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Tools for Ontology Annotation: dcGO

本体标注工具：dcGO

基本信息

批准号：
BB/L018543/1
负责人：
Julian Gough
金额：
$ 10.07万
依托单位：
University of Bristol
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2014
资助国家：
英国
起止时间：
2014 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FL018543%2F1
关键词：
Tools Ontology Annotation dcGO

项目摘要

The massive amount of biological data, especially sequenced genomes and their end-product protein sequences, poses a prohibitive challenge for humans to manually cross-reference in literature. The solution is to use ontologies - controlled vocabularies - so that computer systems can process and connect rational relationships that are also readable by humans. The most used ontology is Gene Ontology (GO) that intends to describe protein functions.The most used resource for GO is UniProt. It provides protein sequence and functional annotation. GO annotations for proteins have two main types of evidence: one from experimental or curated annotations, the other from IEA (Inferred Electronic Annotations). IEA comes mostly from an InterPro mapping. InterPro is an integrated database that combines protein domains (or precisely signatures) from diverse sources with different definitions. In InterPro, annotations for domains are hand-curated via homology. Recently, we have pioneered a methodology in pursuit of a fully-automated tool: domain-centric Gene Ontology (dcGO). dcGO is the only freely available fully-automated general methodology for domain-based GO annotation. Thanks to its automated nature, dcGO is much more extensive than the InterPro hand curation. By comparison, we have shown that the quality of dcGO is at least as good as InterPro in terms of function predictions of proteins in UniProt. Therefore, extending dcGO to InterPro will have a considerable downstream impact on the UniProt IEA coverage and quality which is what scientists from around the world are routinely using as their primary source of annotation. In addition to GO, we will also provide domain annotations using other biomedical ontologies such as those describing diseases and phenotypes. For these kinds of annotations, currently only the dcGO approach can be extended in this way in a straightforward manner. In CAFA, a community-based critical assessment of protein function prediction, dcGO has been demonstrated for use in automated function annotation. In the next CAFA, we will prove that dcGO is also the suitable baseline for other ontologies and thus for inclusion in InterPro and UniProt. To meet the user requests for analysing sequences as a whole, we will also provide ontology enrichment analysis that will allow the users to understand which functions (and other relevant knowledge) are overrepresented in sequences submitted. This user-driven tool will be implemented in a computationally efficient way; the required will be on the order of seconds or minutes, rather than hours or days. In summary, the proposed research will be undertaken with a tight link to InterProt, UniProt, CAFA and end-users, and these collaborative connections will help translate our domain-centric solution into the industry standard for annotating and analyzing genome sequences.

海量的生物数据，特别是测序的基因组及其最终产物蛋白质序列，给人类在文献中手动交叉参考带来了令人望而却步的挑战。解决方案是使用本体论控制的词汇，这样计算机系统就可以处理和连接人类也可以阅读的理性关系。目前最常用的本体是描述蛋白质功能的基因本体(GO)，而GO最常用的资源是UniProt。它提供了蛋白质序列和功能注释。蛋白质的GO注释有两种主要类型的证据：一种来自实验或策划的注释，另一种来自IEA(推断电子注释)。IEA主要来自InterPro的映射。InterPro是一个集成的数据库，它结合了来自不同来源的具有不同定义的蛋白质结构域(或准确地说是签名)。在InterPro中，域的注释是通过同源手动管理的。最近，我们开创了一种方法论，追求一种全自动化的工具：以领域为中心的基因本体论(DcGO)。DcGO是唯一免费提供的基于域的围棋注释的全自动通用方法。由于其自动化的性质，dcGO比InterPro的手部管理要广泛得多。通过比较，我们已经表明，在UniProt中蛋白质的功能预测方面，dcGO的质量至少与InterPro一样好。因此，将dcGO扩展到InterPro将对UniProt IEA的覆盖范围和质量产生相当大的下游影响，而这正是来自世界各地的科学家经常使用的主要注释来源。除了围棋，我们还将使用其他生物医学本体提供领域注释，例如那些描述疾病和表型的本体。对于这些类型的注释，目前只有dcGO方法可以以这种直接的方式进行扩展。在CAFA中，一个基于社区的蛋白质功能预测的关键评估dcGO已经被证明用于自动功能注释。在下一届CAFA中，我们将证明dcGO也是其他本体的合适基线，从而可以包含在InterPro和UniProt中。为了满足用户对整体序列分析的要求，我们还将提供本体丰富分析，让用户了解哪些功能(和其他相关知识)在提交的序列中被过度表达。这个用户驱动的工具将以计算高效的方式实施；所需的时间将在几秒钟或几分钟的数量级上，而不是几小时或几天。总之，拟议的研究将与InterProt、UniProt、CAFA和最终用户紧密联系在一起，这些合作联系将有助于将我们以领域为中心的解决方案转化为注释和分析基因组序列的行业标准。