Use of the protein ontology for multi-faceted analysis of biological processes: a case study of the spindle checkpoint.

Use of the protein ontology for multi-faceted analysis of biological processes: a case study of the spindle checkpoint.
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DOI:
10.3389/fgene.2013.00062
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发表时间:
2013
影响因子:
3.7
通讯作者:
Wu CH
Wu CH
中科院分区:
生物学3区
文献类型:
--
作者:
Ross KE;Arighi CN;Ren J;Natale DA;Huang H;Wu CH

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作为开放生物医学本体(OBO)的一员,蛋白质本体(PRO)提供了蛋白质形式和复合物及其关系的本体表示。PRO中的注释可以分配给单个蛋白质形式和复合物,每个都可以区分到翻译后修饰的水平,从而允许更精确地描述蛋白质功能,而不是将基因作为一个整体进行注释。此外,PRO与其他OBO本体完全可互操作,并集成了其他以蛋白质为中心的资源(如UniProt和Reactome)的知识。在这里,我们展示了PRO框架在纺锤体检查点研究中的价值,纺锤体检查点是一个高度保守的生物过程,广泛依赖于蛋白质修饰和蛋白质复合物的形成。纺锤体检查点通过监测染色体与纺锤体微管的附着和延缓细胞周期进程直至纺锤体完全组装来维持基因组的完整性。利用PRO和其他生物信息学工具,我们探索了纺锤体检查点蛋白的跨物种保护,包括磷酸化形式和复合物;研究磷酸化对纺锤体检查点功能的影响;并研究了纺锤体检查点蛋白与着丝点的相互作用,着丝点是检查点激活的部位。我们的方法可以推广到任何感兴趣的生物过程。
As a member of the Open Biomedical Ontologies (OBO) foundry, the Protein Ontology (PRO) provides an ontological representation of protein forms and complexes and their relationships. Annotations in PRO can be assigned to individual protein forms and complexes, each distinguishable down to the level of post-translational modification, thereby allowing for a more precise depiction of protein function than is possible with annotations to the gene as a whole. Moreover, PRO is fully interoperable with other OBO ontologies and integrates knowledge from other protein-centric resources such as UniProt and Reactome. Here we demonstrate the value of the PRO framework in the investigation of the spindle checkpoint, a highly conserved biological process that relies extensively on protein modification and protein complex formation. The spindle checkpoint maintains genomic integrity by monitoring the attachment of chromosomes to spindle microtubules and delaying cell cycle progression until the spindle is fully assembled. Using PRO in conjunction with other bioinformatics tools, we explored the cross-species conservation of spindle checkpoint proteins, including phosphorylated forms and complexes; studied the impact of phosphorylation on spindle checkpoint function; and examined the interactions of spindle checkpoint proteins with the kinetochore, the site of checkpoint activation. Our approach can be generalized to any biological process of interest.
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