致心律失常性右心室心肌病致病蛋白的挖掘  

Mining Arrhythmogenic Right Ventricular Cardiomyopathy Potential Disease Protein

作　　者：崔丹[1] 闫玉清[1] 李琬[2] 陈丽娜[2] 李为国 太京燮[2] 张良才[2] 宿滨[2] 李心玲[1] 

机构地区：[1]哈尔滨师范大学生命科学与技术学院,黑龙江哈尔滨150025 [2]哈尔滨医科大学生物信息科学与技术学院,黑龙江哈尔滨150081

出　　处：《现代生物医学进展》2012年第18期3425-3429,共5页Progress in Modern Biomedicine

基　　金：黑龙江省教育厅基金(12511271);黑龙江省自然科学基金(D200834)

摘　　要：目的:鉴定疾病蛋白对深入理解致心律失常性右心室心肌病(ARVC)致病机制至关重要。可以采用计算生物学的方法,在ARVC疾病相关网络中挖掘新的潜在的致病蛋白。方法:本文整合HPRD和BioGRID的蛋白质互作数据,获得了较为全面且真实可靠的蛋白质互作数据;通过结合文本挖掘和统计学检验筛选出ARVC种子蛋白,应用最近邻居扩增的方法,构建ARVC蛋白质互作网络(PPIN),并采用PRINCESS法则对网络中每对互作蛋白加权;最后,基于ARVC关联得分策略对网络中的每个蛋白质打分并排秩。结果:分析发现排秩前50的候选蛋白大都与ARVC关系密切,如PRKCA,CDH1,SMAD4,SMAD2,CDH5,CTNNA1,DSC1等在调节心肌收缩、细胞程序性死亡、心脏的发育过程及维持桥粒的完整性方面起重要作用。结论:我们提出的方法为鉴定与ARVC致病机制相关的新致病蛋白提供了有效的途径。Objective： Identification of disease proteins is important to understand the mechanism of Arrhythmogenic Right Ven- tricular Cardiomyopathy （ARVC）. Computational biological methods can be used to mine potential disease proteins in disease-related network. Methods： We integrated protein-protein interaction data from HPRD and BioGRID databases to obtain a more comprehensive and trustworthy protein-protein interaction data. The method of text mining combined with statistical tests was used to screen ARVC can- didate proteins. ARVC-Protein-Protein Interaction Network （PPIN） was built through the nearest-neighbor expansion method and weighted each protein pair in the network using PRINCESS. Then an ARVC-related score strategy was presented to rank each protein of the network. Results： Top 50 candidate proteins were analyzed, and most candidate proteins were closely associated with ARVC, such as PRKCA, CDH1, SMAD4, SMAD2, CDH5, CTNNA1, DSC1. They played an important role in regulating myocardial contractility, cell degeneration, heart development and maintaining the integrity of desmosomes. Conclusions： Our approach reported here provides new insights for the identification of disease genes, and will be helpful for the studies on the pathogenesis of ARVC in depth.

关 键 词：致心律失常性右心室心肌病 蛋白质互作网络 致病蛋白 

分 类 号：R541.7[医药卫生—心血管疾病] R542.2[医药卫生—内科学]