摘要： 目的·采用加权基因共表达网络分析（weighted gene co-expression network analysis，WGCNA）探索抑郁症相关的差异基因模块及其枢纽基因，并对差异基因模块进行生物功能注释。方法·在之前对8例抑郁症患者及8名健康对照者（对照组）的外周血mRNA微阵列分析实验的基础上，应用
t检验筛选抑郁症患者与对照组的差异表达基因，通过R软件WGCNA包进行分析；当关联系数阈值设定为0.9时，参数
β=14，以此构建基因数据集的共表达网络。应用混合动态树切割方法切割网络产生基因模块。采用Pearson相关性检验评估基因模块和抑郁症之间的相关性，分别选取与抑郁症正相关性和负相关性最强的基因模块，并选择模块内连接性最强的前3个基因作为枢纽基因。最后利用GO功能富集分析和KEGG通路分析对2个模块进行功能注释。结果·从16个样品中获得4 125个差异表达基因，从中识别出9个基因模块，选择蓝色（blue）模块（
R=－0.91，
P=0.000）和青色（cyan）模块（
R=0.76，
P=0.000）进行后续研究。Blue模块的枢纽基因为
JAM2（junctional adhesion molecule 2）、
SCRN2（secernin 2）和
IGHV7-81（immunoglobulin heavy variable 7-81）；cyan模块的枢纽基因为
SCFD2（Sec1 family domain containing 2）、
NR5A2（nuclear receptor subfamily 5 group A member 2）和
KCNMA1（potassium calcium-activated channel subfamily M alpha 1）。生物功能注释发现，cyan模块的基因主要富集在胚胎发育、细胞生长、免疫及炎症等生物学过程，blue模块基因则主要在物质加工转运及感染等方面富集。结论·得到2个外周血mRNA基因模块和6个枢纽基因（
JAM2、SCRN2、IGHV7-81、SCFD2、NR5A2和
KCNMA1），可能与抑郁症显著相关；这2个基因模块可能在胚胎发育、免疫和炎症反应、物质加工转运等方面发挥作用。
关键词: 抑郁症, 加权基因共表达网络分析, 差异表达基因, 枢纽基因 Abstract: Objective·To explore the differential gene modules and hub genes of major depressive disorder (MDD) by weighted gene co-expression network analysis (WGCNA), and annotate the biological functions of the differential gene modules.
Methods·Based on the previous experiment of peripheral blood mRNA microarray analysis of 8 MDD patients and 8 healthy controls (control group), t-test statistical method was used to screen the differentially expressed genes between MDD and the control group. WGCNA package in R software was used to analyze the weighted gene co-expression network. The correlation coefficient threshold was set to 0.9 with β =14 to construct the co-expression network of the gene dataset. The hybrid dynamic tree cutting method was used to cut the network to generate gene modules. Pearson correlation test was used to evaluate the correlation between gene modules and MDD. The gene modules with the strongest positive correlation and the strongest negative correlation with depression were selected respectively, and the top three genes with the highest connectivity in the modules were defined as hub genes. Finally, GO functional enrichment analysis and KEGG pathway analysis were used to annotate the functions of the two modules.
Results·A total of 4 125 differentially expressed genes were obtained from 16 samples, and 9 gene modules were identified. The blue module (R=-0.91, P=0.000) and the cyan module (R=0.76, P=0.000) were selected for further study. The hub genes of blue module were JAM2 (junctional adhesion molecule 2), SCRN2 (secernin 2) and IGHV7-81 (immunoglobulin heavy variable 7-81). The hub genes of cyan module were SCFD2 (Sec1 family domain containing 2), NR5A2 (nuclear receptor subfamily 5 group A member 2) and KCNMA1 (potassium calcium-activated channel subfamily M alpha 1). It was found in the annotation of biological function that the genes of the cyan module were mainly enriched in the embryo development, cell growth and immune and inflammatory response, while the genes of the blue module were mainly enriched in material processing and transport and infection.
Conclusion·Two peripheral blood mRNA gene modules and six hub genes (JAM2, SCRN2, IGHV7-81, SCFD2, NR5A2 and KCNMA1) may be significantly associated with MDD. These two gene modules may play a role in the embryonic development, immune and inflammatory response, and material processing and transportation.
Key words: major depressive disorder (MDD), weighted gene co-expression network analysis (WGCNA), differentially expressed gene (DEG), hub gene PDF全文下载地址:
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