Identification of major depressive disorder disease-related genes and functional pathways based on system dynamic changes of network connectivity

Abstract

Objective : Major depressive disorder (MDD) is a neurologic disorder, involving complex abnormal biological functions and the neural network. In this study, we aimed to compare different network connectivity of pathological changes of brain tissues under different conditions, and dynamic analyze the biological pathways and genes significantly associated with disease progression, and further to predict potential drug targets. Methods : Datasets of mRNA expression profiles of samples of postmortem anterior cingulate cortex (ACC) and prefrontal cortex (PFC) from patients with MDD were downloaded from GEO database. We used a method based on system network analysis. Correlation networks based on co-expression were constructed. Topological properties of the networks were analyzed and compared. Results : Our results showed that the lesions of brain tissues in MDD patients were not synchronized and alterations of biological functions were not consistent either. ACC showed a greater degree of abnormality as compared to PFC suggesting a higher correlation with disease progression. We consequently analyzed the signaling pathways enriched by DEGs and further cross talk genes that bridge the multiple pathways were also identified. Through construction of the pathway-gene complex network, the genes and signaling pathways with top10 degrees were extracted, which are more likely to be the potential novel therapeutic targets. We also mined the drugbank database for the top10 cross talk genes to explore their drugable target potential. The results suggested that CACNA1A, PTDSS2 and CD19 differentially expressed in both ACC and PFC may correlate with depression progression or other cerebral nerve system related diseases, are more likely to become the new drug targets. Conclusion : Co-expression network and tissue comparing analysis are capable to identify MDD disease related signaling pathways and cross talk genes with potential to be novel drug targets.