Ontology-based multiscale investigation of human neurological disease models

描述(由申请人提供)：阅读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，其中一些相互矛盾，关于这种疾病的已知病理特征和临床特征之间的相关性。为了帮助解开帕金森障碍和脑缺血等疾病的多方面维度，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，并提供一种更严格的方法来比较模型系统和人类疾病。国家生物医学本体论中心(NCBO)、国家显微镜和成像研究中心以及生物医学信息学研究网络项目之间的合作将开发在本体论、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努力开发表型和特征本体以机器可处理的形式表达复杂表型的基础上，以便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。将开发用于注释帕金森障碍和短暂性脑缺血动物模型的复杂特征的本体，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的表型关联的手段。该项目形成了NCBO的一个推动生物学项目，将对多个空间和时间尺度的基于本体的分析的需要纳入到NCBO正在开发的框架中，同时向NCBO管理的开放生物本体和数据储存库提供本体和数据。该提案的一个核心组成部分是开发一个基于本体论的综合环境，以帮助科学家了解观察数据和收集的关于帕金森氏症等神经疾病的知识之间的深层相互关系。因此，拟议的工作直接与NCBO的既定目标保持一致：创建、访问和浏览相关的本体；使用本体来注释实验数据集；访问注释的数据并从注释的数据中得出推论；以及在模型系统和人类疾病之间架起桥梁。尽管作为本提案一部分开发的工具将在特定的驾驶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