Ontology-based multiscale investigation of human neurological disease models

描述（由申请人提供）：阅读关于任何神经退行性疾病的文献，很快就会导致一系列令人困惑的事实，有些是相互矛盾的，关于疾病的已知病理和临床特征之间的相关性。为了帮助揭示帕金森病和脑缺血等疾病的多面性，我们描述了一个表示人类神经疾病和动物模型特征的正式系统，以促进对疾病机制的理解，并提供更严格的方法来比较模型系统和人类疾病。国家生物医学本体中心（NCBO）、国家显微镜与成像研究中心和生物医学信息学研究网络项目之间的合作将开发在本体、分布式数据库和图像中包含的信息之间架起桥梁的工具。这项工作建立在NCBO开发表型和性状本体的基础上，该本体用于以机器可处理的形式表达复杂表型，因此可以使用强大的算法来寻找数据中的相关性和有趣的模式。将开发用于帕金森病和短暂性脑缺血动物模型复杂特征注释的本体，并将其应用于多尺度成像数据的分析。这个本体论将提供执行基于本体论的图像分析和跨尺度表型的相关性的手段。该项目为NCBO形成了一个驱动型的生物学项目，将基于本体的多时空尺度分析需求引入NCBO正在开发的框架中，同时将本体和数据提供给NCBO管理的开放生物本体和数据存储库。该提案的一个核心组成部分是开发一个基于本体的集成环境，这将有助于科学家了解观察到的数据和收集到的关于神经系统疾病（如帕金森病）的知识之间的深层相互关系。因此，拟议的工作直接符合NCBO的既定目标：创建、访问和浏览相关本体；使用本体对实验数据集进行注释；访问并从注释数据中得出推论；是连接模型系统和人类疾病的桥梁。尽管作为本提案一部分开发的工具将在特定驱动生物学项目的背景下开发，但它们将广泛适用于其他成像

DESCRIPTION (provided by applicant): Reading the literature on any neurodegenerative condition quickly leads to a bewildering array of facts, some contradictory, regarding the correlations between known pathological and clinical features of the disease. To help unravel the multifaceted dimensions of diseases such as Parkinsonian disorders and cerebral ischemia, we describe a formal system for representing the characteristics of human neurological disease and animal models to promote understanding of disease mechanisms and to provide a more rigorous method to compare model systems and human disease. This collaboration between the National Center for Biomedical Ontologies (NCBO), the National Center for Microscopy and Imaging Research and the Biomedical Informatics Research Network project will develop tools that bridge between information contained in ontologies, distributed databases and images. This work builds upon efforts at NCBO to develop a Phenotype and Trait Ontology for expression of complex phenotypes in a machine-processable form, so that powerful algorithms can be employed to look for correlations and interesting patterns in the data. Ontologies for annotation of complex traits from animal models of Parkinsonian disorders and transient cerebral ischemia will be developed and applied to an analysis of multiscale imaging data. This ontology will provide the means to perform ontology-based image analysis and correlation of phenotypes across scales. This project forms a driving biological project for NCBO, bringing the need for ontology-based analysis of multiple spatial and temporal scales into the frameworks under development at NCBO, while at the same time contributing ontologies and data into the Open Biological Ontologies and Data repositories curated by NCBO. A core component of the proposal is the development of an integrated ontology-based environment for the that will help the scientist to understand the deep interrelationships among observed data and collected knowledge about neurological diseases such as Parkinson's. The proposed work thus aligns directly with the stated objectives of NCBO: create, access and browse relevant ontologies; use ontologies to annotate experimental datasets; access and draw inferences from the annotated data; and bridge between model systems and human disease. Eventhough tools developed as part of this proposal will be developed in the context of a specific driving biological project they will be broadly applicable to other imaging