Affection of Comt1 genetype on anxiety and nociceptive sensitivity: an Ego-network analysis approach

The aim of this study was to predict key genes and their relationships for anxiety and nociceptive sensitivity related to Comt1 genetype.

: The raw data of E-GEOD-20160 related to anxiety and nociceptive sensitivity were obtained. Pearson correlation coefficient of interaction in protein–protein interaction was calculated. Topological analysis was processed for protein– protein interaction network, and genes in this network were ranked based on their degrees. Ego genes were identified, and models were searched and refined. A total of 1000 randomized tests were processed for ego networks. The classification accuracy of each ego network was obtained in this process.

The interactions with genes in gene expression profiles were extracted, and protein–protein interaction was constructed. The protein–protein interaction included 4639 genes and 43,837 relationships. Differential co-expression network was constructed, and 74 ego genes were obtained. Thereinto, top five ego genes were ADCY2, GRM8, S1PR3, ADCY6, and ANXA1. After module searching and refinement, a total of 11 candidate modules were obtained, including module 14, module 51, and module 9. In addition, these 11 modules were confirmed to be with significance. Module 14 contained 10 genes, such as HRH3, DRD2, and CXCR3. Similarly, module 51 included six genes, such as HELZ2, NCOA3, and MED30.

Ego network analysis was a useful and comprehensive method for biomarkers screening. Several modules such as module 3 and module 36 were important subnetworks. Potential genes in these modules including ADCYs, GNAI1, DRD2, PNOC, CCR2, DRD2, and LPAR1 might be important genes in the research of anxiety and nociceptive sensitivity.