认知相关基因的生化通路与蛋白质互作网络分析

目的用生物信息学的方法揭示认知相关基因所调控的生物过程及通路,构建认知基因的特异蛋白网络,并挖掘其主要功能。方法在GO、phenopedia、GLAD4U3个数据库中,收集认知相关的基因,进行基因本体分析、通路分析及通路串话分析;从人类蛋白互作网络中提取认知相关特异蛋白网络,并通过聚类分析找出重要功能模块。结果明确了126个认知相关基因,这些基因主要参与学习或记忆、神经发育等生物过程;多条与神经突触发育、信号转导、成瘾相关的通路参与认知过程,且各个通路之间存在紧密的串话作用。认知相关基因之间存在显著的互相作用关系(P<10^-16),相比背景基因具有更高节点度(P=1.39×10^-4)以及介数中心性(P=2.07×10^-5);聚类分析挖掘出胺转运调节、胆碱能突触传递和学习等重要功能模块。结论认知是一个非常复杂的过程,涉及多个具有关键功能的基因,如HTR3A、CHRNA6、BDNF等,基因间通过紧密互相作用,调控多个生物过程及通路,包括胆碱能突触,多巴胺能突触、血清素能突触等,这些通路彼此协同发挥功能。

Analysis of Biochemical Pathways and Protein Interaction Networks of Cognition-related Genes

Objective To reveal the biological processes and pathways regulated by cognition-related genes through bioinformatics methods,and to construct a specific protein network of cognition-related genes and explore its main functions.Methods Cognition-related genes were collected from GO,phenopedia and GLAD4U.Then gene ontology analysis and pathway analysis were performed to identify biological processes and pathways involved in cognition-related genes.A specific protein-protein interaction network of cognitive genes was extracted from the human protein-protein interaction network,and clustering analysis was used to identify the important functional modules.Results A total of 126 clear cognition-related genes involving in some biological processes related to learning or memory,neurodevelopment,etc.were obtained.Several pathways associated with neurodevelopment,signal transduction and addiction were involved in the cognitive process,and there were close crosstalk relationships among the enriched pathways.Meanwhile,there were significant interactions among cognition-related genes(P<10^-16),and cognition-related genes had significantly higher degree(P=1.39×10^-4)and betweenness centrality(P=2.07×10^-5)than background genes in human protein-protein interaction network.Several important functional modules were identified by cluster analysis,including amine transport regulations,cholinergic synaptic transmission and learning,etc.Conclusion Cognition is a very complex process involving multiple genes with key functions,such as HTR3A,CHRNA6,BDNF,etc.Multiple biological processes and pathways are regulated through the close interaction between genes,including cholinergic synapse,dopaminergic synapse,serotonergic synapse,etc.By closely interacting with each other,these pathways are regulated and function together.