Lin Chung-Yen, Chin Chia-Hao, Wu Hsin-Hung, Chen Shu-Hwa, Ho Chin-Wen, Ko Ming-Tat
Institute of Information Science, Academia Sinica, No. 128 Yan-Chiu-Yuan Rd., Sec. 2, Taipei 115, Taiwan.
Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W438-43. doi: 10.1093/nar/gkn257. Epub 2008 May 24.
One major task in the post-genome era is to reconstruct proteomic and genomic interacting networks using high-throughput experiment data. To identify essential nodes/hubs in these interactomes is a way to decipher the critical keys inside biochemical pathways or complex networks. These essential nodes/hubs may serve as potential drug-targets for developing novel therapy of human diseases, such as cancer or infectious disease caused by emerging pathogens. Hub Objects Analyzer (Hubba) is a web-based service for exploring important nodes in an interactome network generated from specific small- or large-scale experimental methods based on graph theory. Two characteristic analysis algorithms, Maximum Neighborhood Component (MNC) and Density of Maximum Neighborhood Component (DMNC) are developed for exploring and identifying hubs/essential nodes from interactome networks. Users can submit their own interaction data in PSI format (Proteomics Standards Initiative, version 2.5 and 1.0), tab format and tab with weight values. User will get an email notification of the calculation complete in minutes or hours, depending on the size of submitted dataset. Hubba result includes a rank given by a composite index, a manifest graph of network to show the relationship amid these hubs, and links for retrieving output files. This proposed method (DMNC || MNC) can be applied to discover some unrecognized hubs from previous dataset. For example, most of the Hubba high-ranked hubs (80% in top 10 hub list, and >70% in top 40 hub list) from the yeast protein interactome data (Y2H experiment) are reported as essential proteins. Since the analysis methods of Hubba are based on topology, it can also be used on other kinds of networks to explore the essential nodes, like networks in yeast, rat, mouse and human. The website of Hubba is freely available at http://hub.iis.sinica.edu.tw/Hubba.
后基因组时代的一项主要任务是利用高通量实验数据重建蛋白质组和基因组相互作用网络。识别这些相互作用组中的关键节点/枢纽是解读生化途径或复杂网络内部关键因素的一种方法。这些关键节点/枢纽可作为开发人类疾病(如癌症或由新出现病原体引起的传染病)新疗法的潜在药物靶点。枢纽对象分析器(Hubba)是一项基于网络的服务,用于基于图论探索由特定小规模或大规模实验方法生成的相互作用组网络中的重要节点。开发了两种特征分析算法,即最大邻域组件(MNC)和最大邻域组件密度(DMNC),用于从相互作用组网络中探索和识别枢纽/关键节点。用户可以提交PSI格式(蛋白质组学标准倡议,版本2.5和1.0)、表格格式以及带权重值的表格形式的自己的相互作用数据。根据提交数据集的大小,用户将在几分钟或几小时内收到计算完成的电子邮件通知。Hubba结果包括由综合指数给出的排名、显示这些枢纽之间关系的网络示意图以及用于检索输出文件的链接。这种提出的方法(DMNC || MNC)可应用于从先前的数据集中发现一些未被识别的枢纽。例如,酵母蛋白质相互作用组数据(酵母双杂交实验)中Hubba排名靠前的枢纽(前10个枢纽列表中80%,前40个枢纽列表中>70%)大多被报告为必需蛋白。由于Hubba的分析方法基于拓扑结构,它也可用于其他类型的网络来探索关键节点,如酵母、大鼠、小鼠和人类的网络。Hubba网站可在http://hub.iis.sinica.edu.tw/Hubba免费获取。