Semantics and Services enabled Problem Solving Environment for Trypanosoma cruzi

描述（由申请人提供）：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建议的生物学应用。大约有1800万人（主要在拉丁美洲）感染了克氏锥虫。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，克氏锥虫的研究是一项重要的与人类疾病相关的工作。随着世界各地实验室产生的大量实验数据，它已经到了一个关键时刻，这在很大程度上要归功于2005年T.cruzi基因组的发表。虽然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异构数据库中，集成和可访问性差。本研究计划的科学目标是为T.cruzi开发和部署一个新的本体驱动的语义问题解决环境（PSE）。这是与国家生物医学本体中心（NCBO）合作，并将利用其资源来实现本提案的目标，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允许本地和公共数据的动态集成，以回答多个粒度级别的生物学问题。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，它还具有一套直观、全面的界面，便于生物学家使用和使用。多模态数据集将包括基因组数据和相关的生物信息学预测，代谢途径的功能信息，质谱和微阵列实验的实验数据，以及Pubmed的文本信息。研究人员将能够使用并为严格管理的T.cruzi知识库做出贡献，这将使其可重用和可扩展。作为该提案的一部分开发的资源也将对克氏锥虫相关的着丝质体、布氏锥虫和利什曼原虫（以及其他致病生物）的研究人员有用，这些研究使用类似的研究方案并面临类似的信息学挑战。公共卫生相关性：本提案的科学目标是为克氏锥虫开发和部署一种新的本体驱动的语义问题解决环境（PSE），克氏锥虫是一种寄生虫，感染了大约1800万人，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，以确定疫苗、诊断和治疗靶点，是一项重要的人类疾病相关努力。

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.