COMPARATIVE GENOMICS OF PARASITIC NEMATODES

描述（由申请人提供）：寄生线虫感染了世界上一半以上的人口，导致了显著的发病率和死亡率。线虫基因组的特征提供了关于这些寄生虫的基本分子信息，加速了新的诊断和治疗方法的基础研究和开发。华盛顿大学基因组中心已经生成并公开了来自30种寄生物种的40多万个cdna，对4个基因组进行了测序，并绘制了另外10个基因组的覆盖范围，其中包括主要人类寄生群体的代表。本提案的三个目的是分析扩展的线虫序列，以大大提高对寄生线虫生物学和细胞途径的理解。首先，我们将开发和使用生物信息学工具来处理、组装和注释来自所有测序平台的传入数据。这些基因组资源也将通过集中的寄生线虫数据库Nematode.net向更广泛的研究界传播。其次，分析将集中在保守和/或分类限制的生化途径上，包括可能被证明是有用的药物靶点的蛋白质。第三，我们将研究线虫在环境信息处理和内分泌系统中特异性蛋白质的插入和缺失的性质和意义。预期的结果将促进和促进新的干预措施的发现和发展，以控制这些重要的寄生虫并降低其相关的发病率和死亡率。

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 basic research and development of new diagnostics and therapeutics. Washington University's Genome Center has generated and made public over 400,000 cDNAs from 30 parasitic species, sequenced 4 genomes to draft coverage with ten more underway including representatives of the major human parasitic groups. The three aims in this proposal analyze the expanding nematode sequences to substantially improve understanding of parasitic nematode biology and cellular pathways. First, we will develop and use bioinformatic tools to process, assemble, and annotate incoming data from all sequencing platforms. These genomic resources will also be disseminated to the wider research community through the centralized parasitic nematode database, Nematode.net. Second, analysis will focus on biochemical pathways conserved and/or taxonomically restricted including proteins that may prove useful as drug targets. Third, we will study the nature and implications of nematode-specific insertions and deletions in proteins involved in environmental information processing and endocrine system. The expected outcome will facilitate and promote the discovery and development of novel interventions to control these important parasites and reduced their associated morbidity and mortality. PUBLIC HEALTH RELEVANCE: The continued development of molecular information, bioinformatics tools, and reagents for the study of parasitic nematodes is crucial, as they infect over half of the world's population and are a leading cause of human morbidity. The main goal of this project is to implement comparative genomics approaches to study the biology and cellular pathways of these important parasites, which on a long run will contribute to improved diagnostics, vaccines, and anthelmintic drugs for broad parasite control.