PRO: A Protein Ontology in Open Biomedical Ontologies

描述(由申请人提供)：生物医学本体论在基因组和蛋白质组研究中越来越重要，在这些研究中，不同资源中的复杂数据需要整合。特别是，基因本体论(GO)已经成为基因组注释的标准，开放生物医学本体论(OBO)是跨生物医学领域共享本体论的保护伞。然而，目前的OBO文库存在一个空白--蛋白质类别及其关系的本体。该项目的目标是开发一个蛋白质本体论(PRO)，以促进蛋白质注释和功能发现。PRO将在OBO Foundry内开发，采用指定本体开发最佳实践的原则。这个项目的具体目标是：(I)开发蛋白质进化(ProEvo)本体，用于基于进化关系描述蛋白质；(Ii)开发蛋白质修饰形式(Promod)本体，用于表示基因的多种蛋白质形式；(Iii)明确PRO、GO和其他OBO本体之间的关系；以及(Iv)传播PRO本体并开发科学案例研究。ProEvo将基于PIRSF和Panther中人工挑选的全长蛋白质家族以及它们在SCOP和Pfam中的组成结构域进行开发，最初是为了人类含有蛋白质的类别。ProEvo类及其与GO术语的关系将形式化系统发育和功能之间的关系，以允许基于实验证据对功能进行更一致和准确的推断。Promod将定义由遗传变异、选择性剪接、蛋白水解性切割和翻译后修饰产生的蛋白质产品，最初使用UniProtKB/Swiss-Prot和小鼠基因组倡议中的完全精选条目为人类和小鼠蛋白质定义蛋白质产品，以支持在变体、异构体和修饰产品的精确水平上对蛋白质组进行特定注释。基于人类和小鼠疾病蛋白的科学案例研究定义的PRO、GO和其他OBO本体之间的关系，如疾病本体，将捕获疾病理解所需的关系。为了向社会传播，本体将被整合到OBO中，新的关系将被添加到OBO关系本体中，并将组织一年一度的蛋白质本体研讨会。PRO还可以从PIR网站访问，以进行综合蛋白质分析。通过科学会议和合作，PRO联盟将与更广泛的科学界互动，以确保PRO是有用的并被广泛采用。专业本体论将允许研究人员探索蛋白质的功能和进化关系，以提高对疾病的理解，并确定潜在的诊断和治疗目标。

DESCRIPTION (provided by applicant): Biomedical ontologies are increasingly important in genomic and proteomic research where complex data in disparate resources need to be integrated. In particular, the Gene Ontology (GO) has become a standard for genome annotation and the Open Biomedical Ontologies (OBO) is an umbrella for ontologies shared across biomedical domains. There is, however, a gap in the current OBO library-an ontology of protein classes and their relationships. The goal of the proposed project is to develop a PRotein Ontology (PRO) to facilitate protein annotation and functional discovery. PRO will be developed within the OBO Foundry, adopting principles specifying best practices in ontology development. The specific aims of this project are to: (i) develop a Protein Evolution (ProEvo) ontology for the description of proteins based on evolutionary relationships, (ii) develop an ontology for Protein Modified Forms (ProMod) for the representation of multiple protein forms of a gene, (iii) specify relationships between PRO, GO and other OBO ontologies, and (iv) disseminate PRO ontology and develop scientific case studies. ProEvo will be developed based on manually-curated families of full-length proteins in PIRSF and PANTHER and their constituent domains in SCOP and Pfam, initially for human protein-containing classes. The ProEvo classes and their relationships with GO terms will formalize the relationships between phytogeny and function, to allow more consistent and accurate inference of function based on experimental evidence. ProMod will define protein products generated by genetic variation, alternative splicing, proteolytic cleavage, and post-translational modification, initially for human and mouse proteins using fully-curated entries in UniProtKB/Swiss-Prot and the Mouse Genome Initiative, to support specific annotation of proteomes at the precise levels of variants, isoforms, and modified products. Defined based on scientific case studies of human and mouse disease proteins, the relations between PRO, GO, and other OBO ontologies, such as Disease Ontology, will capture the relationships required for disease understanding. For PRO .dissemination to the community, the ontology will be integrated into OBO, new relations will be added to the OBO Relations Ontology, and an annual protein ontology workshop will be organized. PRO will also be accessible from the PIR web site for integrative protein analysis. Through scientific meetings and collaborations, the PRO consortium will interact with the wider scientific community to ensure that PRO is useful and widely adopted. The PRO ontology will allow researchers to explore functional and evolutionary relationships of proteins to improve understanding of disease and identify potential diagnostic and therapeutic targets.