Integrated Analysis of Methylomic and Transcriptomic Data to Identify Potential Diagnostic Biomarkers for Major Depressive Disorder.

Major depressive disorder (MDD) is a mental illness with high incidence and complex etiology, that poses a serious threat to human health and increases the socioeconomic burden. Currently, high-accuracy biomarkers for MDD diagnosis are urgently needed. This paper aims to identify novel blood-based diagnostic biomarkers for MDD. Whole blood DNA methylation data and gene expression data from the Gene Expression Omnibus database are downloaded. Then, differentially expressed/methylated genes (DEGs/DMGs) are identified. In addition, we made a systematic analysis of the DNA methylation on 5'-C-phosphate-G-3' (CpGs) in all of the gene regions, as well as different gene regions, and then we defined a "dominant" region. Subsequently, integrated analysis is employed to identify the robust MDD-related blood biomarkers. Finally, a gene expression classifier and a methylation classifier are constructed using the random forest algorithm and the leave-one-out cross-validation method. Our results demonstrate that DEGs are mainly involved in the inflammatory response-associated pathways, while DMGs are primarily concentrated in the neurodevelopment- and neuroplasticity-associated pathways. Our integrated analysis identified 46 hypo-methylated and up-regulated (hypo-up) genes and 71 hyper-methylated and down-regulated (hyper-down) genes. One gene expression classifier and two DNA methylation classifiers, based on the CpGs in all of the regions or in the dominant regions are constructed. The gene expression classifier possessed the best predictive ability, followed by the DNA methylation classifiers, based on the CpGs in both the dominant regions and all of the regions. In summary, the integrated analysis of DNA methylation and gene expression has identified 46 hypo-up genes and 71 hyper-down genes, which could be used as diagnostic biomarkers for MDD.