly-correlated, gametocyte-specific expression patterns. Inspection of the upstream promoter regions of these 246 genes revealed putative cis-regulatory elements for sexual development transcriptional control mechanisms. Furthermore, OPI analysis was extended using current annotations provided by the Gene Ontology Consortium to identify 380 statistically significant clusters containing genes with expression patterns characteristic of various biological processes, cellular components, and molecular functions. Collectively, these results, available as part of a web-accessible OPI database (http://carrier.gnf.org/publications/Gametocyte), shed light on the components of molecular mechanisms underlying parasite sexual development and other areas of malarial parasite biology.

摘要

疟原虫的有性阶段对于疟疾通过蚊子传播至关重要,因此是传播阻断药物和疫苗研发的重点。为了更好地了解对有性发育过程重要的基因,利用全基因组高密度寡核苷酸微阵列对高纯度的I - V期恶性疟原虫配子体的转录组进行了全面分析。通过应用一种名为基于本体的模式识别(OPI)的新型基于知识的数据挖掘算法,并以关于已知有性阶段基因的当前信息为指导,辅助对该转录数据进行解读。该分析鉴定出一个包含246个基因的有性发育簇,其中约75%为假设基因,呈现高度相关的、配子体特异性的表达模式。对这246个基因的上游启动子区域进行检查,揭示了有性发育转录调控机制的假定顺式调控元件。此外,利用基因本体联合会提供的当前注释扩展了OPI分析,以鉴定出380个具有统计学意义的簇,这些簇包含具有各种生物学过程、细胞成分和分子功能特征表达模式的基因。这些结果作为一个可通过网络访问的OPI数据库(http://carrier.gnf.org/publications/Gametocyte)的一部分提供,共同揭示了寄生虫有性发育及疟原虫生物学其他领域潜在分子机制的组成部分。

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