From the Institute of Cardiovascular Science (R.C.L., V.K.K., R.E.F., N.H.C., R.P.H., P.J.T., P.D.L., P.M.E., L.C.) and Metabolism and Experimental Therapeutics, Division of Medicine (R.B.), University College London, United Kingdom; European Bioinformatics Institute (EMBL-EBI), European Molecular Biology Laboratory, Hinxton, United Kingdom (P.R., D.O.-S.); Gene Ontology Consortium (P.R., T.Z.B., D.O.-S., J.A.B., D.P.H.); The Zebrafish Model Organism Database, University of Oregon, Eugene (D.G.H.); Rat Genome Database, Human Molecular Genetics Center, Medical College of Wisconsin, Milwaukee (S.J.F.L.); Arabidopsis Information Resource, Phoenix Bioinformatics, Fremont, CA (T.Z.B.); FlyBase, University of Cambridge, United Kingdom (S.T.); Mouse Genome Informatics, The Jackson Laboratory, Bar Harbor, ME (J.A.B., D.P.H.); Oxbridge BHF Centre of Regenerative Medicine, Department of Physiology, Anatomy and Genetics, University of Oxford, United Kingdom (P.R.R.); and William Harvey Heart Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, United Kingdom (A.T.).
Circ Genom Precis Med. 2018 Feb;11(2):e001813. doi: 10.1161/CIRCGEN.117.001813.
A systems biology approach to cardiac physiology requires a comprehensive representation of how coordinated processes operate in the heart, as well as the ability to interpret relevant transcriptomic and proteomic experiments. The Gene Ontology (GO) Consortium provides structured, controlled vocabularies of biological terms that can be used to summarize and analyze functional knowledge for gene products.
In this study, we created a computational resource to facilitate genetic studies of cardiac physiology by integrating literature curation with attention to an improved and expanded ontological representation of heart processes in the Gene Ontology. As a result, the Gene Ontology now contains terms that comprehensively describe the roles of proteins in cardiac muscle cell action potential, electrical coupling, and the transmission of the electrical impulse from the sinoatrial node to the ventricles. Evaluating the effectiveness of this approach to inform data analysis demonstrated that Gene Ontology annotations, analyzed within an expanded ontological context of heart processes, can help to identify candidate genes associated with arrhythmic disease risk loci.
We determined that a combination of curation and ontology development for heart-specific genes and processes supports the identification and downstream analysis of genes responsible for the spread of the cardiac action potential through the heart. Annotating these genes and processes in a structured format facilitates data analysis and supports effective retrieval of gene-centric information about cardiac defects.
系统生物学方法研究心脏生理学需要全面描述协调过程在心脏中的运作方式，以及能够解释相关转录组和蛋白质组实验的能力。基因本体论 (GO) 联盟提供了生物术语的结构化、受控词汇表，可用于总结和分析基因产物的功能知识。
在这项研究中，我们创建了一个计算资源，通过将文献注释与对 Gene Ontology 中心脏过程的改进和扩展的本体论表示的关注相结合，促进心脏生理学的遗传研究。结果，Gene Ontology 现在包含了全面描述心肌细胞动作电位、电偶联和窦房结到心室电脉冲传输中蛋白质作用的术语。评估这种方法对数据分析的有效性表明，在扩展的心脏过程本体论上下文中分析的 Gene Ontology 注释可以帮助识别与心律失常疾病风险位点相关的候选基因。
我们确定，心脏特异性基因和过程的注释和本体论开发的结合支持识别和下游分析负责心脏动作电位传播的基因。以结构化格式注释这些基因和过程有助于数据分析，并支持有效检索有关心脏缺陷的以基因为中心的信息。
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