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富亮氨酸重复激酶2(LRRK2)相互作用组的可视化综述:利用深度整理的分子相互作用数据来呈现生物学过程

A visual review of the interactome of LRRK2: Using deep-curated molecular interaction data to represent biology.

作者信息

Porras Pablo, Duesbury Margaret, Fabregat Antonio, Ueffing Marius, Orchard Sandra, Gloeckner Christian Johannes, Hermjakob Henning

机构信息

European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, UK.

出版信息

Proteomics. 2015 Apr;15(8):1390-404. doi: 10.1002/pmic.201400390. Epub 2015 Mar 21.

Abstract

Molecular interaction databases are essential resources that enable access to a wealth of information on associations between proteins and other biomolecules. Network graphs generated from these data provide an understanding of the relationships between different proteins in the cell, and network analysis has become a widespread tool supporting -omics analysis. Meaningfully representing this information remains far from trivial and different databases strive to provide users with detailed records capturing the experimental details behind each piece of interaction evidence. A targeted curation approach is necessary to transfer published data generated by primarily low-throughput techniques into interaction databases. In this review we present an example highlighting the value of both targeted curation and the subsequent effective visualization of detailed features of manually curated interaction information. We have curated interactions involving LRRK2, a protein of largely unknown function linked to familial forms of Parkinson's disease, and hosted the data in the IntAct database. This LRRK2-specific dataset was then used to produce different visualization examples highlighting different aspects of the data: the level of confidence in the interaction based on orthogonal evidence, those interactions found under close-to-native conditions, and the enzyme-substrate relationships in different in vitro enzymatic assays. Finally, pathway annotation taken from the Reactome database was overlaid on top of interaction networks to bring biological functional context to interaction maps.

摘要

分子相互作用数据库是重要的资源,可让人获取有关蛋白质与其他生物分子之间关联的大量信息。从这些数据生成的网络图有助于理解细胞中不同蛋白质之间的关系,并且网络分析已成为支持组学分析的广泛应用的工具。有意义地呈现这些信息绝非易事,不同的数据库努力为用户提供详细记录,以捕捉每条相互作用证据背后的实验细节。需要一种有针对性的整理方法,将主要由低通量技术生成的已发表数据转移到相互作用数据库中。在本综述中,我们给出一个例子,突出有针对性的整理以及随后对人工整理的相互作用信息详细特征进行有效可视化的价值。我们整理了涉及LRRK2的相互作用,LRRK2是一种功能 largely unknown 且与家族性帕金森病相关的蛋白质,并将数据存放在IntAct数据库中。然后,这个特定于LRRK2的数据集被用于生成不同的可视化示例,突出数据的不同方面:基于正交证据的相互作用置信水平、在接近天然条件下发现的那些相互作用,以及不同体外酶促试验中的酶 - 底物关系。最后,从Reactome数据库获取的通路注释被叠加在相互作用网络之上,为相互作用图谱赋予生物学功能背景。 (注:原文中“largely unknown”直译为“很大程度上未知”,这里为了更通顺表述为“功能 largely unknown” )

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd16/4415485/f22ef3150483/pmic0015-1390-f1.jpg

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