Semantics and Services enabled Problem Solving Environment for Trypanosoma cruzi

描述(申请人提供)：对复杂生物系统的研究越来越依赖于来自不同来源的大量动态信息。对人类恰加斯病的主要病原体--克氏锥虫的科学分析是推动这一提议的生物学应用的动力。大约有1800万人感染了克氏锥虫，主要是在拉丁美洲。据预测，其中多达40%的人最终会患上恰加斯病，这是该地区中年人心脏病和猝死的主要原因。因此，对克氏毛滴虫的研究是一项与人类疾病相关的重要努力。随着世界各地实验室产生的大量实验数据已经到了关键时刻，这在很大程度上要归功于2005年克氏锥虫基因组的公布。尽管这项研究具有显著改善人类健康的潜力，但所产生的数据存在于独立的、不同种类的数据库中，集成性和可访问性较差。该研究方案的科学目标是开发和部署一个新的本体驱动的语义问题求解环境(PSE)。这是与国家生物医学本体论中心(NCBO)合作的，将利用其资源实现这项提议的目标，并有效地将结果传播给更广泛的生命科学界，包括人类病原体的研究人员。PSE允许动态集成本地和公共数据，以在多个粒度级别回答生物问题。PSE将利用最先进的语义技术对多个数据库进行有效查询，同样重要的是，它具有一套直观和全面的界面，便于生物学家使用和采用。多模式数据集中将包括基因组数据和相关的生物信息学预测，来自代谢途径的功能信息，来自质谱学和微阵列实验的实验数据，以及来自Pubmed的文本信息。研究人员将能够使用和贡献一个经过严格管理的T.ruzi知识库，使其可重复使用和扩展。作为这项提议的一部分开发的资源也将对克氏锥虫相关动体、布氏锥虫和大利什曼原虫(以及其他病原生物)的研究人员有用，这些研究人员使用类似的研究方案，面临类似的信息学挑战。与公共卫生相关：这项提议的科学目标是为克鲁兹锥虫开发和部署一个新的本体驱动的语义问题解决环境(PSE)，这是一种感染约1800万人的寄生虫，主要在拉丁美洲。预计多达40%的感染者最终会患上恰加斯病，这是该地区中年人心脏病和猝死的主要原因。通过PSE促进克氏锥虫研究，目的是确定疫苗、诊断和治疗目标，这是一项与人类疾病相关的重要努力。

DESCRIPTION (provided by applicant): The study of complex biological systems increasingly depends on vast amounts of dynamic information from diverse sources. The scientific analysis of the parasite Trypanosoma cruzi (T.cruzi), the principal causative agent of human Chagas disease, is the driving biological application of this proposal. Approximately 18 million people, predominantly in Latin America, are infected with the T.cruzi parasite. As many as 40 percent of these are predicted eventually to suffer from Chagas disease, which is the leading cause of heart disease and sudden death in middle-aged adults in the region. Research on T. cruzi is therefore an important human disease related effort. It has reached a critical juncture with the quantities of experimental data being generated by labs around the world, due in large part to the publication of the T.cruzi genome in 2005. Although this research has the potential to improve human health significantly, the data being generated exist in independent heterogeneous databases with poor integration and accessibility. The scientific objectives of this research proposal are to develop and deploy a novel ontology-driven semantic problem-solving environment (PSE) for T.cruzi. This is in collaboration with the National Center for Biomedical Ontologies (NCBO) and will leverage its resources to achieve the objectives of this proposal as well as effectively to disseminate results to the broader life science community, including researchers in human pathogens. The PSE allows the dynamic integration of local and public data to answer biological questions at multiple levels of granularity. The PSE will utilize state-of- the-art semantic technologies for effective querying of multiple databases and, just as important, feature an intuitive and comprehensive set of interfaces for usability and easy adoption by biologists. Included in the multimodal datasets will be the genomic data and the associated bioinformatics predictions, functional information from metabolic pathways, experimental data from mass spectrometry and microarray experiments, and textual information from Pubmed. Researchers will be able to use and contribute to a rigorously curated T.cruzi knowledge base that will make it reusable and extensible. The resources developed as part of this proposal will be also useful to researchers in T.cruzi related kinetoplastids, Trypanosoma brucei and Leishmania major (among other pathogenic organisms), which use similar research protocols and face similar informatics challenges. PUBLIC HEALTH RELEVANCE: The scientific objective of this proposal is to develop and deploy a novel ontology-driven semantic problem-solving environment (PSE) for Trypanosoma cruzi, a parasite that infects approximately 18 million people, predominantly in Latin America. As many as 40 percent of those infected are predicted to eventually suffer from Chagas disease, the leading cause of heart disease and sudden death in middle-aged adults in the region. Facilitating T.cruzi research through the PSE, with the aim of identifying vaccine, diagnostic, and therapeutic targets, is an important human disease related endeavor.