PRO: A Protein Ontology in OBO Foundry for Integration of Biomedical Knowledge

描述（由申请人提供）：生物医学本体是准确表示和整合生物医学和转化研究中基因组规模数据的关键工具。OBO（开放生物和生物医学本体论）铸造是一个社区的努力，在一套不断发展的最佳实践原则的基础上，为基于证据的本体论开发开发一个系统和协调的框架。蛋白质本体（PRO）是OBO铸造厂内蛋白质的参考本体，与基因本体一起，是铸造厂推荐的作为社区融合首选目标的前六个本体之一。为了提供一个基本的本体框架来获取系统生物学背景下的蛋白质知识，PRO包含三个子本体来表示(1)基于进化相关性的同源基因的蛋白质（ProEvo）；(2)由给定基因产生的蛋白质形式，包括剪接异构体、突变变体和共同或翻译后修饰形式（ProForm）；(3)含蛋白复合物（ProComp）。这项竞争性更新拨款申请旨在进一步发展PRO，以促进生物医学研究界对其语义和计算的使用，从而扩大其对健康科学发现和推理的科学影响。具体目标是：(i)加强PRO本体框架；（ii）扩大蛋白质对象的覆盖范围；（iii）改善展览平台、网站和视觉表现；（四）开展临床驱动项目；(v)扩大PRO的科学影响、采用和传播。本体论框架将捕获新的蛋白质对象和关系类型，并连接到语义资源和推理工具。PRO将通过映射和关系定义来扩大覆盖范围，以连接现有知识库中的蛋白质对象，并通过从精心策划的数据库中半自动导入蛋白质形式和复合物。在疾病建模的生物学背景下，图形网络表示将无缝连接蛋白质形式和复合物。用例和两个具体的驱动临床项目——一个用于阿尔茨海默病的推理和假设生成，一个用于流式细胞术数据表示和免疫系统建模——将展示知识集成在OBO Foundry框架中，作为健康科学推理和建模的支持研究基础设施。我们将举办年度PRO科学传播会议，以解决生物和临床信息学研究界的蛋白质相关需求。PRO将通过多个网站和本体服务，以及通过与主要知识资源的相互链接进行传播。蛋白质对象的ID管理将包括将PRO术语映射到具有良好定义关系的公共数据库标识符，并加速创建所请求的PRO术语和uid。PRO研究具有几个独特的特点，其意义是多方面的。对于知识表示，PRO定义了精确的蛋白质对象，以支持适当粒度的准确注释，并提供了本体框架，以连接建模生物学所需的所有蛋白质类型，特别是将特定的蛋白质形式连接到生物学背景下的特定复合物。对于语义数据集成，PRO提供了本体结构，通过指定的关系连接数据库中包含的大量蛋白质知识，以支持新的假设生成和测试。因此，PRO解决了目前蛋白质表示生物信息学基础设施中的空白，使计算推理更容易获得蛋白质知识，充分利用和补充现有的知识来源。拟议的研究将使PRO联盟能够汇集来自几个合作机构的资源和专业知识，以深化和扩大PRO作为生物医学知识发现和转化科学的成熟研究基础设施。

DESCRIPTION (provided by applicant): Biomedical ontologies are critical tools for the accurate representation and integration of genome-scale data in biomedical and translational research. The OBO (Open Biological and Biomedical Ontologies) Foundry is a community effort to develop a systematic and coordinated framework for evidence-based ontology development on the basis of an evolving set of best practice principles. The Protein Ontology (PRO) is the reference ontology for proteins within the OBO Foundry, and is, with the Gene Ontology, one of the first six ontologies recommended by the Foundry as preferred targets for community convergence. To provide a basic ontological framework to capture protein knowledge in a systems biology context, PRO encompasses three sub-ontologies to represent (1) proteins from homologous genes based on evolutionary relatedness (ProEvo); (2) protein forms produced from a given gene, including splice isoforms, mutation variants, and co- or post-translationally modified forms (ProForm); and (3) protein-containing complexes (ProComp). This competitive renewal grant application aims to further develop PRO in order to facilitate its semantic and computational use by the biomedical research community and thereby broaden its scientific impact for discovery and reasoning in the health sciences. The specific aims are: (i) to enhance the PRO ontological framework; (ii) to broaden the coverage of protein objects; (iii) to enhance the PRO curation platform, website and visual representation; (iv) to develop driving clinical projects; and (v) to expand the scientific impact, adoption and dissemination of PRO. The ontological framework will capture new types of protein objects and relations and connect to semantic resources and reasoning tools. PRO will broaden coverage through mappings and definitions of relations to connect protein objects in existing knowledge bases, and via semi-automated import of protein forms and complexes from curated databases. A graphical network representation will seamlessly connect protein forms and complexes across tax in biological context for disease modeling. Use cases and two specific Driving Clinical Projects-one for reasoning and hypothesis generation for Alzheimer's disease, and one for flow cytometry data representation and immune system modeling-will demonstrate knowledge integration in the OBO Foundry framework as an enabling research infrastructure for reasoning and modeling in the health sciences. We will host annual PRO Scientific Dissemination Meetings addressing the protein-related needs of the bio- and clinical informatics research communities. PRO will be disseminated via multiple websites and ontological services, as well as through reciprocal links with major knowledge resources. ID management for protein objects will include mapping of PRO terms to common database identifiers with well-defined relations and expedited creation of requested PRO terms and UIDs. The PRO research has several unique features and its significance is multi-fold. For knowledge representation, PRO defines precise protein objects to support accurate annotation at the appropriate granularity and provides the ontological framework to connect all protein types necessary to model biology, in particular linking specific protein forms to particular complexes in biological context. For semantic data integration, PRO provides the ontological structure to connect-via specified relations- the vast amounts of protein knowledge contained in databases to support new hypothesis generation and testing. PRO therefore addresses the current gaps in the bioinformatics infrastructure for protein representations in a way that makes knowledge about proteins more accessible to computational reasoning, fully leveraging and complementing existing knowledge sources. The proposed research will allow the PRO Consortium to bring together the resources and expertise from several collaborating institutions to deepen and broaden PRO as a mature research infrastructure for biomedical knowledge discovery and translational science.