Experimental Annotation of the P. Falciparum Genome

描述（由申请人提供）：疟疾是全球发病率和死亡率很高的原因。其基因组序列的完成有望通过产生大量新靶点来加速开发这种使人衰弱的疾病的新疗法的过程。然而，在基因组测序计划中鉴定的蛋白质中，只有35%具有假定的功能，甚至更小的百分比（<13%）有直接的实验证据支持其功能分配。鉴于疟疾是一种遗传学困难的细胞内寄生虫，如果使用常规方法确定功能，这些数字在未来不太可能发生重大变化。然而，使用新的高通量技术，如全球基因表达监测，可以经济有效地将功能信息添加到恶性疟原虫基因组中。然而，在实现这一目标之前，重要的是确定其产物相互作用并具有相似功能作用的基因在恶性疟原虫中是否具有共同的基因表达谱。为了验证这一点，我们将检查大量恶性疟原虫阶段的基因表达谱，并询问在同一时间和同一地点表达的基因是否具有相似的功能。 为了实验验证，我们将集中在一组基因的表达模式表明，他们可能参与重组的红细胞骨架在环阶段的寄生虫。作为本研究的副产品，将确认参与宿主寄生虫相互作用的新基因，并创建转录图谱，显示每个基因在生命周期的所有可访问阶段的表达时间和水平。这些数据还应该有助于基因组的实验注释，允许重新评估基因模型，并为其他对寄生虫基因组数据挖掘感兴趣的人提供丰富的材料来源。这里描述的基本基因组学方法应该作为模型，用于确定基因功能在其他寄生虫与困难的遗传学。

DESCRIPTION (provided by applicant): Malaria is the cause of significant global morbidity and mortality. The completion of its genome sequence promises to accelerate the process of developing new treatments for this debilitating disease by yielding a wealth of new targets. However, only 35% of the proteins identified in the genome sequencing project have a presumed function and an even smaller percentage (<13%) have direct experimental evidence supporting their functional assignment. Given that malaria is an intracellular parasite with difficult genetics, these numbers are unlikely to change significantly in the future if conventional methods are used for determining function. However, functional information could cost-effectively be added to the P. falciparum genome using new high-throughput technologies, such as global gene expression-monitoring. However, before such a goal can be realized it will be important to determine whether or not genes whose products interact with one another and have similar functional roles have common gene expression profiles in P. falciparum. To test this we will examine gene expression profiles from a large number of P. falciparum stages and ask whether or not genes expressed at the same time and at the same place have similar functions. For experimental validation we will concentrate on a group of genes whose expression pattern suggests they may be involved in the reorganization of the erythrocyte cytoskeleton in ring-stage parasites. As a by product of this investigation, new genes involved in host parasite interactions will be confirmed and a transcriptional map will be created showing when and to what level each gene is expressed for all accessible stages of the lifecycle. The data should also aid in the experimental annotation of the genome, allow gene models to be re-evaluated and serve as a rich source of material for others interested in data-mining the parasite genome. The basic genomic methods described here should serve as models for determining gene function in other parasites with difficult genetics.