Experimental Annotation of the P. Falciparum Genome

描述(申请人提供)：疟疾是导致全球重大发病率和死亡率的原因。其基因组序列的完成有望通过产生大量新的靶点，加快开发这种令人衰弱的疾病的新疗法的进程。然而，在基因组测序项目中只有35%的蛋白质具有推测的功能，更少的百分比(13%)有直接的实验证据支持它们的功能分配。鉴于疟疾是一种遗传困难的细胞内寄生虫，如果使用传统方法来确定功能，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，可以经济高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，确定其产物相互作用并具有相似功能的基因在恶性疟原虫中是否具有共同的基因表达谱将是重要的。为了测试这一点，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类似的功能。 为了进行实验验证，我们将集中在一组基因上，这些基因的表达模式表明它们可能参与了环期寄生虫红细胞细胞骨架的重组。作为这项研究的副产品，参与寄主寄生虫相互作用的新基因将得到确认，并将创建转录图谱，显示在生命周期的所有可访问阶段，每个基因表达的时间和水平。这些数据还应该有助于对基因组的实验性注释，允许重新评估基因模型，并为其他有兴趣对寄生虫基因组进行数据挖掘的人提供丰富的材料来源。这里描述的基本基因组方法应该作为确定其他具有困难遗传学的寄生虫的基因功能的模型。

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.