The commonality of protein interaction networks determined in neurodegenerative disorders (NDDs)
The commonality of protein interaction networks determined in neurodegenerative disorders (NDDs)
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DOI：
10.1093/bioinformatics/btm307
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发表时间：
2007-08-15
期刊：
影响因子：
5.8
通讯作者：
Kanehisa, Minoru
中科院分区：
文献类型：
--
作者：
Limviphuvadh, Vachiranee;Tanaka, Seigo;Kanehisa, Minoru
动机：神经退行性疾病（NDD）是一种进行性和致死性疾病，其特征通常是细胞内或细胞外存在异常蛋白质聚集体。鉴定和验证与致病基因产物相互作用的蛋白质是了解其生理和病理功能的有效途径。本研究的目的是利用蛋白质-蛋白质相互作用网络、NDD中常见的结构域特征以及基于结构域信息的NDD之间的相关性，更好地理解NDD中常见的分子致病机制。结果：通过查阅PubMed中的已发表文献，我们在京都基因和基因组百科全书（KEGG）中创建了6种NDD中蛋白质-蛋白质相互作用的通路图：阿尔茨海默病（AD）、帕金森病（PD）、肌萎缩侧索硬化（ALS）、亨廷顿病（HD）、齿状核红核-苍白球路易体萎缩（DRPLA）和朊病毒病（PRION）。我们还从文献中收集了201个相互作用蛋白质和13个具有282个相互作用的化合物的数据。我们发现这六种NDD共有19种蛋白质。这些蛋白主要参与细胞凋亡和MAPK信号通路。我们通过添加来自人类蛋白质参考数据库的蛋白质相互作用数据和来自人类基因表达指数数据库的基因表达数据来扩展相互作用网络。对扩展后的网络进行结构域分析，发现了常见蛋白质的特征结构域，如14-3-3蛋白、磷酸酪氨酸相互作用结构域和caspase结构域。此外，就蛋白质结构域分布而言，我们发现AD、PD、HD和PRION之间存在相对较高的相关性，而ALS或DRPLA则没有相关性。可用性：http://www.genome.jp/kegg/pathway/hsa/hsa01510.html（NDD的KEGG通路图）联系方式：kanehisa@kuicr.kyoto-u.ac.jp
Motivation: Neurodegenerative disorders (NDDs) are progressive and fatal disorders, which are commonly characterized by the intracellular or extracellular presence of abnormal protein aggregates. The identification and verification of proteins interacting with causative gene products are effective ways to understand their physiological and pathological functions. The objective of this research is to better understand common molecular pathogenic mechanisms in NDDs by employing protein-protein interaction networks, the domain characteristics commonly identified in NDDs and correlation among NDDs based on domain information.Results: By reviewing published literatures in PubMed, we created pathway maps in Kyoto Encyclopedia of Genes and Genomes (KEGG) for the protein-protein interactions in six NDDs: Alzheimer's disease ( AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), dentatorubral-pallidoluysian atrophy ( DRPLA) and prion disease ( PRION). We also collected data on 201 interacting proteins and 13 compounds with 282 interactions from the literature. We found 19 proteins common to these six NDDs. These common proteins were mainly involved in the apoptosis and MAPK signaling pathways. We expanded the interaction network by adding protein interaction data from the Human Protein Reference Database and gene expression data from the Human Gene Expression Index Database. We then carried out domain analysis on the extended network and found the characteristic domains, such as 14-3-3 protein, phosphotyrosine interaction domain and caspase domain, for the common proteins. Moreover, we found a relatively high correlation between AD, PD, HD and PRION, but not ALS or DRPLA, in terms of the protein domain distributions.Availability: http://www.genome.jp/kegg/pathway/hsa/hsa01510.html ( KEGG pathway maps for NDDs)Contact: kanehisa@kuicr.kyoto-u.ac.jp