基于蛋白质互作网络挖掘自闭症谱系障碍的功能模块与核心基因  

Identification of Functional Modules and Hub Genes in Autism Spectrum Disorder Based on Protein-Protein Interaction Network Analysis

作　　者：许逸聪 胡婉雪 谢芹 赵洪波 唐欣 XU Yi-cong;HU Wan-xue;XIE Qin;ZHAO Hong-bo;TANG Xin(Yunnan Key Laboratory of Stem Cell and Regenerative Medicine,Institute of Molecular and Clinical Medicine;School of Rehabilitation,Kunming Medical University,Kunming 650500,Yunnan,China)

机构地区：[1]昆明医科大学分子临床医学研究院暨云南省干细胞和再生医学重点实验室,中国云南昆明650500 [2]昆明医科大学康复学院,中国云南昆明650500

出　　处：《生命科学研究》2020年第3期214-221,共8页Life Science Research

基　　金：云南省科技厅-昆明医科大学联合专项面上项目(2018FE001(-197));昆明医科大学百名中青年学术技术骨干项目(60118090114)。

摘　　要：自闭症谱系障碍(autism spectrum disorder,ASD)是一种具有高遗传性、临床异质性和生物复杂性的神经行为障碍类疾病。为挖掘ASD发生发展过程中的功能模块与核心基因,本文从自闭症谱系障碍疾病数据库获取ASD相关基因;利用STRING数据库构建ASD相关基因的蛋白质互作网络;通过MCODE算法对蛋白质互作网络进行模块分析并筛选核心基因;最后对各功能模块进行KEGG通路分析,根据富集到的通路类别评估功能模块之间的相互作用。结果显示,3个疾病基因数据库筛选出182个共有基因,构建的蛋白质互作网络包含171个节点和1041条边,其中NRXN1、GRIN2B、GRIN2A、DLG4、NLGN3、MECP2、CNTNAP2、BDNF、NLGN4X、FMR1等23个基因具有较高的连通度(degree)。从蛋白质互作网络中分析得到5个功能模块,包括68个核心基因。KEGG富集分析发现功能模块参与多个生物学通路,包括细胞黏附分子、钙离子通路、神经活性的配体-受体相互作用、多巴胺能神经突触等。分析结果提示,挖掘的ASD功能模块和核心基因大多集中在神经元活动、信号分子和信号传导等,且各模块相互作用共同影响ASD的发生发展。Autism spectrum disorder(ASD)is a neurobehavioral disorder with high heritability,clinical heterogeneity and biological complexity.It is necessary to identify functional modules and hub genes related to ASD.Herein,ASD related genes were obtained from disease-gene databases and imported into STRING database for protein-protein interaction(PPI)network construction.Then module analysis and hub gene se lection were performed by MCODE algorithm.Subsequently,KEGG pathway enrichment analysis of each functional module was performed for evaluating the interactions between the functional modules based on the enriched pathway categories.A total of 182 related genes were screened from disease-gene databases.These overlapped genes were translated into PPI network consisting of 171 nodes and 1041 edges,including NRXN1,GRIN2B,GRIN2A,DLG4,NLGN3,MECP2,CNTNAP2,BDNF,NLGN4X and FMR1 with higher degree.Five functional modules including 68 hub genes were extracted using MCODE algorithm.KEGG enrichment analysis of detected modules revealed that these modules are related to cell adhesion molecules,calcium signaling pathway,neuroactive ligand-receptor interaction and dopaminergic synapse.The results suggested that most of the ASD functional modules and hub genes are concentrated in neuronal activity,sig nal molecules and signaling transduction,and the interaction of each module affects the occurrence and de velopment of ASD.

关 键 词：自闭症谱系障碍(ASD) 蛋白质互作网络 功能模块 核心基因 

分 类 号：Q811.4[生物学—生物工程] R749.94[医药卫生—神经病学与精神病学]