A Genomic Approach to Parasites From the Phylum Nematoda

描述（由申请人提供）： 寄生线虫感染超过一半的世界人口，导致显著的发病率和死亡率。线虫基因组的表征提供了关于这些寄生虫的基本分子信息，加速了基础研究以及有效诊断、疫苗和新药的开发。完成C.在对线虫基因组测序的基础上，华盛顿大学的基因组测序中心（GSC）已经生成并立即公开了来自25种线虫的超过210，000个表达序列标签（EST），包括所有主要人类寄生虫群体的代表，如钩虫、蠕虫、鞭虫和蛔虫。本申请旨在通过三个目标扩展可用的寄生线虫序列数据并提高其对研究界的价值。首先，我们将从寄生线虫中产生125，000个新序列，而每次读取的成本不到我们最初1999年提案的一半。测序工作将集中在流行的人类和动物土蠕虫蛔虫和钩虫的标准化文库上，这些蠕虫共同感染了超过20亿人，目标是识别每个物种中超过一半的基因。蛔虫微阵列将被制作并用于检查胚胎发育和成体器官中基因表达的差异。其次，我们将使用nematode.net和wormbase.org为寄生虫学社区提供用户友好、集成和持久的生物信息学数据库和工具。待创建或扩展的特征包括从所有可用的线虫序列数据组装的NemaGene簇共有序列、线虫肽序列的NemPep数据库、Gene Ontology和Interpro蛋白结构域分类以及密码子使用表。除了寄生虫学家的使用，这些信息的可用性将提供重要的进化背景的发展和遗传研究的模式C。优雅第三，我们将通过鉴定线虫特异性蛋白质结构域来研究线虫生物学的新领域，这些蛋白质结构域目前功能未知。NemaGene序列中缺乏Interpro结构域覆盖的区域将通过氨基酸序列进行聚类和比对，以创建新的候选结构域，目标是生成250个新的高质量结构域模型，以提交给Pfam/Interpro。与合作者合作，有限数量的新结构域将被更详细地描述，重点是假设分子或细胞功能。

DESCRIPTION (provided by applicant): Parasitic nematodes infect over half the world's population, resulting in significant morbidity and mortality. Characterization of nematode genomes provides fundamental molecular information about these parasites accelerating both basic research as well as the development of effective diagnostics, vaccines, and new drugs. After completing the C. elegans genome, Washington University's Genome Sequencing Center (GSC) has generated and immediately made public over 210,000 expressed sequence tags (ESTs) from 25 nematode species, including representatives of all the major groups of human parasites such as hookworms, filarial worms, whipworms, and Ascarids. This application seeks to extend the available parasitic nematode sequence data and enhance its value to the research community through three aims. First, we will generate 125,000 new sequences from parasitic nematodes for less than half the cost per read of our original 1999 proposal. Sequencing efforts will focus on normalized libraries from the prevalent human and animal geohelminths Ascaris and hookworm that together infect over 2 billion people with the goal of identifying over half of the genes in each species. An Ascaris microarray will be produced and used to examine differences in gene expression over embryogenesis and in adult organs. Second, we will use nematode.net and wormbase.org to provide the parasitology community with bioinformatics databases and tools that are user-friendly, integrated, and lasting. Features to be created or expanded include the NemaGene cluster consensus sequences assembled from all available nematode sequence data, the NemPep database of nematode peptide sequences, Gene Ontology and Interpro protein domain classifications, and codon usage tables. In addition to its use by parasitologists, the availability of such information will provide important evolutionary context to developmental and genetic studies in the model C. elegans. Third, we will investigate novel areas of nematode biology by identifying nematode-specific protein domains with currently unknown functions. Regions of NemaGene sequences lacking Interpro domain coverage will be clustered and aligned by amino acid sequence to create new candidate domains with the goal of generating 250 novel high quality domain models for submission to Pfam/Interpro. Working with collaborators, a limited number of novel domains will be characterized in more detail with an emphasis on postulating molecular or cellular function.